Non‐surgical adjunctive interventions for accelerating tooth movement in patients undergoing orthodontic treatment

Abstract

Background

Deviation from a normal bite can be defined as malocclusion. Orthodontic treatment takes 20 months on average to correct malocclusion. Accelerating the rate of tooth movement may help to reduce the duration of orthodontic treatment and associated unwanted effects including orthodontically induced inflammatory root resorption (OIIRR), demineralisation and reduced patient motivation and compliance. Several non‐surgical adjuncts have been advocated with the aim of accelerating the rate of orthodontic tooth movement (OTM).        

Objectives

To assess the effect of non‐surgical adjunctive interventions on the rate of orthodontic tooth movement and the overall duration of treatment.

Search methods

An information specialist searched five bibliographic databases up to 6 September 2022 and used additional search methods to identify published, unpublished and ongoing studies.

Selection criteria

We included randomised controlled trials (RCTs) of people receiving orthodontic treatment using fixed or removable appliances along with non‐surgical adjunctive interventions to accelerate tooth movement. We excluded split‐mouth studies and studies that involved people who were treated with orthognathic surgery, or who had cleft lip or palate, or other craniofacial syndromes or deformities.

Data collection and analysis

Two review authors were responsible for study selection, risk of bias assessment and data extraction; they carried out these tasks independently. Disagreements were resolved by discussion amongst the review team to reach consensus. 

Main results

We included 23 studies, none of which were rated as low risk of bias overall. We categorised the included studies as testing light vibrational forces or photobiomodulation, the latter including low level laser therapy and light emitting diode. The studies assessed non‐surgical interventions added to fixed or removable orthodontic appliances compared to treatment without the adjunct. A total of 1027 participants (children and adults) were recruited with loss to follow‐up ranging from 0% to 27% of the original samples. 

Certainty of the evidence

For all comparisons and outcomes presented below, the certainty of the evidence is low to very low.

Light vibrational forces 

Eleven studies assessed how applying light vibrational forces (LVF) affected orthodontic tooth movement (OTM). There was no evidence of a difference between the intervention and control groups for duration of orthodontic treatment (MD ‐0.61 months, 95% confidence interval (CI) ‐2.44 to 1.22; 2 studies, 77 participants); total number of orthodontic appliance adjustment visits (MD ‐0.32 visits, 95% CI ‐1.69 to 1.05; 2 studies, 77 participants); orthodontic tooth movement during the early alignment stage (reduction of lower incisor irregularity (LII)) at 4‐6 weeks (MD 0.12 mm, 95% CI ‐1.77 to 2.01; 3 studies, 144 participants), or 10‐16 weeks (MD ‐0.18 mm, 95% CI ‐1.20 to 0.83; 4 studies, 175 participants); rate of canine distalisation (MD ‐0.01 mm/month, 95% CI ‐0.20 to 0.18; 2 studies, 40 participants); or rate of OTM during en masse space closure (MD 0.10 mm per month, 95% CI ‐0.08 to 0.29; 2 studies, 81 participants). No evidence of a difference was found between LVF and control groups in rate of OTM when using removable orthodontic aligners. Nor did the studies show evidence of a difference between groups for our secondary outcomes, including patient perception of pain, patient‐reported need for analgesics at different stages of treatment and harms or side effects. 

Photobiomodulation

Ten studies assessed the effect of applying low level laser therapy (LLLT) on rate of OTM. We found that participants in the LLLT group had a statistically significantly shorter length of time for the teeth to align in the early stages of treatment (MD ‐50 days, 95% CI ‐58 to ‐42; 2 studies, 62 participants) and required fewer appointments (‐2.3, 95% CI ‐2.5 to ‐2.0; 2 studies, 125 participants). There was no evidence of a difference between the LLLT and control groups in OTM when assessed as percentage reduction in LII in the first month of alignment (1.63%, 95% CI ‐2.60 to 5.86; 2 studies, 56 participants) or in the second month (percentage reduction MD 3.75%, 95% CI ‐1.74 to 9.24; 2 studies, 56 participants). However, LLLT resulted in an increase in OTM during the space closure stage in the maxillary arch (MD 0.18 mm/month, 95% CI 0.05 to 0.33; 1 study; 65 participants; very low level of certainty) and the mandibular arch (right side MD 0.16 mm/month, 95% CI 0.12 to 0.19; 1 study; 65 participants). In addition, LLLT resulted in an increased  rate of OTM during maxillary canine retraction (MD 0.01 mm/month, 95% CI 0 to 0.02; 1 study, 37 participants). These  findings were not clinically significant. The studies showed no evidence of a difference between groups for our secondary outcomes, including OIIRR, periodontal health and patient perception of pain at early stages of treatment.

Two studies assessed the influence of applying light‐emitting diode (LED) on OTM. Participants in the LED group required a significantly shorter time to align the mandibular arch compared to the control group (MD ‐24.50 days, 95% CI ‐42.45 to ‐6.55, 1 study, 34 participants). There is no evidence that LED application increased the rate of OTM during maxillary canine retraction (MD 0.01 mm/month, 95% CI 0 to 0.02; P = 0.28; 1 study, 39 participants ). In terms of secondary outcomes, one study assessed patient perception of pain and found no evidence of a difference between groups.  

Authors' conclusions

The evidence from randomised controlled trials concerning the effectiveness of non‐surgical interventions to accelerate orthodontic treatment is of low to very low certainty. It suggests that there is no additional benefit of light vibrational forces or photobiomodulation for reducing the duration of orthodontic treatment. Although there may be a limited benefit from photobiomodulation application for accelerating discrete treatment phases, these results have to be interpreted with caution due to their questionable clinical significance. Further well‐designed, rigorous RCTs with longer follow‐up periods spanning from start to completion of orthodontic treatment are required to determine whether non‐surgical interventions may reduce the duration of orthodontic treatment by a clinically significant amount, with minimal adverse effects.

Plain language summary

Additional, non‐surgical treatments for accelerating tooth movement in dental patients being treated with fixed braces

Review question
Do additional non‐surgical procedures that claim to accelerate orthodontic tooth movement reduce the overall length of orthodontic treatment?

Background
Throughout the world, orthodontic treatment is used to correct the position of teeth in adolescents and adults when they experience problems with their teeth and bite. Orthodontic appliances can vary in type, and include fixed braces (made up of brackets glued to the teeth and then connected by wires) and removable appliances, e.g. clear aligners, which are a set of clear plastic removable gum shields that fit closely over the teeth. Depending on the tooth and bite problem, the length of time for orthodontic treatment may range from several months to several years. However, most full orthodontic treatments take typically around 20 months. Orthodontic treatment is known to improve how a smile looks, which in turn has a positive impact on patients; however, orthodontic treatment can carry some unwanted risks, such as tooth decay and shortening of tooth roots. Accelerating the rate of tooth movement may help to reduce the length of time needed for a course of treatment and may reduce the unwanted effects of orthodontic treatment that can sometimes occur. Several methods, including surgical and non‐surgical treatments, have been suggested to accelerate orthodontic tooth movement. The evidence relating to non‐surgical treatments to accelerate orthodontic tooth movement is assessed in this review.

Authors for Cochrane Oral Health carried out this update of the systematic review of existing studies. The evidence on which it is based is current up to September 2022.

Study characteristics

We included 23 studies involving a total of 1027 participants, both males and females, and children and adults. These investigated light vibrational force appliances, low level laser therapy and light‐emitting diode (LED) therapy as extras to orthodontic treatment in both private practice and university hospital settings. The trials evaluated different aspects of orthodontic tooth movement and side effects. In the studies, participants were being treated either with fixed orthodontic appliances or orthodontic removable aligners. The participants in all studies had dental (tooth) crowding in one or both arches. Some studies included participants requiring tooth extractions for relief of dental crowding and correction of their bite with space closure, while other studies included participants who did not require dental extractions. The percentage of participants lost to follow‐up in the studies included in this review ranged from 0% to 27% of the original samples.

The studies evaluated seven outcomes: duration of orthodontic treatment; number of appointments required to adjust orthodontic appliance, the rate of orthodontic tooth movement at different stages, patient perception of pain and discomfort, patient reported need for painkillers, and unwanted side effects. There were substantial differences between some of the studies; however, it was possible to combine the results of some studies for the light vibrational forces and low level laser therapy. 

Key results

There is low‐certainty evidence to suggest that applying light vibrational forces during orthodontic treatment (fixed or removable appliances) has no significant advantage for any of the outcomes assessed. 

There is very low‐certainty evidence to suggest that applying low level laser and LED therapy can reduce the duration of the early stage of orthodontic fixed brace treatment (alignment), but it is difficult to estimate the impact of this outcome on the full comprehensive orthodontic treatment duration.

Conclusion

From the limited evidence available, we did not find a benefit from the use of light vibrational forces or photobiomodulation for the reduction of orthodontic treatment duration. However, there could be a potential benefit from photobiomodulation to reduce the length of the early stage of orthodontic treatment only and increase the speed of orthodontic tooth movement; it is important to realise that the results from discrete phases do not necessarily have similar impact on the full orthodontic treatment duration. Further well‐designed studies with longer follow‐up are needed.

Certainty of the evidence

Our certainty about the evidence is low to very low.

Summary of findings

Summary of findings 1. Summary of findings 1: adjunctive light vibrational forces versus conventional orthodontic treatment.

Light vibrational forces as an adjunctive to conventional orthodontic treatment compared with conventional orthodontic treatment
Population: adolescents and adults with malocclusion undergoing orthodontic treatment Settings: teaching university hospitals and private practice Intervention:  orthodontic appliance treatment with vibrational light forces Comparison: conventional orthodontic appliance treatment
Outcomes	Anticipated absolute effects (95% CI)		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Absolute effect in control	Mean difference (MD) with
	Conventional orthodontic treatment	Non‐surgical adjunctive intervention
Duration of orthodontic treatment	Mean duration ranged  across groups from 19.7 to 20.71 months	Mean duration was 0.61 months fewer (2.44 fewer to 1.22 more)	‐	77 participants (2 RCTs)	⊕⊕⊝⊝ low 1	There was no evidence to suggest that LVF can either increase or decrease the total duration of orthodontic treatment.
Total number of orthodontic appliance adjustment appointments during treatment	Mean number of visits ranged across groups from 12.92 to 14.12	Mean number of visits was 0.32 less (1.05 fewer to 1.69 more)		77 participants (2 RCTs)	⊕⊕⊝⊝ low 2	There was no evidence to suggest that LVF can either increase or decrease the total number of appointments required for orthodontic appliance adjustment.
Orthodontic tooth movement (OTM) during alignment stage During full alignment stage (reduction in Little Irregularity Index (LII) in mm)	Mean reduction in LII score was 8.6 mm	Mean reduction in LII score was 0.20 mm less (7.02 less to 6.62 more)	‐	54 participants (1 RCT)	⊕⊕⊝⊝ low 3	There was no evidence to suggest that OTM during the alignment stage was either increased or decreased in the LVF group compared to the control.    OTM also assessed at other time points during alignment stage: at first 4‐6 weeks (3 RCTs; 144 participants) mean reduction in LII 0.12 mm more (1.77 less to 2.01 more); at 10‐16 weeks from the start of treatment (4 RCTs; 175 participants) mean reduction in LII score 0.18 mm less (1.20 less to 0.83 more).
Orthodontic tooth movement (OTM) during space closure stage (mm/month) During en masse space closure (maxillary and mandibular arch combined)	Mean rate of tooth movement ranged from 0.76 to 1.3 mm/month	Mean rate of space closure was 0.10 mm/month higher (0.08 lower to 0.29 higher)	‐	81 participants (2 RCTs)	⊕⊕⊝⊝ low4	There was no evidence to suggest that LVF can increase or decrease OTM during the space closure stage.     When assessed in the maxillary or mandibular arch only, there was also no evidence to suggest that LVF can increase or decrease OTM during the space closure stage (1 RCT; 40 and 41 participants, respectively). Likewise, when assessed through canine distalisation (2 RCTs, 40 participants).
Patient perception of pain and discomfort using VAS 0 to 100 mm Immediately after ligation of initial archwire	Mean pain and discomfort score in the control groups ranged from 8.1 to 28.27 mm	Mean pain and discomfort score was 2.56 higher (2.35 lower to 7.47 higher)	‐	153 participants (3 RCTs)	⊕⊕⊝⊝ low5	There was no evidence to suggest that LVF can increase or decrease patient's perception of pain following ligation of the initial aligning archwire.   Patient's perception of pain was assessed after the ligation of the first aligning arch wire at several time points: 4‐8 hours, 1 day, 3 days and  7 days (3 RCTs; 153 participants). There was no evidence that pain perception was greater or lower in the LVF group compared to the control group.     Pain perception after fitting the second aligning archwire was assessed by one study (Woodhouse 2015) (53 participants). There was no evidence that pain perception was greater or lower in the LVF group compared to the control group, except after 1 day where the pain perception was higher in the LVF group (MD 18.66 mm, 95% CI 3.41 to 33.91).
Patient‐reported need for analgesics During first week of the initial aligning archwire	Percentage of patients who reported need for analgesics in control group was 76.08%	Percentage was lower in intervention groups by 7.59%	OR 1.64  (lower 0.60 and higher 4.53)	76 participants (2 RCTs)	⊕⊕⊝⊝ low 6	There was no evidence to suggest that the patient‐reported need for analgesics following fitting the initial aligning archwire was greater or lower in the LVF group compared to the control group.    The patient‐reported need for analgesics was assessed after fitting the second archwire by one study (Woodhouse 2015) (53 participants) and was not greater or lower in the LVF group compared to the control group (OR 1.01, 95% CI ‐0.32 to 3.20).
Harms and side effects: OIIRR	Mean amount of OIIRR in control group was 1 mm (95% CI  0.61 to 1.38)	Mean amount of OIIRR in intervention groups was 0.09 mm higher (95% CI ‐0.35 to 0.53)		50 participants (1 RCT)	⊕⊕⊝⊝ low 7	There was no evidence to suggest that OIIRR was reduced, or increased, due to the use of LVF when compared to the control group.
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; LED: light‐emitting diode; LII: Little's irregularity index; LLLT: low level laser therapy; mm: millimetres; OTM: orthodontic tooth movement; OIIRR: orthodontically induced inflammatory root resorption; RR: risk ratio; VAS: visual analogue scale
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

¹ Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level for imprecision of evidence due to small sample size. 

² Downgraded one level for limitation in design and implementation due to overall high risk of bias. Also downgraded one level for imprecision of evidence due to small sample size. 

³ Downgraded two levels for imprecision of evidence due to small sample size and single study involving only mandibular arch with extraction treatment plan. Although the study was rated as unclear risk of reporting bias, this does not have a direct impact on this outcome. 

⁴ Downgraded one level for limitation in design and implementation due to overall high risk of bias. Also downgraded one level for imprecision of evidence due to inconsistency as the space closure for both the maxillary and mandibular arch were combined. 

⁵ Downgraded one level for limitation in design and implementation due to 2 studies out of 3 at high risk of bias. Downgraded one level for imprecision

⁶ Downgraded one level for limitation in design and implementation due to one study rated as high risk of bias.  Downgraded one level for imprecision of evidence due to wide confidence intervals. Also downgraded one level for indirectness due to short duration period assessed which does not represent the full treatment duration (surrogate results).

⁷ Downgraded one level for imprecision due to small sample size and single study rated unclear risk of bias. Also downgraded one level for indirectness due to short duration period assessed which does not represent the full treatment duration (surrogate results). 

Summary of findings 2. Summary of findings 2: adjunctive low level laser therapy versus conventional orthodontic treatment.

Low level laser therapy as an adjunctive intervention to conventional orthodontic treatment compared with conventional orthodontic treatment
Population: adolescents and adults with malocclusion undergoing orthodontic treatment Settings: teaching university hospitals Intervention: LLLT as an adjunctive intervention to conventional orthodontic treatment Comparison: conventional orthodontic treatment
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Experimental
Duration of orthodontic treatment during alignment stage only Alignment duration from start of orthodontic treatment until end of alignment stage	Mean duration ranged from 109.23 to 284.1 days	Mean duration was 48.87 days fewer (56.48 fewer to 41.26 fewer)		92 (3 RCTs)	⊕⊝⊝⊝ very low1	There was very low‐certainty evidence to suggest that the duration of the orthodontic alignment stage was reduced due to the use of LLLT when compared to the control group.
Total number of orthodontic appliance adjustment appointments required during treatment: alignment stage only	Median number of visits was 9.5 (lower 6.7 to higher 7.2)	Median number of visits was 2.5 fewer ( 2.52  fewer to fewer 1.97 fewer)		36 (1 RCT)	⊕⊝⊝⊝ very low2	There was very low‐certainty evidence to suggest that the total number of orthodontic appliance adjustment visits required during alignment stage was reduced due to the use of LLLT when compared to the control group.
Orthodontic tooth movement (OTM) during alignment stage (percentage reduction in LII in mm) During first 4 weeks of alignment stage	Mean reduction in LII ranged from 41.40% to 48.85%	Mean percentage reduction in LII was 1.63% greater (2.60 less to 5.86 greater)	‐	56 (2 RCTs)	⊕⊝⊝⊝ very low3	There was no evidence that OTM during the first 4 weeks of the alignment stage was either increased or decreased in the LLLT group compared to the control.    OTM was assessed at different time points by the same studies during the alignment stage: at first 8 weeks (2 RCTs; 56 participants) mean percentage reduction in LII  (mm) in the LLLT group was 3.75% greater (‐1.74 less to 9.24 greater) than in the control group.
Orthodontic tooth movement (OTM) during space closure stage mm/month  (maxillary arch)	Mean rate of space closure ranged from 0.48 to 0.50 mm/month	Mean rate of OTM was 0.18 higher (0.10  greater to 0.26 greater)		45 (1 RCT)	⊕⊝⊝⊝ very low4	There was very low‐certainty evidence to suggest that rate of OTM during space closure stage in the maxillary arch was increased due to the use of LLLT when compared to the control group.    OTM was assessed in the mandibular arch by the same study (Lalnunpuii 2020) during the space closure stage:  mean rate of space closure in the LLLT  was 0.16 mm/months greater mm/month ( 0.13 to greater 0.19). There was very low certainty evidence to suggest that rate of OTM during space closure stage in the mandibular arch was increased, due to the use of LLLT when compared to the control group   OTM was assessed during canine distalization/space closure Farhadian 2021 (1 RCTs; 37 participants). The mean rate of OTM was 0.01 mm/day higher (0 greater to 0.02 greater). There was insufficent evidence to suggest that LLLT can increased or decrease the rate of OTM  during canine distalisation/space closure stage.
Patient perception of pain and discomfort using VAS 0 to 100 mm	Mean pain and discomfort score in the control groups was 3.5  mm	Mean pain and discomfort score was 0.4 mm lower (‐1.87 lower to 1.07 higher)		37 (1 RCT)	⊕⊝⊝⊝ very low5	There was insufficent evidence to suggest that LLLT can increase or decrease patient's perception of pain during fixed orthodontic apppliance treatment.   Alam 2019; Ghaffer 2022 (high risk of bias) both assessed pain and discomfort using VAS during the early 7 days with the initial aligning archwires.  Ghaffer 2022 reporetd no increase or decrease in pain pereception except in the 5th day where the pain was reduced in the laser group.    Alam 2019 using a mix of  different types of orthodontic bracket systems (self ligating and conventional ligation) with reported reducecd pain score at several time points, mainly in combinatioin with self‐ligating bracket system.
Patient‐reported need for analgesics	Not reported
Harms and side effects	Not reported
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; LII: Little's irregularity index; LLLT: low level laser therapy; mm: millimetres; OTM: orthodontic tooth movement; RR: risk ratio; VAS: visual analogue scale
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

¹ Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level for imprecision of evidence due to wide confidence intervals with high heterogenity; also clinical heterogeneity among included studies resulted from different LLLT devices used. Downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results). 

² Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level for imprecision of evidence due to single study. Downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results).  

³ Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level for imprecision of evidence due to small sample. Downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results).

⁴ Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level for imprecision of evidence due to small sample. Downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results).

⁵ Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level for imprecision of evidence due to small sample. Downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results).

Summary of findings 3. Summary of findings 3: adjunctive light emitting diode versus conventional orthodontic treatment.

Light emitting diode as an adjunctive intervention to conventional orthodontic treatment compared with conventional orthodontic treatment
Population: adolescents and adults with malocclusion undergoing orthodontic treatment Settings: teaching university hospitals Intervention: LED as an adjunctive intervention to conventional orthodontic treatement Comparison: conventional orthodontic treatment
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Experimental
Duration of orthodontic treatment: alignment stage only Alignment duration from start of orthodontic treatment until end of alignment stage	Mean duration of orthodontic alignment stage was 87.8 days	Mean duration was 24.5 days fewer (6.55 fewer to 42.45 fewer)	‐	34 participants (1 RCT)	⊕⊝⊝⊝ very low1	There is very low‐certainty evidence to suggest that the duration of the orthodontic alignment stage was reduced due to the use of LED when compared to the control group.
Total number of orthodontic appliance adjustment appointments required during treatment stage	Not reported
Orthodontic tooth movement (OTM) during alignment stage	Not reported
Orthodontic tooth movement (OTM) during space closure stage mm/month  (canine distalisation)	Mean rate of canine distalisation was 0.023 mm/day	Mean rate of OTM was 0.006 mm/day higher (0 lower to 0.02 higher)	‐	39 (1 RCT)	⊕⊝⊝⊝ very low2	There is very low‐certainty evidence to suggest that the rate of OTM during canine distalisation/space closure stage in the maxillary arch was increased due to the use of LED when compared to the control group.    One study (Farhadian 2021) found LED increases the OTM, but difference was not clinically significant.
Patient perception of pain and discomfort using VAS 0 to 100 mm	Mean pain and discomfort score in the control groups was 3.5 mm	Mean pain and discomfort score was 0.80  mm lower (‐2.20 lower to  0.62 higher)	‐	39 (1 RCT)	⊕⊝⊝⊝ very low3	There was insufficent evidence to suggest that LED can increase or decrease patient's perception of pain during fixed orthodontic apppliance treatment. One study (Farhadian 2021)
Patient‐reported need for analgesics	Not reported
Harms and side effects	Not reported
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; LED: light‐emitting diode; LII: Little's irregularity index; mm: millimetres; OTM: orthodontic tooth movement; RR: risk ratio; VAS: visual analogue scale
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

¹Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level as single study. Also downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results). 

²Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level as single study. Also downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results). 

³Downgraded one level for limitation in design and implementation due to overall high risk of bias. Downgraded one level as single study. Also downgraded one level for indirectness due to short duration period assessed, which does not represent the full treatment duration (surrogate results). 

Background

Description of the condition

 Discrepancies in the arrangement of the teeth and the bite are called malocclusion (Andrews 1972). It is a common dental problem with a range of prevalence amongst different ethnic populations, with more than a quarter of adolescents classified as being in need of orthodontic treatment (Migale 2009; Mtaya 2009; Tausche 2004). Malocclusion can cause aesthetic and functional problems, which can lead to negative impacts on an individual’s emotional and social well‐being (Dimberg 2015). This is normally corrected using orthodontic treatment, which aims for dentoalveolar and/or orthopaedic outcomes using fixed or removable appliances, or both. In the current review the focus will be on dentoalveolar orthodontic tooth movement (OTM). 

There are clear benefits to patients of effective orthodontic treatment accomplished by delivering the planned treatment goals over the shortest time possible with high levels of patient satisfaction, minimal biological side effects and low financial cost. The duration of comprehensive orthodontic treatment may range from several months to several years, with an average treatment duration of approximately 20 months reported in a recent systematic review (Tsichlaki 2016). This can be extended for patients with a severe malocclusion. Reducing treatment duration can limit the risk of undesirable effects (e.g. root shortening or demineralisation) and associated cost, which can increase patient satisfaction (Riedmann 1999; Segal 2004).

Many factors can influence the duration of orthodontic treatment, including both patient‐related and treatment‐related factors (Fisher 2010; Mavreas 2008). Several conventional treatment modalities have been suggested aiming to reduce the duration of orthodontic treatment including brackets design and archwires however with no sound evidence to support those claims (Germec 2008; Maizeray 2021; Sebastian 2012; Yassir 2019). Similarly, in the last few decades, alternative techniques have been developed aiming to reduce treatment duration by accelerating the rate of tooth movement. These alternative techniques include surgical interventions (Fleming 2015) such as surgical corticotomy and non‐surgical interventions such as low level energy laser therapy and light vibrational forces (Caccianiga 2017; Miles 2016; Nahas 2017).

Description of the intervention

The proposed non‐surgical adjunctive interventions to accelerate orthodontic tooth movement include:

• Low energy laser radiation directed to the mucosa of the targeted teeth;

• Light vibrational forces (LVF) using an electrical appliance fitted into the orthodontic appliance or applied to the teeth;

• Light‐emitting diode LED

• Pulsed electromagnetic waves using integrated circuits placed in an oral appliance;

• Chewing gum or muscle exercise; and

• Novel methods as they are described by authors.

These interventions are used during conventional orthodontic appliance treatment, and are undertaken by the clinician in a clinical setting during additional scheduled visits (e.g. low energy laser radiation), or can be fitted in an intra‐oral or extra‐oral appliance and used by the patient on a daily or weekly basis following the clinician's prescription (e.g. pulsed electromagnetic waves and intermittent electrical vibration).

How the intervention might work

Orthodontic tooth movement occurs due to a sterile inflammatory process that results in bone resorption and deposition, which is known as bone remodelling (Zainal 2011). Bone cells (osteoclasts and osteoblasts) responsible for remodelling are the main target of non‐surgical interventions for accelerating tooth movement through upregulation of the inflammation process. This is because it has been proposed that such interventions can act as a bio‐stimulus to increase the activity of bone cells (Tortamano 2009). The Photobiomodulation has a biostimulatory effect which stimulates remodelling cells by the production of ATP and activation of cytochrome C, via RANK/RANKL and the macrophage colony‐stimulating factor and its receptor expression (Nimeri 2013 ). The light vibrational forces work according to the bioelectrical potential theory which originated from the bone bending theory in orthodontic tooth movement (Zainal 2011). The increased bone remodelling rate can increase the rate of tooth movement, which may lead to a reduction in the overall duration of orthodontic treatment.

Why it is important to do this review

Duration of treatment is an important aspect of successful and effective orthodontic treatment. Comprehensive orthodontic treatment typically takes nearly two years to complete and can be influenced by different factors, including patient‐related and treatment‐related aspects. Reduction in the duration of orthodontic treatment can reduce the exposure of patients to risks associated with treatment and related cost, and can increase patient satisfaction. Increased orthodontic treatment duration can increase the risk of the severity of OIIRR and demineralisation (Weltman 2010). In addition, increased treatment duration can lead to lack of patient's motivation and compliance with treatment (Fleming 2007).

This systematic review assessed the available evidence for the effect of non‐surgical adjunctive interventions on the reduction of orthodontic treatment duration by accelerating orthodontic tooth movement. However, the acceleration of orthodontic treatment during a short phase of treatment does not necessarily have a significant influence on the overall treatment duration which is the primary outcome of this review. In addition, the effect on treatment outcome, biological side effects and patient perception of treatment were evaluated. This will provide the orthodontic clinician with evidence about the effectiveness and safety of non‐surgical adjunctive interventions for accelerating orthodontic tooth movement.

Several systematic reviews have been published in the last few years with different study inclusion criteria, which has led to various conclusions. The first version of this review was originally published in 2015 and the current review is an update due to the increased relevant published studies in the last five years that necessitate assessment of the new evidence. 

Objectives

To assess the influence of non‐surgical adjunctive interventions for accelerating the rate of orthodontic tooth movement on the effectiveness of orthodontic treatment including treatment duration, treatment outcome, patient centred outcomes and side effects.  

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs), irrespective of publication status or language of publication. The split‐mouth study design was determined to be inappropriate for this type of investigation. This is because this type of study design may introduce 'carry‐across effects', which potentially allow interventions to have effects on experimental units other than those to which they were assigned. There was no restriction in the length of follow‐up.

Types of participants

We included studies involving individuals, of any age, receiving orthodontic treatment with fixed or removable orthodontic appliances that incorporated the adjunctive use of non‐surgical interventions to accelerate tooth movement. We excluded studies that included patients who were treated with orthognathic surgery, participants with cleft lip or palate, or with other craniofacial syndromes or deformities, as these patients would routinely have a combination of orthodontic and surgical treatment, which can influence the outcome, duration and side effects of the treatment.

Types of interventions

• Active interventions: any form of fixed or removable orthodontic appliance treatment incorporating the use of non‐surgical adjunctive interventions to accelerate orthodontic tooth movement

• Control: any form of fixed or removable orthodontic appliance treatment without the use of non‐surgical adjunctive interventions to accelerate orthodontic tooth movement or with the use of a different type of non‐surgical adjunctive intervention to accelerate orthodontic tooth movement

Types of outcome measures

Primary and secondary outcomes 

Primary outcomes

• Duration of active orthodontic treatment from the day the active appliance is fitted until it is removed at the end of active treatment.  

Secondary outcomes

• The number of visits required for activation of orthodontic appliance during active treatment (scheduled and unscheduled)

• Rate of reduction in the severity of dental arch malalignment through treatment using validated indices, e.g. Little's irregularity index (LII).

• Rate of orthodontic tooth movement (OTM) determined by millimetres of tooth movement per week or month.

• Improvement in occlusion, as judged using a validated index e.g. Peer Assessment Rating (PAR), recorded at the completion of active orthodontic treatment

• Patient‐centred outcomes: impact of fixed or removable orthodontic appliances and the adjunctive interventions on daily life, quality of life and pain experience

• Harms arising during the course of orthodontic treatment including periodontal problems, anchorage loss, and iatrogenic damage to teeth (e.g. caries or decalcification, root resorption) including any additional adverse events arising from the adjunctive intervention.

• Cost of treatment including the additional costs in terms of time and other resources in administering the additional intervention.

We did not include studies had measured only patient‐reported outcomes, harms or costs; studies had to measure some aspect of tooth movement.

Search methods for identification of studies

Electronic searches

Cochrane Oral Health’s Information Specialist conducted systematic searches in the following databases for randomised controlled trials and controlled clinical trials. There were no language, publication year or publication status restrictions:

• Cochrane Oral Health’s Trials Register (searched 6 September 2022) (Appendix 1);

• Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 8) in the Cochrane Library (searched 6 September 2022) (Appendix 2);

• MEDLINE Ovid (1946 to 6 September 2022) (Appendix 3);

• Embase Ovid (1980 to 6 September 2022) (Appendix 4);

• LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; from 1982 to 6 September 2022) (Appendix 5).

Subject strategies were modelled on the search strategy designed for MEDLINE Ovid. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategies designed by Cochrane for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions, Version 6.1 (Lefebvre 2022)).

Searching other resources

The following trial registries were searched for ongoing studies:

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 6 September 2022) (Appendix 6);

• World Health Organisation International Clinical Trials Registry Platform (apps.who.int/trialsearch; searched 8 September 2022) (Appendix 6).

The metaRegister of controlled trials (mRCT) was searched in November 2014, however this resource is no longer available. The search strategy is reported in Appendix 6.

We examined the reference lists of relevant articles and contacted the investigators of included studies by electronic mail to ask for details of additional published and unpublished trials if needed.

We checked that none of the included studies in this review were retracted due to error or fraud.

We did not perform a separate search for adverse effects of interventions used, we considered adverse effects described in included studies only.

Data collection and analysis

Selection of studies

Two review authors (AE and PSF) independently assessed the titles and abstracts of studies identified by the searches. The search was designed to be sensitive and include controlled clinical trials, these were filtered out early in the selection process if they were not randomised. Full copies were obtained of all relevant and potentially relevant studies, and for studies that appeared to meet the inclusion criteria but for which there were insufficient data in the title and abstract to make a clear decision. The full‐text papers were independently assessed by two review authors (AE and DB). Any disagreement on the eligibility of an included study was resolved through discussion and consensus. Consulting with a third review author if needed. From this group of full‐text papers, we recorded the studies not meeting the inclusion criteria, with reasons for exclusion, in the Characteristics of excluded studies section of the review.

Data extraction and management

Two review authors (AE and GM) independently extracted data. We used data extraction forms recording the year of publication, country of origin and details of the participants including demographic characteristics and the criteria for inclusion. We entered the study details into the Characteristics of included studies tables in Review Manager (RevMan) 5.4.1 (RevMan 2014). Any disagreements were resolved by consulting with a third review author.

The following details were also extracted if reported.

1. Trial methods: (a) allocation method; (b) sample size calculation; (c) masking of participants, trial staff and outcome assessors; (d) exclusion of participants after randomisation and the proportion and reasons for sample attrition at follow‐up.

2. Participants: (a) country of origin and study setting; (b) sample size; (c) age; (d) gender; (e) inclusion and exclusion criteria.

3. Intervention: (a) type; (b) materials and techniques used; (c) time of follow‐up.

4. Control: (a) type; (b) materials and techniques used; (c) time of follow‐up.

5. Outcomes: (a) primary and secondary outcomes mentioned in the Types of outcome measures section of this review.

Where stated, we recorded sources of funding. We used this information to aid assessment of investigator reporting bias and the validity of included trials.

Assessment of risk of bias in included studies

Two review authors (AE and GM) independently assessed the risk of bias for the selected trials using Cochrane's tool for assessing risk of bias (RoB 1), as described in section 8.5 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a; Sterne 2011).

We produced a 'Risk of Bias' table for each included study. For each domain, we provided a description of what was reported. We then used this information to judge whether the risk of bias was low, high or unclear. The two review authors compared their assessments; any inconsistencies between them were discussed and resolved.

We assessed the following domains as being at low, high or unclear risk of bias:

• random sequence generation (selection bias);

• allocation concealment (selection bias);

• blinding of participants and personnel (performance bias);

• blinding of outcome assessors (detection bias);

• incomplete outcome data addressed (attrition bias);

• selective outcome reporting (reporting bias);

• other bias.

We categorised and reported the overall risk of bias of each included study according to the following:

• low risk of bias (plausible bias unlikely to seriously alter the results) if all domains were considered to be at low risk of bias;

• unclear risk of bias (plausible bias that raises some doubt about the results) if one or more domains were assessed at unclear risk of bias; or

• high risk of bias (plausible bias that seriously weakens confidence in the results), if one or more domains were assessed at high risk of bias.

Measures of treatment effect

We calculated mean differences (MD) with 95% confidence intervals (CI) for continuous data, and risk ratios (RR) with 95% CI for dichotomous data. We contacted the corresponding authors of trials for original data where necessary.

Unit of analysis issues

We had anticipated that some included studies may have presented participant data from repeated or multiple site observations, or both, which may have led to unit of analysis errors. Had this been the case, we would have followed the advice provided in section 5.6 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020).

Dealing with missing data

In studies where data were unclear or missing, we contacted the principal investigators. If missing data were unavailable, we followed the advice given in section 10.12 of the Cochrane Handbook for SystematicReviews of Interventions (Higgins 2020).

Assessment of heterogeneity

We assessed clinical heterogeneity by examining the characteristics of the studies, the similarity between the types of participants, the interventions and the outcomes, as specified in the criteria for included studies. We had intended to assess statistical heterogeneity using a Chi² test and the I² statistic. We considered heterogeneity to be significant for the Chi² test when the P value was less than 0.10, with I² values of 30% to 60% indicating moderate heterogeneity, and over 60%, substantial heterogeneity (Higgins 2020).

Assessment of reporting biases

We had intended to assess publication bias according to the recommendations on testing for funnel plot asymmetry if a sufficient number of studies assessing similar interventions were identified for inclusion in this review, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020). If asymmetry had been identified, we had planned to assess other possible causes and explore these in the discussion.

Data synthesis

We pooled data from studies with similar participants, interventions and outcomes. We calculated a weighted treatment effect with the results expressed as mean difference for continuous data and odds ratio for dichotomous data. We carried out meta‐analyses where there were studies relating to similar comparisons reporting the same outcomes. We used the fixed‐effect model for meta‐analyses. We used additional tables to present the results from the included studies (Deeks 2011).

Subgroup analysis and investigation of heterogeneity

Where we found a sufficient number of studies included with moderate, substantial or considerable heterogeneity (see Assessment of heterogeneity), we had planned to carry out the following subgroup analyses.

• Type of non‐surgical method used

• Age category (adolescents versus adults)

• Type of orthodontic appliance

Sensitivity analysis

We undertook sensitivity analysis based on risk of bias (low risk of bias versus high or unclear risk of bias) to investigate the robustness of conclusions.

Summary of findings and assessment of the certainty of the evidence

We produced summary of findings tables (Table 1, Table 2) for the following outcomes, listed by priority.

1. Duration of orthodontic treatment, number of visits during active treatment (scheduled and unscheduled)

2. Rate of tooth movement

3. Improvement in occlusion

4. Patient‐centred outcomes: impact of fixed appliances on daily life, quality of life and pain experience

5. Harm arising during the course of orthodontic treatment: including gingival and other periodontal problems, anchorage loss and iatrogenic damage to teeth (e.g. caries or demineralisation and root resorption)

We assessed the certainty of the evidence according to GRADE as high, moderate, low or very low, with reference to the overall risk of bias for included studies, directness of evidence, consistency of results, precision of estimates and risk of publication bias.

Results

Description of studies

See Characteristics of excluded studies and Characteristics of included studies. 

Results of the search

The initial review was published in 2015 and had two included studies. Electronic searches to date (September 2022) identified a total of 6521 references. After removal of duplicates, 1902 records remained. We discarded 1771 of these and assessed the full text of 131 records. Of these 131, we rejected 55 and excluded 35 (33 studies) with reasons presented (see Characteristics of excluded studies). We included a total of 41 records in this review, reporting on 23 studies. Figure 1 shows the study selection process.

1.

Study flow diagram

Characteristics of design

This review included 23 parallel‐group RCTs reported in 41 articles (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Katchooi 2018; Kumar 2020; Lalnunpuii 2020; Lo Giudice 2020; Lombardo 2018; Miles 2012; Miles 2016; Nahas 2017; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015). NCT02868554 was not published in a peer reviewed journal by the time the current review was submitted for publication; however, review authors extracted data from the trial registration webpage. Ethical approval was obtained in all studies prior to commencement and recruitment of participants. Fourteen of the studies compared two groups (Abellán 2021; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Ghaffer 2022; Katchooi 2018; Lo Giudice 2020; Miles 2012; Miles 2016; Nahas 2017; Pavlin 2015; Reiss 2020; Taha 2020; Telatar 2020), eight compared three groups (Farhadian 2021; Hasan 2022; Kumar 2020; Lalnunpuii 2020; Lombardo 2018; NCT02868554; Siriphan 2019; Woodhouse 2015) and one compared four groups (Alam 2019).

Characteristics of settings and investigators

Of the 23 included studies in this review, four studies were conducted in the United States of America (NCT02868554; Pavlin 2015; Reiss 2020; Taha 2020), three in Italy (Caccianiga 2017; Lo Giudice 2020; Lombardo 2018), two each in Australia (Miles 2012; Miles 2016), India (Kumar 2020; Lalnunpuii 2020), Syria (AlSayed 2017; Hasan 2022), and Egypt (El Shehawy 2020; Ghaffer 2022), and one each in the United Kingdom (Woodhouse 2015), United Arab Emirates (Nahas 2017), Saudi Arabia (Alam 2019), Turkey (Telatar 2020), Iran (Farhadian 2021), Spain (Abellán 2021), Thailand (Siriphan 2019), and the USA and Canada (Katchooi 2018).

Nineteen studies were conducted in university hospital settings (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Kumar 2020; Lalnunpuii 2020; Lombardo 2018; Nahas 2017; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015), with orthodontists as well as postgraduate students treating participants under supervision; only four studies were conducted in an orthodontic practice setting (Katchooi 2018; Lo Giudice 2020; Miles 2012; Miles 2016).

Characteristics of participants

The trials involved a total of 1027 participants with various types of malocclusion. The recruited participants had a wide age range from 8 to 50 years. The age range in most studies spanned both childhood/adolescence and adulthood. One study recruited only children (Hasan 2022, 42 participants aged 8 to 10 years old); two studies recruited only adolescents (Miles 2012, 66 participants aged from 11 to 15 years; Miles 2016, 40 participants up to the age of 16 years), and three studies recruited only adults only (Katchooi 2018, 27 participants aged 18 years and older; NCT02868554, 33 participants aged 18 to 65 years old). Nahas 2017 did not specify chronological age, although 40 participants in the permanent dentition were included, while Alam 2019 did not report the age of the recruited participants. 

All but one study recruited participants of both sexes; Ghaffer 2022 included only adult female participants. 

Most studies involved treatment with fixed orthodontic appliances, while Katchooi 2018, NCT02868554 and Lombardo 2018 used removable orthodontic aligners. The participants in most studies presented with dental crowding in one or both arches. Some studies included participants who required dental extraction to relieve dental crowding and correct the malocclusion with space closure (AlSayed 2017; Kumar 2020; Lalnunpuii 2020; Lo Giudice 2020; Miles 2016; Pavlin 2015; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015), while other studies included participants who did not require dental extractions (Caccianiga 2017; El Shehawy 2020; Ghaffer 2022; Katchooi 2018; Lo Giudice 2020; Lombardo 2018; Miles 2012; Nahas 2017; Reiss 2020). Alam 2019 included participants being treated both with and without dental extractions. Two studies recruited participants for the treatment of anterior open bite (Abellán 2021; Hasan 2022). 

The percentage of participants lost to follow‐up ranged from 0% to 27%, with the maximum dropout being in Woodhouse 2015 for the secondary outcomes.

Characteristics of interventions

In this review, we classified the non‐surgical interventions for accelerating orthodontic tooth movement into two categories: light vibrational forces (LVF) and photobiomodulation therapy (low level laser therapy (LLLT) and light emitting diode (LED)). All trials provided a clear description of the treatment protocols except Alam 2019. Twelve studies (reported in 16 publications) assessed appliances delivering LVF (Katchooi 2018; Kumar 2020; Lombardo 2018; Miles 2012; Miles 2016; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015); 10 studies (reported in 12 publications) assessed low level laser therapy (LLLT) (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Lalnunpuii 2020; Lo Giudice 2020) and two studies assessed light‐emitting diode (LED) (Farhadian 2021; Nahas 2017) as an adjunct to increase the rate of orthodontic tooth movement (OTM). Some studies had more than one intervention group in addition to the control. Kumar 2020 and Lalnunpuii 2020 both had two intervention groups receiving non‐surgical adjunctive intervention with the stratification based on the ligation method of the fixed appliance, i.e. self‐ligation or conventional brackets. Farhadian 2021 had two intervention groups (LED and laser) in addition to the placebo control group. 

Light vibrational forces (LVF)

Three different types of vibrational appliances were used in the 12 studies that assessed the influence of light vibrational forces on the rate of orthodontic tooth movement. Most studies used the Acceledent device with vibrational frequency of 30 Hz and 0.25N (Katchooi 2018; Lombardo 2018; Miles 2016; NCT02868554; Pavlin 2015; Reiss 2020; Taha 2020; Telatar 2020; Woodhouse 2015); however, Miles 2012 used the Tooth Masseusse device with vibration frequency of 11 Hz and 0.06N, while Siriphan 2019 used modified electric tooth brushes with 0.60N and two different vibration frequencies (30 and 60 Hz). Kumar 2020 used a custom‐made oral vibration device with vibration frequency of 30 Hz. The devices had a mouthpiece for the patient to lightly bite into with a linked extraoral enclosure. In all the included studies, participants were instructed to use the vibrational appliance for 20 minutes daily.

Nine studies used vibrational appliances as an adjunct to fixed orthodontic appliances (Kumar 2020; Miles 2012; Miles 2016; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015), with three studies using the pre‐adjusted 0.018 x 0.025‐inch orthodontic bracket slot system (Miles 2012; Miles 2016; Pavlin 2015), while six used the pre‐adjusted 0.022 x 0.028‐inch orthodontic bracket slot system (Kumar 2020; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015). Three studies assessed the influence of vibrational forces on orthodontic treatment during the alignment stage (Miles 2012; Miles 2016; Woodhouse 2015), seven studies assessed the space closure stage (Kumar 2020; Miles 2016; Pavlin 2015; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015) and four studies assessed the full duration of treatment (Katchooi 2018; Lombardo 2018; Miles 2016; Woodhouse 2015).

Three studies used removable orthodontic aligners to assess the influence of adjunctive light vibrational forces on orthodontic treatment over the full treatment duration (Katchooi 2018; Lombardo 2018; NCT02868554).

Fixed orthodontic appliances

Alignment stage

Four studies assessed the influence of light vibrational forces on OTM during the alignment stage (Miles 2012; Miles 2016; Reiss 2020; Woodhouse 2015). All four studies included the mandibular arch only. Both Miles 2012 and Miles 2016 investigated the influence of light vibrational forces on the early alignment stage for a period of up to 10 weeks (5, 8 and 10 weeks) using the same initial (0.014‐inch nickel‐titanium) archwire in combination with a 0.018 x 0.025‐inch bracket slot system. Reiss 2020 investigated the influence of light vibrational forces on the alignment stage for up to three visits (4 to 6‐week intervals) using a standardised archwire sequence (0.014‐inch followed by 0.014 x 0.025‐inch copper nickel titanium) in combination with a 0.022 x 0.028‐inch bracket slot. Woodhouse 2015 investigated the full alignment in two stages using 0.022 x 0.028‐inch bracket slot system with a standardised archwire system. The initial alignment stage was described as the alignment achieved with the 0.014‐inch nickel titanium archwire and the final alignment stage was described as the end of alignment with the ligation of the working 0.019 x 0.025‐ inch stainless steel arch wire (Woodhouse 2015). The four included studies used Little's Irregularity index (LII) applied on study models to assess the improvement in the alignment of the mandibular teeth during the specified intervention period.

Space closure stage

Seven studies assessed the influence of light vibrational forces on the rate of OTM during the space closure stage (Miles 2016; Pavlin 2015; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015). Four studies assessed the rate of space closure in the maxillary arch only (Miles 2016; Pavlin 2015; Siriphan 2019; Taha 2020), one study assessed space closure in the mandibular arch only (Woodhouse 2015), while two studies assessed space closure in both arches (Kumar 2020; Telatar 2020).

All studies used conventional preadjusted fixed bracket systems except Kumar 2020 who used a self‐ligating bracket system (SmartClip). Most of the studies used a 0.022 x 0.028‐inch bracket slot system except Miles 2016 who used 0.018 x 0.025‐inch bracket slot dimension in combination with 0.016 x 0.022‐inch stainless steel archwire. The working archwire choice varied in the included studies which used 0.022 x 0.028‐inch bracket slot system depending on the space closure mechanics with most of the studies using 0.019 x 0.025‐inch stainless steel archwire for en masse space closure and for canine distalisation, some studies used 0.018‐stainless steel archwire (Taha 2020) while others used 0.016 x 0.022‐inch stainless steel archwire (Siriphan 2019). 

Three of the seven studies applied en masse space closure mechanics (Kumar 2020; Miles 2016; Woodhouse 2015), three studies involved canine distalisation (Siriphan 2019; Taha 2020; Telatar 2020), while Pavlin 2015 used anchorage reinforcement with orthodontic mini‐implants with the randomisation stratified according to space closure mechanics into either en masse retraction or canine distalisation. The orthodontic force applied for space closure varied in the included studies depending on the biomechanics used. Three studies applied en masse space closure with the use of 9 mm nickel titanium coil to deliver approximately 150 g of force bilaterally (Kumar 2020; Miles 2016; Woodhouse 2015). Siriphan 2019, Taha 2020 and Telatar 2020 applied 60 g, 180 g and 200 g, respectively, for canine retraction. Pavlin 2015 applied a retraction force of 180 g from the orthodontic miniscrew to the canine bracket; however, it was not specified if a different force magnitude was used with canine retraction compared to en masse retraction.

Four of the seven studies assessed the full space closure stage, while three studies assessed space closure for a specified duration (Kumar 2020; Miles 2016; Pavlin 2015; Woodhouse 2015). In particular, Siriphan 2019 and Taha 2020 evaluated a three‐month period and Telatar 2020 considered a time frame of six months of canine distalisation. All seven studies used a series of study models to calculate the rate of space closure. In addition, Siriphan 2019 also reported using lateral cephalometric radiographs to assess the angulation of the canines and molars. 

Full treatment duration

Woodhouse 2015, Miles 2016 and Kumar 2020 were the only three studies to investigate the influence of vibrational forces on OTM for the full duration of orthodontic treatment. All three studies used a standardised archwire sequence; however, with different bracket slot dimension systems. Woodhouse 2015 and Kumar 2020 used 0.022 x 0.028‐inch slots and Miles 2016 used 0.018 x 0.025‐inch.

Removable orthodontic aligners

Three studies assessed the effectiveness of light vibrational forces appliances on the rate of OTM using removable orthodontic aligners (Invisalign) for the full duration of treatment (Katchooi 2018; Lombardo 2018; NCT02868554). Lombardo 2018 had two intervention groups in addition to the control. The two intervention groups used vibrational forces similarly; however, one group changed aligners every 14 days while the other group changed aligners every 7 days. NCT02868554 had one intervention group where the vibrational appliance was used with aligners changed every 4 days and two control groups with different duration for aligners changing at 14 days and 4 days. Katchooi 2018 had only one intervention group in addition to the control group.

Photobiomodulation therapy

Low level laser therapy (LLLT)

Ten studies assessed the influence of LLLT on OTM (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Lalnunpuii 2020; Lo Giudice 2020). Eight out of ten studies used fixed devices with 0.022 x 0.028‐inch bracket dimensions with AlSayed 2017, El Shehawy 2020 and Ghaffer 2022 using conventional pre‐adjusted brackets, and Caccianiga 2017, Lalnunpuii 2020 and Lo Giudice 2020 using self‐ligating brackets. Alam 2019 used both self‐ligation and conventional preadjusted brackets within subgroups. Two studies did not use the multibracket orthodontic appliances; Hasan 2022 used posterior bite blocks for molars intrusion while Abellán 2021 used orthodontic mini‐implants and auxiliaries to intrude maxillary molars. 

All the studies assessed the influence of LLLT on OTM during the alignment stage except Lalnunpuii 2020 and Farhadian 2021 who assessed OTM during the space closure stage, and Abellán 2021 and Hasan 2022 who assessed OTM during the correction of anterior open bite with maxillary molar intrusion.

Low level laser devices 

AlSayed 2017 applied a LLLT dose in the intervention group using an 830‐nm wavelength laser device (CMS Dental ApS, 55 Wildersgade, 1408 Copenhagen K, Denmark) with a 2.25‐J/cm² irradiation dose. The laser beam was applied to each root of the six maxillary incisors. Each root was divided into two halves: cervical and apical. The LLLT device tip was applied to the centre of each half, perpendicular to the root and in direct contact with the mucosa from both the buccal and palatal sides so that there were four application points for each tooth with an exposure time of 1 minute/tooth. The LLLT application was repeated on days 3, 7, and 14 after the first application and every 15 days starting from the second month until the levelling and the alignment stage was completed.

Caccianiga 2017 applied LLLT in the intervention group using a diode laser emitting infrared radiation at 980 nm (Wiser; Doctor Smile–Lambda Spa, Brendola, VI). The plane wave optical fibre (AB 2799; Doctor Smile Lambda Spa) delivered a beam spot size of 1 cm² and irradiation was administered by positioning the optical fibre tip along the mandibular dental arch. Four dental segments (right first premolar‐canine, right lateral‐central incisors, left central‐lateral incisors, left canine‐first premolar) were consecutively irradiated for 8 seconds and two dental segments (right first molar‐second premolar, left second premolar‐first molar) for nine seconds, for a total of 50 seconds. The procedure was repeated three times at two‐minute intervals. All irradiation was performed with an output power of 1W using a continuous wave. The total energy density for the entire mandibular dental arch, corresponding to an exposure time of 150 seconds, was 150 J/cm², (1 J/cm² per second) including 27 J/cm² for each of the two first molar‐second premolar segments and 24 J/cm² for each of the remaining four dental segments.

Lalnunpuii 2020 used a 658 nm (Aluminium Gallium Arsenide) Semiconductor Diode laser (the Silberbauer CL mini 8‐658 EN 60601‐1‐2:2007‐07, Vienna, Austria, EU). The dose of irradiation was 2.29 J/cm² at 2.2 J and an output of 8mW. The duration of exposure was 10 seconds being delivered by direct contact on days 0, 3, 7 and 14 for the first month followed by every 15 days from the second month. Two irradiations were done both buccally and palatally/lingually from canine to canine. To ensure complete irradiation of the periodontium, the following protocol was followed: two doses were given in the cervical third (1 mesial/1 distal); two doses in the apical third (1 mesial/1 distal); and a single dose directed at the centre of the root. A similar process was repeated for the palatal/lingual side. The tip was held in contact with the tissue during application. This procedure was followed for all subsequent appointments. 

El Shehawy 2020 used gallium aluminium arsenide (Ga‐Al‐As) semiconductor diode laser (SMART™ PRO, LASOTRONIX, Poland) with a wavelength of 635 nm with the following set parameters; continuous mode, power output of 20 mW, fibre optic tip diameter of 2 mm, energy density of 6.5 J/cm2, exposure time of 10 s per point resulting in dose of 0.2 J per point, 2 J per tooth, and total energy of 12 J per session. The laser beam was applied to six mandibular anterior teeth where each root area was divided into 3 thirds; cervical, middle and apical. Laser was applied directly and perpendicular to target points on mesial and distal of cervical and apical thirds and on centre of middle third at 10 points, 5 facially and 5 lingually. The laser protocol was held on days 0, 3, 7, and 14 of first month and repeated for an additional two months. 

Lo Giudice 2020 used the ATP38 (Biotech Dental, Allee de Craponne, Salon de Provence, France). This device features a multi‐panel system emitting cold polychromatic lights with a combination of wavelengths from 450 to 835 nm depending on the field of action. This module provided six minutes of irradiation producing 48 J/cm² of fluency, calculated as the sum of the fluency produced by each light source (16 J/cm²) multiplied for the three active panels (16 J/cm² 3 = 48 J/cm²).  Three consecutive stages of irradiation in each session, for a total duration of 18 minutes and 144 J/cm² of fluency administered (i.e. 48 J/cm² x 3 stages). A rest time of 1 minute was set between each stage. Each LLLT session was performed every 14 days, including the date of bracket bonding, up to the end of the alignment stage. 

Alam 2019 used the Epic‐x Biolase device to apply LLLT. No details were published about the radiation dose, frequency or duration.

Abellán 2021 used a low‐power diode laser (Periowave; Ondine BioPharma) emitting at a wavelength of 670 nm, with a power of 150mW (measured with a Gentec XLP power detector in combination with a Gentec console. The radiation was applied through a flexible optical fibre connected to an autoclavable stainless steel handpiece designed by the user. This handpiece accommodates a light diffuser tip configured as a periodontal probe to allow access to the periodontal pocket. The diffuser tip moved smoothly around the gum on each of the dental surfaces (distal, mesial, vestibular, and palatal) of the molar to be intruded for three minutes for each surface (total 12 minutes) on days 0, 1, 2, 3, 4, and 7 of the beginning of the intrusion and in each monthly follow‐up.

In Farhadian 2021, LLLT was performed using a Cheese II dental diode laser device (Wuhan Gigaa Optronics Technology Corporation, Wuhan, China). The Ga Al As diode laser was used with a wavelength of 810 nm and a power of 100 mW. The diameter of the laser tip was 3.1 mm, and the energy density was 4 j/cm². LLLT was performed on days 0 (at the beginning of canine retraction), 3, 30 and, 60. The laser was irradiated to three points on the buccal and three points on the canine's palatal surface (cervical, mid‐root and apical), three seconds each point.

Hasan 2022 used a gallium aluminium arsenide (Ga‐Al‐As) laser with a continuous wavelength of 808 nm applied on the first day and on days 3, 7, and 14 of the first month, then every 15 days until the end of the treatment. The laser was applied in contact with the mucosa of the buccal (3 points) and palatal (3 points) sides of the permanent upper first molar and the first and second upper primary molars root tips on each side. The location of the LLLT on the primary upper molars was determined according to the location of the root tips of these molars on the panorama. The irradiation parameters of the LLLT were standard is through the whole treatment period and were set as follows: the power of 250 MW, the energy at 4 J, and the application time was 16 seconds per point. Participants were followed up in the same manner as what was performed in the FPBB (flat posterior bite blocks) group. 

Ghaffer 2022 used an Epic 10 diode laser machine (BIOLASE, Foothill Ranch, California, USA). This operates on continuous power mode with wavelength 940 +/‐ 10 nm, energy density 25.7 J cm² and power output 2.5 W, using an application tool (tooth‐whitening handpiece ((35 mm x 8 mm) = (2.8 cm²))), where the application site and duration is labially at the vestibule for 30 seconds. LLLT was applied on days 3, 7, and 14, then at one month, followed by every two weeks until alignment completion. 

Alignment stage

Two studies assessed the influence of LLLT on the alignment of the maxillary arch (Alam 2019; AlSayed 2017), while four investigated the mandibular arch alignment (Caccianiga 2017; El Shehawy 2020; Ghaffer 2022; Lo Giudice 2020).  AlSayed 2017 included participants that required dental extraction in the maxillary arch to relieve crowding. Caccianiga 2017, El Shehawy 2020, Ghaffer 2022 and Lo Giudice 2020 included cases that did not require extraction in the mandibular arch, while Alam 2019 included both extraction and non‐extraction cases.

Space closure stage

Only one study assessed the influence of laser therapy on OTM during the space closure stage (Lalnunpuii 2020). The authors used a self‐ligating (Smartclip) bracket system with 0.022 x 0.028‐inch bracket slot with a working 0.019 x 0.025 stainless steel wire. En masse space closure mechanics was used with bilateral force of 150 g for the entire space closure stage.

Molar intrusion for the correction of anterior open bite 

Two studies assessed the influence of LLLT on the correction of anterior open bite by the intrusion of maxillary molars (Abellán 2021; Hasan 2022). Abellán 2021 used orthodontic mini‐implants (1.6 mm in diameter and 10 mm in length). One in the buccal region mesial to the super‐erupted molar, and another in the palatal region distal to this molar. Auxiliary buttons were used to intrude the maxillary molars with the use of elastomeric power chain placed between the screw head and the button, a force of 75 g was applied. 

Hasan 2022 used acrylic posterior bite blocks for intrusion of maxillary molars.  The appliance consisted of transpalatal arch that connected the two acrylic blocks, extending across the palate between the primary second and the permanent first molars from the right side to the left side. This arch was 4 mm away from the palatal mucosa to avoid being embedded in the palatal mucosa during the posterior teeth intrusion. An acrylic posterior bite‐block covered the occlusal surfaces of the primary upper first and second molars and the permanent first upper molar. The thickness of the bite block was 2 mm greater than the freeway space. Also, the device had a tongue crib which was manufactured from a stainless‐steel round wire with a diameter of 0.9 mm. Cementation was performed using Glass Ionomer Cement (Vivaglass CEM PL, Ivoclar Vivadent). 

Light‐emitting diode LED

Two studies investigated the influence of LED compared to control on OTM using fixed orthodontic appliances (Farhadian 2021; Nahas 2017). 

In Nahas 2017, the intervention group received an OrthoPulse device from Biolux Ltd (Vancouver, Canada). Participants were instructed to use the device daily for 20 minutes producing light at a wavelength of 850 nm and a power output of 90 mW/cm². The estimated irradiation dose per session on the surface of the cheek was 108 J/cm². Tracking software was integrated into the LED device to evaluate the compliance rate based on recording of the number of sessions performed by each patient. A self‐ligating 0.022 x 0.028‐inch system was used with participants who required no dental extractions to relieve mandibular arch crowding. The entire alignment stage for the mandibular arch was assessed in this study. 

Farhadian 2021 used an intraoral LED device named Biolight, with a wavelength of 640 nm, energy density of 10 j/cm², and 40 mW/cm² power density. The inner part of the device has 2 pairs of diodes bilaterally located, irradiating the buccal surface of the canine and extraction site. At the beginning of canine retraction, participants were educated to use the device in the maxillary dental arch for five minutes a day.

Control conditions

In all studies, control group participants received either orthodontic fixed appliance or removable aligners without the use of adjunctive non‐surgical interventions. Katchooi 2018, Farhadian 2021 and Pavlin 2015 had the control group using a sham device, which was an inactive device that was held in the mouth and looked identical to the active devices, but did not deliver any non‐surgical intervention. Woodhouse 2015 was the only study to have a sham group in addition to the control group. 

Characteristics of outcomes

Outcomes assessed primarily included objective assessments of the rate of OTM as well as duration of treatment, in addition to secondary outcomes: orthodontically‐induced inflammatory root resorption, occlusal outcome evaluated using PAR scoring and subjective pain experience, as well as the reported use of analgesics during treatment. 

Specific clinical outcomes included the following.

Rate of orthodontic tooth movement (with fixed or removable orthodontic appliances)

The rate of OTM during the alignment stage was assessed by measuring the rate of the reduction in malalignment using Little's Irregularity Index (LII) during part or all of the orthodontic alignment stage (Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Ghaffer 2022; Lalnunpuii 2020; Miles 2012; Miles 2016; Nahas 2017; Reiss 2020; Woodhouse 2015). The rate of OTM was assessed during the space closure stage by measuring the rate of space closure for either canine retraction or en masse retraction (anterior segment) during part or all of the orthodontic space closure stage (Farhadian 2021; Kumar 2020; Lalnunpuii 2020; Miles 2016; Pavlin 2015; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015). The rate of OTM was assessed by measuring the amount of intrusion in the maxillary molars during the anterior open bite correction (Abellán 2021; Hasan 2022). 

Overall duration of orthodontic treatment

The overall orthodontic treatment duration was assessed in months from the start of orthodontic treatment marked by the ligation of the first archwire until the orthodontic appliance was debonded (Miles 2016; Woodhouse 2015). 

Duration of the full orthodontic alignment stage

The full duration of the orthodontic alignment stage treatment was assessed in months from the start of orthodontic treatment from the ligation of the first archwire ending with the ligation of the orthodontic working archwire, e.g. 0.019 x 0.025‐inch stainless steel archwire (AlSayed 2017; Caccianiga 2017; Ghaffer 2022; Lo Giudice 2020; Woodhouse 2015).

Orthodontic treatment outcome

The orthodontic treatment outcome was assessed by measuring the improvement in the occlusion or tooth position using specified indices by comparing the tooth position before and after a specified period of time in treatment or at the completion of treatment. The measures used include: evaluation of the change or outcome based on the use of a recognised occlusal index, the accuracy of OTM and successful completion of a set of orthodontic aligners. 

Treatment outcome index  

Woodhouse 2015 used the Peer Assessment Rating (PAR) index to assess improvement in the occlusal outcome at the end of treatment. Several studies (Katchooi 2018) used Little's irregularity index (LII) to assess the improvement in the alignment of the teeth after a course of orthodontic treatment.

Several studies assessed treatment outcomes using different methods and indices: Lombardo 2018 used validated software (VAM) to access accuracy of tooth movement; NCT02868554 assessed the percent reduction in Proximal Contact Point Discrepancy Index (PCPDI); Siriphan 2019 assessed the angulation and rotation of the canines and molars during space closure using study models and a lateral cephalometric radiograph. None of these outcome measurements were included in the current review as they did not meet the inclusion criteria.

Patient‐centred outcomes

Participants' perception of pain and discomfort 

Participants' perception of pain during orthodontic treatment was assessed in nine studies by asking participants to record pain and discomfort levels using a scoring system (visual analogue scale (VAS) or a numeric rating scale (NRS)) (Alam 2019; AlSayed 2017; Farhadian 2021; Ghaffer 2022; Miles 2012; Miles 2016; NCT02868554; Taha 2020; Woodhouse 2015). Eight studies assessed pain perception after the ligation of the first aligning archwire during the first week at different time points; Woodhouse 2015 also assessed pain after the ligation of the second aligning archwire. NCT02868554 used VAS to assess pain levels with clear aligners at several time points: 4 days, 2 weeks, 6 weeks and 12 weeks. Farhadian 2021 used McGill pain questionnaire to assess patient discomfort and pain. 

Participants' reported need of analgesics (painkillers) 

Three studies assessed the need for analgesia during orthodontic treatment to control pain associated with OTM (Miles 2016; NCT02868554; Woodhouse 2015). Miles 2016 assessed the reported need for analgesics at several time points during the first week after the ligation of the first (0.014‐inch NiTi) aligning archwire. Woodhouse 2015 assessed the overall reported consumption of analgesics during the first week after the ligation of the first (0.014‐inch NiTi) as well as the second (0.018‐inch NiTi) aligning archwires.

Oral health‐related quality of life 

Katchooi 2018 was the only study to assess the impact of applying light vibrational light forces compared to control group on reported oral health related quality of life. A customised questionnaire was used in this study, which was completed by the participants at three time points (at the start, middle and end of treatment).

Side effects of treatment

Orthodontically‐induced inflammatory root resorption (OIIRR) 

Woodhouse 2015 investigated OIIRR using 2‐dimensional radiographic assessment of the amount of maxillary central incisor root shortening by comparing the root length in millimetres before treatment and towards the end of the alignment stage. Pavlin 2015 also mentioned in the published article that OIIRR was assessed; however, no data were published. We tried to contact the authors for more information with no success. Abellán 2021 used 3‐dimensional radiographic CBCT technology to assess the volumetric OIIRR after intrusion of maxillary molars. 

Harm from treatment

Pavlin 2015, Katchooi 2018, Ghaffer 2022 and Lombardo 2018 reported on serious and non‐serious harm or safety‐related side effects throughout the treatment including headache and loosening of fixed appliance auxiliaries, e.g. temporary anchorage devices. 

Orthodontic inflammation markers

Reiss 2020 and Siriphan 2019 assessed the level of several oral inflammatory markers using a salivary sample or a sample from the gingival cervical fluid (GCF) at different time points. Siriphan 2019 assessed the levels of receptor activator of nuclear factor kappa‐B ligand (RANKL) and osteoprotegerin (OPG) during the first week of canine distalisation. Reiss 2020 assessed a wider range of inflammatory markers with 17 biomarkers analysed with the Multiplex analysis during the first three to four months of initial alignment.

Excluded studies

After removal of duplicates, 1902 unique records were identified. We discarded 1771 of these and assessed the full text of 131 records. Of these 131, we rejected 46 and excluded 44 with reasons presented (see Characteristics of excluded studies). We included a total of 41 records in this review, reporting on 23 studies. 

Risk of bias in included studies

None of the included studies had a low risk of bias in all domains. Further details of these assessments are given in the 'Risk of bias' table corresponding to each study in the Characteristics of included studies section. Overall ratings are also presented in the 'Risk of bias' summaries in Figure 2 and Figure 3.

2.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

3.

Risk of bias summary: each domain for all included studies 

Allocation

Selection bias can be minimised when participants and study personnel cannot foresee the upcoming assignment. This can be achieved by proper sequence generation and allocation concealment. 

Sequence generation 

In 20 out of the 23 included studies, the randomisation sequence generation procedure was described clearly and therefore these studies were assessed as low risk of bias for this domain (AlSayed 2017; Caccianiga 2017; Katchooi 2018; Lombardo 2018; Miles 2016; Nahas 2017; Pavlin 2015; Siriphan 2019; Woodhouse 2015 Abellán 2021; Ghaffer 2022; Hasan 2022; NCT02868554; Reiss 2020). In 15 of these studies, computer statistics software programmes were used to generate the randomisation sequence (Abellán 2021; Caccianiga 2017; El Shehawy 2020; Ghaffer 2022; Hasan 2022; Katchooi 2018; Kumar 2020; Lalnunpuii 2020; Lo Giudice 2020; Lombardo 2018; Miles 2016; NCT02868554; Pavlin 2015; Taha 2020; Woodhouse 2015), while four studies used selection of cards or envelopes for simple randomisation (AlSayed 2017; Nahas 2017; Siriphan 2019, Reiss 2020). Eight studies used block randomisation involving two (Katchooi 2018), four (Pavlin 2015), six (Miles 2012; NCT02868554) or 15 (Lombardo 2018) blocks. However, Farhadian 2021; Reiss 2020 and Lo Giudice 2020 did not mention how the block randomisation was performed. Stratification was applied in the randomisation procedure in five studies: Katchooi 2018 applied stratification according to gender and age;  Pavlin 2015 applied stratification according to age and mechanics of space closure; Reiss 2020 stratified according to gender; Farhadian 2021 stratified according to gender and bracket slot size, while Lo Giudice 2020 applied stratification according to both gender and the severity of crowding. 

Although Miles 2012 did not clearly describe the sequence generation method, the authors were contacted and confirmed that statistical software was used for sequence generation. Accordingly, it was rated as low risk of bias.

Farhadian 2021 was rated as unclear risk of bias as it was not clear how the sequence generation or the stratification were done. 

Both Alam 2019 and Telatar 2020 were rated as high risk of bias. Telatar 2020 used coin tossing for random sequence generation, which may result in an imbalanced sample size and baseline characteristics in the study groups especially because the sample size is considered relatively small (20 participants). Alam 2019 was rated as high risk of bias because the authors did not include enough details of the randomisation sequence generation with conflicting reports in two different peer‐reviewed journals. Although the study, Alam 2019, was published in the Bangladesh Journal of Medical Science as a "randomised clinical trial", the results were also published in the Pain Research and Management Journal in 2019 with the authors mentioning that the "study was designed and conducted according to the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)".

Allocation concealment

In nine studies (Farhadian 2021; Ghaffer 2022; Hasan 2022; Katchooi 2018; Lo Giudice 2020; Miles 2016; NCT02868554; Reiss 2020; Woodhouse 2015), the allocation concealment was described clearly and were therefore assessed as low risk of bias. In three studies, the allocation concealment was undertaken remotely (Katchooi 2018, NCT02868554; Woodhouse 2015). Six studies used sealed opaque envelopes to conceal the group allocation (Farhadian 2021; Ghaffer 2022; Hasan 2022; Lo Giudice 2020; Miles 2016; Reiss 2020).

We assessed 12 studies as having unclear risk of bias as the authors did not provide enough details to ensure safeguarding of the allocation process (AlSayed 2017; Caccianiga 2017; Kumar 2020; Lalnunpuii 2020; Lombardo 2018; Miles 2012; Nahas 2017; Pavlin 2015; Siriphan 2019 Abellán 2021; Taha 2020; Telatar 2020). 

Two studies were assessed as having high risk of bias (Alam 2019; El Shehawy 2020). Alam 2019 did not report information about allocation concealment. El Shehawy 2020 reported that the clinical assistants arbitrarily allocated patients into the study groups with no allocation concealment described. 

Performance bias

Performance bias can be reduced by blinding both participants and study personnel to the type of intervention allocated; however, performance bias can sometimes be unavoidable according to the nature of the intervention. Four studies were assessed as having low risk of bias with detailed reporting of the use of a sham (inactive) device that was held in the mouth and looked identical to the active devices without delivering any vibration (Farhadian 2021; Katchooi 2018; Pavlin 2015; Woodhouse 2015). Nineteen studies were assessed as having high risk of bias with no measures detailed about blinding participants nor clinicians (Alam 2019; AlSayed 2017; Caccianiga 2017; Katchooi 2018; Miles 2012; Miles 2016; Nahas 2017; Siriphan 2019, Abellán 2021; El Shehawy 2020; Ghaffer 2022; Hasan 2022; Kumar 2020; Lalnunpuii 2020; Lo Giudice 2020; NCT02868554; Reiss 2020; Taha 2020; Telatar 2020). 

Detection bias

Detection bias can be reduced by blinding the outcome assessors to the type of intervention allocated. Sixteen studies clearly described the details of the assessor blinding for the different studies outcomes and were assessed as low risk of bias (El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Katchooi 2018; Kumar 2020; Lalnunpuii 2020; Lo Giudice 2020; Lombardo 2018; Miles 2012; Miles 2016; Nahas 2017; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Woodhouse 2015). Seven studies did not report enough information regarding the blinding of the assessors and were assessed as high risk of bias (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; Hasan 2022; Taha 2020; Telatar 2020).

Incomplete outcome data

We assessed 14 studies as having low risk of attrition bias (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; Hasan 2022; Katchooi 2018; Kumar 2020; Lalnunpuii 2020; Lombardo 2018; Miles 2016; Pavlin 2015; Reiss 2020; Siriphan 2019; Woodhouse 2015). In 10 of these studies, all the randomised participants were included in the final analysis with no reported dropouts (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; Hasan 2022; Kumar 2020; Lalnunpuii 2020; Lombardo 2018; Miles 2016; Siriphan 2019), and in the other four studies, loss of follow‐up was reported (Katchooi 2018 1/27; Pavlin 2015 6/45, Reiss 2020 3/40; Woodhouse 2015 up to 21/81), and the authors demonstrated an appropriate rationale for the dropouts with the use of either intention‐to‐treat or sensitivity analysis.

For two studies, the risk of attrition bias was unclear (Miles 2012; NCT02868554). In Miles 2012, the authors reported incomplete outcome data with no clear description of how the missing data were dealt with. For the outcome rate of orthodontic tooth movement, two of 66 participants were lost to follow‐up; both the dropouts were from the experimental group. For the discomfort and pain outcome, eight of 66 did not complete the VAS at the five time points, five from the control group and three from the experimental group. It was unclear if the authors applied an intention‐to‐treat analysis. We also assessed NCT02868554 as having unclear risk of bias. The results presented on the trials register indicate three of 10 participants in the control group dropped out and one of 12 in the second intervention group. It does not seem intention‐to‐treat analysis was applied, but the results have not yet been published fully.

We assessed seven studies as having high risk of attrition bias (El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Lo Giudice 2020; Nahas 2017; Taha 2020; Telatar 2020). The authors reported no evidence of account for loss to follow‐up of participants and per‐protocol analysis was applied. 

Selective reporting

We assessed 10 studies as low risk of reporting bias as the studies were registered in a clinical trial registry, with all the planned outcomes reported clearly in the published peer‐reviewed articles (AlSayed 2017; El Shehawy 2020; Farhadian 2021; Hasan 2022; Katchooi 2018; Kumar 2020; Lalnunpuii 2020; Lombardo 2018; NCT02868554; Siriphan 2019). 

We assessed eight studies as having unclear risk of reporting bias as these studies had no protocol published nor were they registered in a clinical trial registry or platform (Abellán 2021; Caccianiga 2017; Ghaffer 2022; Lo Giudice 2020; Miles 2012; Miles 2016; Nahas 2017; Taha 2020). Woodhouse 2015 was also assessed as at unclear risk of bias as, according to the study registration, the trial authors had planned to assess OIIRR in relation to the mandibular incisors as a secondary outcome; however, the published data for the OIIRR was for the maxillary central incisors. The authors were contacted and confirmed that only the maxillary incisors were assessed with no additional radiographs taken for any other teeth (Appendix 7). 

We assessed three studies as having high risk of reporting bias (Alam 2019; Pavlin 2015; Reiss 2020). Alam 2019 published the outcomes in two‐peer reviewed journals with lack of consistency as the study was published as an RCT in the Bangladesh Journal of Medical Science in 2019 and then published as an observational study in another peer‐reviewed journal (Pain Research and Management Journal) in the same year. Reiss 2020 did not publish data about orthodontic pain, tooth mobility, and oral health and quality of life; however, these outcomes were listed in the study registry entry. In Pavlin 2015, we noticed that the authors used different measurement units to report the rate of canine retraction (mm per month) in the peer‐reviewed published article compared to the reported results in the clinical trial registry (mm per week).  

Other potential sources of bias

There was no reason for concern for other risk of bias in 15 studies (Caccianiga 2017; El Shehawy 2020; Kumar 2020; Lalnunpuii 2020; Lo Giudice 2020; Miles 2012; Miles 2016; Nahas 2017; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015; ; Ghaffer 2022; Hasan 2022; NCT02868554). Although not a source of bias per se, it should be noted we had concerns about inaccurate data reporting in Kumar 2020.

The risk of bias for other potential causes was assessed as unclear in five studies. In AlSayed 2017, it was noticed that the level of malalignment in the maxillary arch was higher in the control group compared to the intervention group (LLI 10.8 and 8.91, respectively). The authors did not report if this difference was statistically significant. Three studies had funding from the company manufacturing the vibrational devices (OrthoAccel Technologies) (Katchooi 2018; Lombardo 2018; Reiss 2020). Lombardo 2018 reported that the funding manufacturer was allowed to have access to the results; however, the final decision on publication was retained by the study authors. Katchooi 2018 did not publish details regarding the level of involvement of the funding manufacturer in the study. Reiss 2020 clearly mentioned that OrthoAccel Technologies had no contribution in relation to the conduct of the study. In addition, the study registry of Reiss 2020 suggested that two investigators would assess the models; however, in the published article it appeared that only one investigator assessed the models. In Abellán 2021, there was no mention of relatability of the results. 

The risk of bias for other potential causes was assessed as high in three studies (Alam 2019; Pavlin 2015). There were significant concerns about the design and presentation of the Alam 2019 study as the investigators included conventional ligation and self‐ligating systems, and moreover used an unusual archwire sequence. Pavlin 2015 was sponsored by OrthoAccel Technologies Inc, which is the manufacturer of the intervention appliance. The clinicaltrial.gov website mentions a time‐limited agreement between the principal investigators and the sponsor to review results before release to the public: "...the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo." Moreover, it was not clear if the primary outcome measure for the rate of orthodontic tooth movement was for the canines only or for en masse retraction of the six anterior teeth. Although stratification was done according to age and the technique of space closure (canine versus en masse retraction), the authors did not present the outcome for the technique of space closure subgroups. This may have influenced the rate of space closure in both groups. In the Farhadian 2021 study it was mentioned in the methods section mentioned that stratification was done based on gender and bracket prescription; however, how was this done was not explained, other than "according to clinicians preference", nor was it reported clearly in the results. 

Effects of interventions

See: Table 1; Table 2; Table 3

A total of 23 studies (involving 1027 participants) assessing the effectiveness of non‐surgical adjunctive interventions for accelerating orthodontic tooth movement were included in this review: 12 studies assessed the influence of vibrational light forces on orthodontic tooth movement (OTM) compared with control or placebo group (Katchooi 2018; Kumar 2020; Lombardo 2018; Miles 2012; Miles 2016; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015), 10 studies compared the influence of LLLT with control groups (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Lalnunpuii 2020; Lo Giudice 2020) and one study compared the influence of LED with control groups (Nahas 2017). Farhadian 2021 compared LED to LLLT as well as the control. 

We classified the non‐surgical interventions for accelerating orthodontic tooth movement as light vibrational forces (LVF) or photobiomodulation therapy (low level laser therapy (LLLT) and light‐emitting diode (LED)).

Light vibrational forces as an adjunct to orthodontic appliance treatment versus placebo or conventional orthodontic appliance treatment (control)

Twelve studies (involving 554 participants) assessed the effect of vibrational forces on the acceleration of orthodontic tooth movement (Katchooi 2018; Kumar 2020; Lombardo 2018; Miles 2012; Miles 2016; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015). All studies were assessed as having high risk of bias except two (Katchooi 2018; Woodhouse 2015), which were unclear. OTM was assessed during the alignment and space closure stages as well as the overall orthodontic treatment. The participants were treated with fixed orthodontic appliances except in two studies (Katchooi 2018; Lombardo 2018; NCT02868554), which used removable orthodontic aligners. 

Primary outcomes

Overall duration of active orthodontic treatment and total number of orthodontic appliance adjustment visits

Two included studies (Miles 2016 assessed as high risk of bias and  Woodhouse 2015 assessed as unclear risk of bias) involving 121 recruited participants investigated the influence of applying light vibrational forces during orthodontic treatment on the duration of the overall orthodontic treatment as well as the total number of orthodontic appliance adjustment visits. Both studies used Acceladent to deliver light vibrational forces. Although both studies included only participants whose orthodontic treatment plan required extractions to correct the malocclusion, they used different orthodontic bracket slot systems (0.022 x 0.028‐inch slot; Woodhouse 2015 and 0.018 x 0.025‐inch slot; Miles 2016).

Meta‐analysis was conducted that showed no evidence that duration of active orthodontic treatment was reduced, or increased, for application of light vibrational forces compared to the control: mean difference (MD) of 0.61 months (95% CI ‐2.44 to 1.22; P = 0.51; 2 studies, 73 participants; low‐certainty evidence; Analysis 1.1). In addition, there was no evidence that total number of orthodontic appliance adjustment visits was decreased or increased for application of light vibrational forces compared to the control: MD 0.32 visits (95% CI ‐1.69 to 1.05; P = 0.65; 2 studies, 73 participants; low‐certainty evidence; Analysis 1.2). We assessed the certainty of evidence for this comparison as low owing to the high risk of bias and imprecision (Table 1). 

1.1. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 1: Overall total orthodontic treatment duration: light vibrational forces vs control 

1.2. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 2: Total number of orthodontic appliance adjustment appointments: light vibrational forces vs control 

Rate of tooth movement during alignment stage

Four studies involving 221 participants assessed the influence of light vibrational forces on the rate of OTM during fixed orthodontic appliance tooth alignment in the mandibular arch. We assessed one at unclear risk of bias (Woodhouse 2015) and three as high risk (Miles 2012; Miles 2016; Reiss 2020). Three studies used Acceledent as the vibrational device and one (Miles 2012) used Tooth Masseusse. The rate of OTM was assessed during the alignment stage by quantifying the reduction in LII per arch at different time points: Miles 2012 and Miles 2016 assessed at 5, 8 and 10 weeks with the same aligning (0.014‐inch NiTi) archwire in combination with 0.018 x 0.025‐inch bracket slot system; Reiss 2020 considered the first three fixed appliance adjustment visits during the alignment stage with 4 to 6 week intervals using two consecutive archwires 0.014‐inch NiTi and 0.014 x 0.025‐inch NiTi archwires in combination with 0.022 x 0.028‐inch bracket slot system; and Woodhouse 2015 assessed the full alignment stage by dividing it into an early alignment stage, which the authors described as the visit where the 0.018‐inch NiTi was ligated, and the full alignment stage, which was described as the period that starts from the ligation of the first archwire and ends with the ligation of the working (0.019 x 0.025‐inch SS) archwire. All four studies assessed the rate of OTM by measuring the reduction in LII in the mandibular arch.

All four studies reported no evidence that the rate of OTM during the alignment stage was reduced, or increased, for application of light vibrational forces compared to the control at any of the time points assessed during the orthodontic alignment stage. Meta‐analysis was conducted showing the comparison between groups by assessing the reduction in the LII at two time stages of alignment: early alignment (4 to 6 weeks) with a mean difference of 0.12 mm (95% CI 1.77 to ‐2.01; P = 0.90; 3 studies, 144 participants; low certainty) and mid‐alignment (8 to 12 weeks) reflecting a difference of 0.18 mm (95% CI 0.83 to ‐1.20; P = 0.72; 4 studies, 175 participants; low certainty (Analysis 1.3; Analysis 1.4)). In addition, Reiss 2020 reported no evidence that OTM was reduced or increased for application of light vibrational forces compared to the control by measuring the rate of LII reduction at 12 to 16 weeks.

1.3. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 3: OTM early alignment (4‐6 weeks) in the form of the reduction in the LII index: light vibrational forces vs control 

1.4. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 4: OTM mid alignment (10‐16 weeks) in the form of the reduction in the LII index: light vibrational forces vs control 

Woodhouse 2015 was the only study amongst the included studies to publish data for the full alignment stage.  The authors reported no evidence that the rate of OTM, by assessing the reduction, in the LII was reduced, or increased, for application of light vibrational forces compared to the control (P = 0.60). 

The available low‐certainty evidence does not support the use of light vibrational forces to increase the rate of OTM during the alignment stage of fixed orthodontic treatment (Table 1).

Rate of tooth movement during space closure 

Seven studies involving 233 participants investigated the influence of light vibrational forces on the rate of OTM during the space closure stage with orthodontic extraction of either first or second premolars in the maxillary arch (Miles 2016; Pavlin 2015; Siriphan 2019 Kumar 2020; Taha 2020; Telatar 2020) and mandibular arch (Kumar 2020; Telatar 2020; Woodhouse 2015). One of these was rated as unclear risk (Woodhouse 2015) and six as high risk of bias (Kumar 2020; Miles 2012; Pavlin 2015; Siriphan 2019; Taha 2020; Telatar 2020). 

Five studies used Acceledent as the vibrational device; Siriphan 2019 used vibrational forces generated from an electric tooth brush; and Kumar 2020 used a custom‐made vibrational device. Four studies assessed the rate of OTM during space closure by measuring the space closed per month on study models for the whole space closure stage; Taha 2020 and Siriphan 2019 assessed space closure for three months and Telatar 2020 for six months. Siriphan 2019 used lateral cephalometric radiographs to assess the angulation of the teeth adjacent to the space during the space closure stage.  We assessed the certainty of evidence for this comparison as low to very low (Table 1). 

En masse space closure

Three studies assessed space closure through en masse retraction (Kumar 2020; Miles 2016; Woodhouse 2015). Meta‐analysis of two of the studies was conducted for en masse retraction space closure (Analysis 1.6), which suggested that there is no evidence of reduced or increased OTM in the intervention group when compared to the control group (MD 0.10 mm per month, 95% CI ‐0.08 to 0.29; P = 0.27; 2 studies, 81 participants; low certainty). 

1.6. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 6: Rate of OTM during space closure en‐masse (maxillary and mandibular arches): light vibrational forces vs control 

Additional analyses were conducted to assess studies that investigated the maxillary and mandibular arches separately, which again suggested no difference between interventions (Analysis 1.7; Analysis 1.8). 

1.7. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 7: Rate of OTM during space closure en‐masse (maxillary arch only): light vibrational forces vs control 

1.8. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 8: Rate of OTM during space closure en‐masse (mandibular arch only): light vibrational forces vs control 

Kumar 2020 reported a small but clinically insignificant difference between interventions for each outcome; however, we did not include data from Kumar 2020 due to concerns about inaccuracy in the reported data (see Characteristics of included studies). 

Canine distalisation

Three studies assessed space closure through canine distalisation (Siriphan 2019; Taha 2020; Telatar 2020). All three studies reported no evidence of a difference in the intervention group compared to the control. Meta‐analysis was conducted including two studies only showing there is no evidence that the rate of canine distalisation was reduced, or increased due to the use of light vibrational forces when compared to the control group (Taha 2020; Telatar 2020): MD 0.01 mm/month (95% CI 0.20 to ‐0.18; P = 0.92; 2 studies, 40 participants; very low certainty; Analysis 1.9). Siriphan 2019 assessed the influence of two different vibrational force frequencies (30 and 60 Hz) on the rate of space closure with two intervention groups as well as the control group for 3 months. The authors did not find a significant difference in the rate of space closure between the two groups (P < 0.05). The authors stated that the data was not normally distributed and they presented the data as median and IQR hence the reason this study data was not included in the meta‐analysis.

1.9. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 9: Rate of OTM during maxillary canine distalisation space closure: light vibrational forces vs control 

Pavlin 2015 stratified the study sample according to space closure mechanics (en masse and canine distalisation) reporting that the intervention group experienced more efficient space closure (MD 0.36 mm/month, 95% CI ‐0.01 to 0.73; P = 0.02). However, the published confidence intervals for the mean differences indicate imprecision in the reported results, which suggest interpreting the reported mean difference with caution. The data extracted from Pavlin 2015 was not included in the meta‐analyses as the subgroup data was not presented in the published article. 

Based on the low level of certainty, there is no evidence to support the suggestion that light vibrational forces can increase the rate of OTM during canine distalisation. There is a very low level of evidence to suggest that OTM during en masse space closure may be increased; however, any possible difference does not appear to be clinically significant. We assessed the certainty of evidence for this comparison as low to very low (Table 1). 

Change in angulation of the teeth adjacent to the space

Siriphan 2019 was the only study to assess the change in angulation of the teeth adjacent to the space closed using lateral cephalometric radiographs. The rate of molar movement and tipping, and canine rotation and tipping were not significantly different between groups (P > 0.05).

Aligners

Three studies (one with unclear and two with high risk of bias) involving 105 participants assessed the influence of light vibrational forces on OTM using removable orthodontic aligners (Katchooi 2018; Lombardo 2018; NCT02868554). All three studies used Invisalign aligners; however, with different aligner change interval regimens. Katchooi 2018 used 7‐day changes for both study groups, while Lombardo 2018 used 14‐day changes for two study groups (one with light vibrational force and one control) and 7‐day changes for the third study group (with light vibrational force). NCT02868554 had two non‐intervention groups with 14‐day routine wear and another with shortened 4‐day aligner wear, as well as one intervention study group with shortened 4‐day aligner wear and light vibrational force. 

The three studies used different criteria to measure changes in OTM with some reported outcomes that did not meet the current review inclusion criteria; hence, it was deemed inappropriate to combine the results of the three studies.

Katchooi 2018 used the reduction in the LII at the end of treatment compared to the start of the treatment. No evidence of a difference was found between the light vibrational and the control groups in the mean reduction of the LII in the maxillary arch (MD 0.2, 95% CI ‐1.51 to 1.10; P = 0.74) and the mandibular arch (MD ‐0.18, 95% CI ‐17.7 to 2.12; P = 0.85). NCT02868554 assessed several outcomes to compare between the non‐intervention group and the intervention with both having shortened aligner wear 4‐day changes. The rate of OTM during the first 12 weeks was increased in the intervention group compared to the non‐intervention group: 0.0243 (SD +/‐ 0.0163) and 0.0202 (SD +/‐0.0135), respectively. However, this reported difference was not statistically significant. The percentage reduction in the proximal contact point discrepancy was increased in the intervention group compared to the non‐intervention group: 29.12 (SD +/‐ 10.77) and 23.71 (SD+/‐ 11.02), respectively. However, this reported difference was not statistically significant. 

Secondary outcomes

Patient‐centred outcome: patient perception of pain and discomfort

Five studies (four rated as high risk of bias and one as unclear risk of bias) involving 208 participants assessed patient perception of pain and discomfort using a 100 mm VAS while assessing the effectiveness of light vibrational forces on rate of OTM (Miles 2012; Miles 2016; NCT02868554; Taha 2020; Woodhouse 2015). Three studies assessed pain perception during the alignment stage. In the first week (at different time points) after the ligation of a 0.014‐inch NiTi in the maxillary or mandibular arches with either 0.018 x 0.025‐inch bracket slot system (Miles 2012; Miles 2016) or 0.022 x 0.028‐inch bracket slot system (Woodhouse 2015.) In addition, Woodhouse 2015 assessed pain perception after the ligation of the second aligning archwire (0.018‐inch NiTi). Taha 2020 assessed patient perception of pain and discomfort during the canine distalisation stage at different time points within the first week. NCT02868554 assessed patient's perception of pain and discomfort during aligner treatment. 

Pain and discomfort during treatment: the first aligning archwire

Pain and discomfort increased 4 to 6 hours after archwire ligation and declined gradually after 3 to 7 days with minimal difference between the intervention and control groups. None of the three studies reported differences between the control and experimental groups in perception of pain during the first week of the initial aligning archwire. Meta‐analysis demonstrated no evidence that patient's perception of pain and discomfort was reduced, or increased, due to the use of the light vibrational forces when compared with control at any of the time points assessed.

There was no evidence that light vibrational forces reduced, or increased, pain and discomfort at any of the time points assessed with the first aligning archwire. Immediately after ligating the first aligning archwire, the mean difference on the 100 mm VAS was ‐2.56 mm (95% CI ‐2.35 to 7.47; P = 0.31; 3 studies; 153 participants; low‐certainty evidence; I² = 0%; Analysis 1.10). Similar findings were observed at 4 to 6 hours (MD 0.99 mm, 95% CI ‐8.83 to 6.85; P = 0.80; 3 studies; 153 participants; low‐certainty evidence; I² = 0%; Analysis 1.11), one day (MD 2.93 mm, 95% CI ‐11.25 to 5.39; P = 0.49; 3 trials, 153 participants; I² = 0%; Analysis 1.12), three days (MD 0.48 mm; 95% CI ‐7.13 to 6.18; P = 0.89; 3 trials, 153 participants; I² = 0%; Analysis 1.13) and seven days (MD ‐0.04 mm, 95% CI ‐2.97 to 3.05; P = 0.98; 3 trials, 153 participants; I² = 9%; Analysis 1.14).

1.10. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 10: Patient perception of pain immediately after initial wire ligation: light vibrational forces vs control 

1.11. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 11: Patient perception of pain after 4‐8 hours from the initial archwire ligation: light vibrational forces vs control 

1.12. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 12: Patient perception of pain after 1 day from the initial archwire ligation: light vibrational forces vs control 

1.13. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 13: Patient perception of pain after 3 days from the initial archwire ligation: light vibrational forces vs control 

1.14. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 14: Patient perception of pain after 7 days from the initial archwire ligation: light vibrational forces vs control 

Pain and discomfort during treatment: the second aligning archwire

Woodhouse 2015 was the only study to extend the assessment of pain and discomfort to the first week after ligation of the second aligning archwire (0.018 NiTi). The authors reported no benefit from the vibrational forces in reducing pain and discomfort. There was no evidence of a difference between the intervention, control and placebo groups at assessed time points except after the first day when more pain and discomfort were reported in the intervention group (mean 53.18, SD 31.18) compared to both the control (mean 34.52, SD 25.39) and placebo group (mean 34.96, SD 28.13). This difference was found to be statistically significant (P = 0.028) (Analysis 1.18).

1.18. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 18: Patient perception of pain after 1 day from the second aligning archwire ligation: light vibrational forces vs control 

Pain and discomfort during treatment: space closure 

Taha 2020 assessed patient perception of pain and discomfort during maxillary canine distalisation. The authors reported that there is no evidence that light vibrational forces can reduce, or increase, pain and discomfort when compared to a control group. No statistical analysis was published. 

Pain and discomfort during treatment: aligners 

NCT02868554 assessed patient perception of pain and discomfort during aligner treatment for 12 weeks. The pain score was higher in the intervention group compared to non‐intervention group; 1.58 SD+/‐ 1.38 and 0.68 SD +/‐ 1.23, respectively.  The authors reported that there is no evidence that light vibrational forces can significantly reduce, or increase, pain and discomfort when compared to a control group. 

Patient‐centred outcome: reported consumption of analgesics (painkillers)

Three studies (two at high risk of bias and the other at unclear risk) assessed the influence of light vibrational forces on patient‐reported analgesic consumption following engagement of initial archwires during the alignment stage (Miles 2016; Woodhouse 2015). NCT02868554 assessed patient‐reported analgesic consumption during the aligners' treatment. 

The first aligning archwire

Both Miles 2016 and Woodhouse 2015 assessed the overall reported analgesic consumption during the first week after the ligation of the initial archwire. There was no evidence that patient consumption of analgesics was reduced, or increased, due to the use of light vibrational forces when compared to control (RR 1.64, 95% CI 0.60 to 4.53; P = 0.34; 2 studies, 95 participants; low‐certainty evidence; Analysis 1.15). 

1.15. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 15: Patients' reported need for analgesics during the first week of the initial aligning archwire: light vibrational forces vs control 

In addition, Miles 2016 assessed analgesic consumption at specific time points (immediately after ligation and at 6 to 8 hours, 1 day, 3 days and 7 days). The authors reported no reduction in patient‐reported consumption of analgesics between intervention and control groups at any time points assessed except 24 hours (RR 0.63, 95% CI 0.44 to 0.92; P < 0.01). 

The second aligning archwire

Woodhouse 2015 was the only study to assess reported analgesic consumption following the ligation of the second aligning archwire. Although, the prevalence of analgesic consumption for the whole study sample was significantly reduced after the second visit compared with the first visits (34% and 69%, respectively), there was no evidence of a difference (P = 0.90) between study groups after the second visit, with a similar proportion (35%) of participants in both groups reporting consumption of analgesics (9/28 in the intervention group and 8/25 in the control group).

We assessed the certainty of evidence for patient‐centred outcomes as low (Table 1).

During aligner treatment 

NCT02868554 assessed the need for analgesics during 12 weeks of aligner wear. The authors reported that there is no evidence that light vibrational forces can significantly reduce, or increase, pain and discomfort when compared to a control group. 

Quality of life

Katchooi 2018 (unclear risk of bias) was the only study to assess the impact of applying light vibrational forces on patient‐reported oral health related quality of life (OHRQoL). The use of light vibrational forces had no statistically significant (P > 0.05) effect on OHRQoL when used in conjunction with orthodontic aligners.

Orthodontic treatment occlusal outcome

Woodhouse 2015 (unclear risk of bias) involving 81 participants with 22 dropouts, was the only study to report on the orthodontic treatment occlusal outcome at the end of treatment. This was assessed by comparing reduction in the Peer Assessment Rating (PAR) index. Both the absolute and percentage improvement in the PAR index were reported for the intervention group (median 28.0, IQR 21.0, 38.0 and median 88.9, IQR 80.9, 94.4, respectively), control group (median 29.0, IQR 24.0, 31.0 and median 91.2, IQR 85.0, 93.5, respectively) and placebo group (median 27.0, IQR 20.0, 35.0 and median 90.0, IQR 87.5, 92.0, respectively). There is no evidence that occlusal outcomes was reduced, or increased due to the use of light vibrational forces when compared to the control or the placebo groups (P = 0.91 and P =0.71, respectively). 

Orthodontically‐induced inflammatory root resorption (OIIRR)

Woodhouse 2015  was the only included study (involving 81 participants with 9 dropouts) to assess the influence of light vibrational forces on the severity of OIIRR when compared to control and placebo groups. The authors investigated OIIRR by comparing the root length reduction in the upper central incisors using long‐cone periapical radiographs taken before the start of orthodontic treatment and at the end of the alignment stage. OIIRR of the upper central incisors was measured for the intervention (mean 1.09 mm, SD 0.64), control (mean 1.00 mm, SD 0.90) and placebo (mean 1.16 mm, SD 0.94). There is no evidence to suggest that OIIRR was reduced, or increased, due to the use of light vibrational forces when compared to the control groups (MD 0.09 mm, 95% CI ‐0.35 to 0.53; P = 0.69; 1 study, 50 participants). We assessed the certainty of evidence as low (Table 1). 

Harms arising during the course of orthodontic treatment

Five studies assessed other harms arising during the intervention (Katchooi 2018; Lombardo 2018; Pavlin 2015; Reiss 2020; Taha 2020). No serious adverse effects were reported. Pavlin 2015 reported a similar number of minimal non‐serious adverse effects in the intervention (5/23; 21.7%) and control (5/22; 22.7%) groups, with a RR of 0.96 (95% CI 0.32 to 2.85). The non‐serious adverse effects included headache, discomfort and loosening of temporary anchorage devices.

Other outcomes

Cost of treatment was not investigated in any of the included studies.

Low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment versus conventional orthodontic appliance treatment (control)

Ten studies, involving 423 participants, assessed the influence of LLLT as an adjunctive intervention to accelerate OTM compared to control group with conventional orthodontic appliances (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Lalnunpuii 2020; Lo Giudice 2020). All 10 studies used fixed orthodontic appliance. Six studies assessed the influence of LLLT on OTM during the alignment stage, Lalnunpuii 2020 and Farhadian 2021 assessed the space closure stage, while Abellán 2021 and Hasan 2022 assessed the correction of anterior open bite by intrusion of maxillary molars. We rated all studies as high risk of bias.

Primary outcome

Duration of total overall orthodontic treatment and total number of orthodontic appliance adjustment visits

No study included in this systematic review was found to report on the influence of LLLT on the total overall orthodontic treatment duration nor the total number of orthodontic appliance adjustment visits to complete a course of orthodontic treatment.

Duration of orthodontic alignment stage

Four studies (all assessed as high risk of bias) assessed the influence of LLLT on the duration of the fixed orthodontic appliance alignment stage with a total sample of 172 participants (AlSayed 2017; Caccianiga 2017; Ghaffer 2022; Lo Giudice 2020). All four studies reported shorter orthodontic alignment duration in the LLLT groups compared to the control groups. Caccianiga 2017 reported a mean difference of 72.30 days (95% CI ‐83.80 to ‐60.80); AlSayed 2017, a mean difference of 28 days (95% CI ‐39.34 to ‐16.66), Lo Giudice 2020, a 57‐day reduction in the median duration with LLLT compared to the control group (P < 0.001), and Ghaffer 2022, a mean difference of 41.3 days (95% CI ‐70.30 to ‐12.30).

Meta‐analysis was conducted showing that there is some evidence to suggest that the duration of the orthodontic alignment stage can be reduced by use of LLLT when compared to control group: MD ‐48.87 days, 95% CI ‐56.48 to ‐41.26; P < 0.001; 3 studies, 92 participants; I² = 97%; very low level of certainty; Analysis 2.1; Table 2). The study by Lo Giudice 2020 was not included in the meta‐analysis as the outcomes were reported as medians; however, the authors also reported a statistically and clinically significant difference favouring the LLLT group.  

2.1. Analysis.

Comparison 2: Effect of low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 1: Orthodontic alignment duration: LLLT vs control

Number of visits during the alignment stage

Only two studies (assessed as high risk of bias) with 136 participants were included assessing the influence of LLLT on the number of visits required during the alignment stage in the mandibular arch involving non‐extraction cases (Caccianiga 2017; Lo Giudice 2020). 

Meta‐analysis was conducted showing that there is some evidence to suggest that the use of LLLT can reduce the number of visits required for fixed orthodontic appliance adjustment when compared to control: median difference of ‐2.25 visits (95% CI ‐2.52 to ‐1.97; P < 0.00001; 2 studies, 136 participants; I² = 69%; very low level of certainty; Analysis 2.2; Table 2). It is important to interpret the outcome from this analysis with caution as the heterogeneity was found to be high though not statistically significant (I² = 69%; P = 0.07).

2.2. Analysis.

Comparison 2: Effect of low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 2: Number of orthodontic appliance adjustment appointments during the alignment stage: LLLT vs control 

Rate of orthodontic tooth movement 

Alignment stage 

Four studies (all rated as of high risk of bias) with 114 participants assessed the influence of LLLT on the rate of OTM during the alignment stage (AlSayed 2017; Alam 2019; El Shehawy 2020; Ghaffer 2022). AlSayed 2017 assessed maxillary arch alignment for participants with premolar extractions by quantifying the percentage improvement in the LII at several time points from the start of treatment, 1 month, 2 months and at the end of alignment. El Shehawy 2020 and Ghaffer 2022 assessed the mandibular arch alignment on non‐extraction cases for several months. 

Meta‐analysis was conducted including only two studies (El Shehawy 2020; Ghaffer 2022) based on percentage reduction of the LII in the mandibular arch at the end of the first (Analysis 2.3) and second month (Analysis 2.4) of initial alignment. There is no evidence to suggest that rate of OTM was reduced, or increased, with the application of LLLT compared to the control by the end of the first month: MD 1.63 %, 95% CI ‐2.60 to 5.86; P = 0.45; 2 studies, 56 participants; very low level of certainty) nor the end of the second month: MD 3.75%, 95% CI ‐1.74 to 9.24; P = 0.18; 2 studies, 56 participants; very low level of certainty; Table 2). It is important to interpret the outcome from this analysis with caution as the heterogeneity was found to be high. 

2.3. Analysis.

Comparison 2: Effect of low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 3: OTM early alignment  (4 weeks)  percentage reduction in the LII: LLLT vs control

2.4. Analysis.

Comparison 2: Effect of low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 4: OTM early alignment  (8 weeks) percentage reduction in the LII: LLLT vs control

AlSayed 2017 reported increase in the maxillary LII percentage improvement in the LLLT group compared to the control group. The differences in the first and second months were found to be statistically significant (P = 0.004 and P = 0.001, respectively). However, at the end of the alignment stage there was no evidence of a difference between the LLLT group (mean 94.24% SD +/‐ 3.65) and control group (mean 94.20% SD+/‐ 2.81; P = 0.973). Due to the poor quality design and high risk of bias, the results from Alam 2019 were not included in quantitative or qualitative analysis.

Space closure stage 

Only two studies (assessed as high risk of bias) involving 105 participants assessed the influence of LLLT on the rate of OTM during the space closure stage (Farhadian 2021; Lalnunpuii 2020). The first premolars were extracted with the rate of OTM assessed in both the maxillary and mandibular arches in Lalnunpuii 2020 using en masse retraction mechanics, while Farhadian 2021 assessed canine retraction in the maxillary arch only. Due to the different biomechanics in space closure used in the two studies, it was deemed impossible to combine data for meta‐analysis.  

Lalnunpuii 2020 reported increased rate of space closure with the LLLT with conventional brackets group when compared to the control in the maxillary arch. There is a little evidence to suggest that rate of OTM during space closure can be increased on the application of LLLT compared to control (right side MD 0.18 mm/month, 95% CI 0.10 to 0.26, P < 0.001; left side MD: 0.18 MM/month, 95% CI 0.08 to 0.28, P < 0.001; 1 study, 65 participants; very low level of certainty) as well as the mandibular arch (right side MD 0.16 mm/month, 95%CI 0.13 to 0.19, P < 0.001; left side MD 0.18 mm/month, 95% CI 0.16 to 0.20, P < 0.001; 1 study; 65 participants; very low level of certainty; Table 2). 

Farhadian 2021 reported an increased rate of maxillary canine retraction with the LLLT with conventional bracket group when compared to the control in the maxillary arch. Although the authors reported P = 0.01, the 95% confidence intervals included zero (MD 0.01 mm/day, 95% CI 0 to 0.02; P = 0.01; 1 study, 37 participants; very low level of certainty). There was insufficient evidence to suggest that LLLT can increase or decrease the rate of OTM during canine distalisation/space closure stage.

Maxillary molar intrusion for the correction of anterior open

Two studies (both rated as high risk of bias) involving 62 participants assessed maxillary molars intrusion for the correction of anterior open bite. The two studies applied different mechanics for maxillary molar's intrusion; Abellán 2021 used orthodontic mini‐implants, bondable buttons and elastomeric chain, while Hasan 2022 used acrylic flat posterior bite blocks (FPBB). It was deemed inappropriate to pool the data from the two studies into meta‐analysis due to the difference in appliances and biomechanics applied. 

Abellán 2021 assessed the amount of maxillary molar intrusion using 3D intra oral scanner at two point intervals, 3 and 6 months. The authors reported there is no evidence to suggest that the amount of molar intrusion was significantly increased or reduced with the application of LLLT compared to the control at 3 months (mean 1.25 mm, SD +/‐ 0.72, and 1.72 mm, SD +/‐ 0.75, respectively) and 6 months (mean 1.09 mm, SD +/‐ 0.54, and 1.28 mm, SD +/‐ 0.46, respectively). In addition, there is no evidence to suggest that the rate of maxillary molar intrusion per months was significantly increased or reduced with the application of LLLT compared to the control at 3 months (mean 0.42 mm/month, SD +/‐ 0.24, and 0.58 mm, SD +/‐ 0.25, respectively), and 6 months (mean 0.43 mm/month, SD +/‐ 0.23, and 0.44 mm/month, SD +/‐ 0.13, respectively). 

Hasan 2022 assessed radiographically the amount of maxillary molar's intrusion using acrylic FPBB. The authors reported an increased molar intrusion in the FPBB + LLLT compared to FPBB (mean 1.251 mm, SD +/‐ 0.32 and 0.82 mm SD +/‐ 0.37, respectively; P = 0.018). In addition, the duration required for the correction of anterior open bite was reduced in the FPBB + LLLT compared to FPBB (mean 7.07 months, SD +/‐ 1.54, and 9.42 months, SD +/‐ 2.31, respectively; P = 0.001). 

Secondary outcomes

Orthodontically‐induced inflammatory root resorption (OIIRR)

Abellán 2021 assessed OIIRR using CBCT after the intrusion of the maxillary molars. There is no evidence to suggest that OIIRR volume during molar intrusion was significantly increased or reduced with the application of LLLT compared to the control group. The authors did not publish the statistical test results. 

Periodontal health 

Abellán 2021 assessed periodontal health after the intrusion of maxillary molars using clinical parameters such as plaque index, pocket depth, and bleeding of probing. There is no evidence to suggest that the periodontal health was significantly increased or reduced with the application of LLLT compared to the control group. The authors did not publish the statistical test results. 

Patient‐centred outcome: perception of pain and discomfort

Only three studies (rated as at high risk of bias) evaluated the influence of LLLT on the perception of pain and discomfort in the maxillary arch alignment (Alam 2019), mandibular arch alignment (Ghaffer 2022) and space closure (Farhadian 2021) stages. 

Ghaffer 2022 assessed pain perception using VAS for the first 7 days during the alignment stage. They reported no increase or decrease in the pain and discomfort when using LLLT compared to control in all 7 days except the 5th day (MD 1.6; 95% CI 3.1 to 0.1; P = 0.035). 

Farhadian 2021 used a modified McGill pain questionnaire, along with a VAS to assess the pain during the first visit with no specific time point. Based on the VAS, the authors reported no significant difference between the LLLT group mean (3.1, SD+/‐ 2.4) and the control group mean (3.5, SD+/‐2.1). It was deemed impossible to pool the data from the two studies in meta‐analysis due to the high clinical heterogeneity with each study assessing pain in a different treatment stage. 

Alam 2019 used a VAS to assess the pain during the first week (at 4 hours, 24 hours, 3 days and 7 days) of the alignment of ectopic canines. The authors reported that patient perception of pain and discomfort was significantly less in the LLLT group compared to the control group in the self‐ligating bracket subgroup for three out of four time points assessed. Due to the poor quality design and high risk of bias, the results from Alam 2019 were not included in quantitative or qualitative an analysis.

Harms arising during the course of orthodontic treatment

Ghaffer 2022 was the only study to assess harms arising during the LLLT intervention. No serious harms were reported other than gingivitis associated with plaque accumulation.

Light‐emitting diode (LED) as an adjunct to orthodontic appliance treatment versus conventional orthodontic appliance treatment (control)

Two studies (both assessed as high risk of bias) involving 80 participants evaluated the influence of the use of LED as an adjunct to accelerate OTM with conventional orthodontic appliances (Farhadian 2021; Nahas 2017).

Duration of orthodontic alignment stage 

 Nahas 2017 assessed the influence of LED during the full treatment duration. Although 40 participants were recruited, only 85% were analysed, with six participants excluded with no accounting for the dropouts. The study suggests that the duration of orthodontic treatment for mandibular arch alignment was reduced by the application of LED compared to the control (MD 24.5 days, 95% CI 6.55 to 42.45; P = 0.043; 1 study, 34 participants; very low certainty). See Table 3. 

Rate of orthodontic tooth movement 

Space closure stage 

Farhadian 2021 assessed the influence of LED on OTM during the canine retraction phase using fixed appliances. The authors reported slight increase in the rate of maxillary canine retraction with the LLLT with the conventional brackets group when compared to the control in the maxillary arch (mean 0.029 mm/day, 95% CI 0.02 to 0.03 and mean 0.023 mm/day, 95% CI 0.02 to 0.03, respectively). There is no evidence to suggest that OTM during canine retraction was reduced, or increased, due to the use of LED when compared to the control groups (P = 0.17; 1 study, 39 participants; very low level of certainty).

Patient‐centred outcome: perception of pain and discomfort

Farhadian 2021 used a modified McGill pain questionnaire, along with a VAS to assess pain during the first visit with no specific time point. Based on the VAS, the trial authors reported no significant difference between the LED group mean 4.3 (SD+/‐ 2.4) and the control group mean 3.5 (SD+/‐2.1). 

Harms arising during the course of orthodontic treatment

None of the included studies assessed harms arising during the LED intervention.

Discussion

Summary of main results

See Table 1, Table 2 and Table 3 for a summary of the main results.

A total of 23 RCTs met the inclusion criteria for this review. The studies involved 1027 participants. We judged 21 of the studies to be at high risk of bias overall; the other two we judged to be unclear (Katchooi 2018; Woodhouse 2015). The studies investigated the influence of three different types of non‐surgical adjunctive interventions on orthodontic tooth movement (OTM). Twelve studies assessed the influence of light vibrational forces (Katchooi 2018; Kumar 2020; Lombardo 2018; Miles 2012; Miles 2016; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015), nine assessed the influence of low level laser therapy (LLLT) (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Hasan 2022; Lalnunpuii 2020; Lo Giudice 2020) and two assessed the influence of light‐emitting diode (LED) (Farhadian 2021; Nahas 2017). To assess the influence of light vibrational forces, we conducted meta‐analyses for the duration of orthodontic treatment, number of appointments required to adjust the fixed orthodontic appliance, rate of orthodontic tooth movement during the alignment and space closure, patient perception of pain at different time points and patient‐reported need for analgesics at different time points during the first week of treatment. To assess the influence of LLLT, we conducted meta‐analyses for the alignment stage and number of appointments, and rate of orthodontic tooth movement during the alignment stage. Only two studies investigated the influence of LED and no meta‐analysis was conducted. The certainty of evidence for each outcome was also assessed.

Light vibrational forces versus placebo or control during orthodontic treatment

This comparison included 12 RCTs, with a total of 554 participants, (Katchooi 2018; Kumar 2020; Lombardo 2018; Miles 2012; Miles 2016; NCT02868554; Pavlin 2015; Reiss 2020; Siriphan 2019; Taha 2020; Telatar 2020; Woodhouse 2015), which assessed the effectiveness of light vibrational forces on OTM (9 studies used fixed orthodontic appliances and 3 studies used aligners for orthodontic treatment). All but two studies were rated as high risk of bias; these were judged to be unclear (Katchooi 2018; Woodhouse 2015). Three different types of light vibrational devices were used in the 11 included RCTs. Most studies used the Acceledent device with vibrational frequency 30 Hz and force of 0.25N (Katchooi 2018; Lombardo 2018; Miles 2016; NCT02868554; Pavlin 2015; Taha 2020; Telatar 2020; Woodhouse 2015). Miles 2012 used the Tooth Mousse device with vibration frequency of 11 Hz and force of 0.06N; while Siriphan 2019 and Kumar 2020 used customised devices with vibrational frequencies 30 to 60 Hz and force of 0.6 N. In all studies, they instructed participants to use the vibrational appliance for 20 minutes daily.

The results from this review indicate that there is low‐certainty evidence to suggest that the application of light vibrational forces during orthodontic treatment (fixed or removable appliances) has no significant advantage for all the outcomes assessed including the duration of orthodontic treatment, number of routine orthodontic appliance adjustment visits, the rate of orthodontic tooth movement during the alignment and space closure stages, OIIRR, patient perception of pain and the reported need for analgesics at different time points early in treatment. Although Pavlin 2015 reported accelerated OTM during the space closure stage, Lombardo 2018 reported higher accuracy of alignment in one tooth only (maxillary incisor rotation) and Miles 2016 reported a reduced requirement for analgesics at 24 hours only after the ligation of the first aligning archwire (Miles 2016), the differences were too small to have clinical significance. Those studies were all judged to be at high risk of bias (Lombardo 2018; Miles 2016; Pavlin 2015). 

LLLT versus placebo or control during orthodontic treatment

This comparison included 10 RCTs (Abellán 2021; Alam 2019; AlSayed 2017; Caccianiga 2017; El Shehawy 2020; Farhadian 2021; Ghaffer 2022; Hasan 2022; Lalnunpuii 2020; Lo Giudice 2020), with a total of 423 participants recruited to assess the influence of LLLT on OTM. All studies were rated as having high risk of bias. The outcome from this review indicates that there is very low‐certainty evidence to suggest that the application of LLLT can reduce the duration of the alignment stage with fixed orthodontic appliances (MD ‐48.87 days, 95% CI ‐56.48 to ‐41.26) as well as the number of visits required to adjust the orthodontic appliance (median difference ‐2.25 visits, 95% CI ‐2.52 to ‐1.97). This reduction was found to be statistically significant when compared to the control groups. However, no statistical increase in the rate of (by assessing the percentage reduction in the LII) was detected in the LLLT groups during the first or the second month of the alignment stage. The meta‐analyses presented in the form of four forest plots have to be interpreted with caution due to the significant statistical and clinical heterogeneity amongst the included studies. Furthermore, it is important to note that, although the difference reported in the duration and number of visits during the alignment stage can be considered clinically significant for that specific stage of treatment, it does not necessarily reflect the same significance on the full treatment duration. 

There is little evidence to suggest that rate of OTM during space closure (en masse retraction) can be increased on the application of LLLT compared to control (right side MD 0.18 mm/month, 95% CI 0.10 to 0.26, P < 0.001; 1 study; 65 participants; very low level of certainty) (Lalnunpuii 2020). Moreover, there is little evidence to suggest that OTM during canine retraction can be increased on the application of LLLT compared to control (MD 0.01 mm/day, 95% CI 0 to 0.02; P = 0.01; 1 study, 37 participants; very low level of certainty) (Farhadian 2021). The differences reported in OTM with the LLLT seems to be clinically insignificant and do not represent the full treatment duration. 

There is very low‐certainty evidence to suggest that the application LLLT does not influence the patient's perception of pain and discomfort during orthodontic treatment. 

LED versus control during orthodontic treatment

This comparison included only two studies (both assessed as having high risk of bias) involving 80 participants to assess the influence of LED on OTM. There is very low‐certainty of the evidence to suggest that LED can significantly reduce the fixed appliance orthodontic alignment duration in the mandibular arch. However, LED did not influence the rate of canine distalisation. It is important to note that the assessed stage of orthodontic alignment does not necessarily represent the overall total orthodontic treatment duration.

There is very low‐certainty evidence to suggest that the application of LED does not influence patient perception of pain and discomfort during orthodontic treatment. 

Overall completeness and applicability of evidence

The primary objective of this review was to assess the influence of non‐surgical adjunctive interventions on the duration of orthodontic treatment and the rate of OTM. Only two studies investigated the full treatment duration (Miles 2016; Woodhouse 2015); however, most of the other included studies assessed the influence of the interventions on the duration of different stages of orthodontic treatment, representing proxy measures of treatment efficiency. It is important to note that the rate of OTM during a specified stage of orthodontic treatment does not necessarily represent the overall rate of OTM or the total orthodontic treatment duration.

Some studies assessed secondary outcomes including side effects of orthodontic treatment, e.g. OIIRR and patient‐centred outcomes including self‐reported pain and self‐reported need for analgesics. This was only reported for the light vibrational forces and was not reported for the photobiomodulation interventions. Patient‐centred outcomes were mainly assessed at different time points following the first and second visits of orthodontic treatment. These time points do not represent the full orthodontic treatment duration; however, it is reasonable to assert that this early stage of treatment is the most relevant when assessing pain and discomfort as a side effect of OTM (Ngan 1994). No other harms were noted in any of the studies.

It is important to note that there were five studies identified through our search strategy that assessed the influence of non‐surgical interventions on some of the secondary outcomes but did not report the rate of OTM or the duration of treatment; these studies were excluded from this review as they did not meet the inclusion criteria. The secondary outcome data in this review were only reported within the context of their relevance to the rate of OTM. Some of those secondary outcomes related to non‐surgical interventions, e.g patient‐centred outcomes, are addressed comprehensively in another Cochrane systematic review (Fleming 2016). 

We consider the participants in the included studies to be representative of the patient groups that would be treated in the majority of orthodontic settings in terms of age, sex, and type of malocclusion, although in some studies only the maxillary or mandibular dental arch was assessed. The severity and complexity of the malocclusion can dictate the need for dental extractions during orthodontic treatment, with some studies recruiting extraction cases and others involving non‐extraction cases or a combination of both. This can make the comparison between the reported outcomes problematic due to high levels of heterogeneity in relation to some of the outcomes.

Two main types of orthodontic appliances were used in the included studies ‐ multi‐bracket fixed orthodontic appliances and aligner therapy. Different biomechanical principles are applied with each of these orthodontic appliances. We decided to assess each type of appliance in this review separately to limit the effect of associated confounding. 

In relation to the multi‐bracket fixed appliance systems used, there was variation in slot dimensions, ligation systems and sequence of archwires. Given that there is no evidence that these variations have a significant impact on any of the investigated outcomes, we decided to collate data from these studies without the need for subgroup analysis (El‐Angbawi 2019; Fleming 2010, Papageorgiou 2014). It was deemed difficult to assess the rate of OTM in the studies that used aligners (e.g. Invisalign) for treatment due to the different methods of assessing OTM, such as the reduction of LII during treatment or use of a customised formula to assess the accuracy of tooth movement. 

Finally, there was great variation in the outcome measures that were adopted by the investigators. This was particularly marked when assessing rate of OTM in the different stages of treatment, with some studies involving study models while others used radiographs and others used customised formulas. We would suggest that uniformly applied outcomes are used when future studies are planned so that adequate comparisons between trials can be achieved.

Quality of the evidence

Limitations in study design and applicability of evidence

A total of 23 RCTs involving 1027 participants meeting the inclusion criteria were included in this review. The overall certainty of evidence is low with all the studies rated as high risk of bias except two studies that we judged to be unclear (Katchooi 2018; Woodhouse 2015). The sample size was relatively small in all studies, ranging from 13 to 33 participants per study group. Most of the studies had selection bias issues with clinicians and participants not blinded however, the detection bias in most studies was low risk.  

Several included studies recruited participants young and adults with no subgroup analysis to demonstrate if the rate OTM is similar with different age groups.  In addition, most of the included studies had two groups (control and intervention) with clear explanation about the sample size calculation, however, there were a few included studies that had 3 or 4 arms where the authors did not account for the sample size calculation with multiple comparisons required for the multiple study groups especially with longitudinal time point outcomes. Moreover, a limited number of the included studies used stratification according to bracket ligation type to ensure equal distribution of these variables in the comparison group (Kumar 2020; Lalnunpuii 2020). This stratification would require subgroup analysis; however, the authors did not account for the reduced sample size in the subgroups, which could potentially have reduced the power of the statistical tests used.

The methods of assessing OTM for specified periods or stages of treatment were not standardised in the included studies, with different criteria described. This could be a source of error that could have influenced the results. Only two of the included studies assessed the influence of the interventions on the full orthodontic treatment duration (Miles 2016; Woodhouse 2015). All the other included studies assessed stages of the orthodontic treatment ranging from a few weeks to a few months. It is important to emphasise that the outcomes from those periods of treatment do not necessarily represent the full treatment duration.

The certainty of the evidence, as assessed using GRADE, on the effectiveness of non‐surgical interventions to influence OTM was low to very low. The available evidence suggest that there is no additional benefit from the use of light vibrational forces for accelerating the rate of OTM. The limited and incomplete evidence available suggests that LLLT and LED can potentially increase the rate of OTM in the short term during the alignment stage of orthodontic treatment. It would be inappropriate to assume that the reported short‐term outcomes will be reflected in the full treatment duration. 

Potential biases in the review process

Every possible effort was made to reduce selection and reporting bias by ensuring a comprehensive search for potentially eligible studies. We used a broad search strategy with no language restrictions, and assessments were made independently by multiple authors. We are not aware of any biases in the review process. We excluded several published and ongoing studies because they were split‐mouth in design. At this time, we believe that the potential cross‐over effects in this design introduces too great a risk of bias if they were to be included in this review. The authors will continue to review this decision as evidence emerges from these ongoing studies. 

It is important to note that several studies assessed the influence of non‐surgical interventions on some of the secondary outcomes without reporting on the rate of OTM or the duration of treatment. Those studies were excluded from this review as they did not meet the inclusion criteria. This indicates that reported data for the secondary outcomes were only reported within the context of their relevance to the rate of OTM. However, some of those secondary outcomes related to non‐surgical interventions, e.g patient‐centred outcomes, were addressed comprehensively in another Cochrane systematic review (Fleming 2016). 

Agreements and disagreements with other studies or reviews

In the last decade, several systematic reviews have been conducted to assess the effectiveness of several types of  non‐surgical interventions in accelerating OTM (Baghizadeh 2020; De Almeida 2016; Gkantidis 2014; Jing 2017; Kalemaj 2015; Long 2013; Long 2015; Yi 2017). There is a lack of agreement amongst the reviews in regard to the reported effectiveness of some of the non‐surgical interventions and the certainty of the evidence assessed. 

Gkantidis 2014 reported that there is moderate to weak evidence that non‐surgical interventions (low energy laser, photobiomodulation or pulsed electromagnetic fields) can accelerate tooth movement. In contrast, De Almeida 2016 reported that there is no evidence that laser therapy can accelerate OTM. Long 2013 suggested that LLLT is safe but unable to accelerate orthodontic tooth movement; however, the same research group published another systematic review that reported that LLLT could accelerate OTM during the first three months of treatment (Long 2015). Kalemaj 2015 reported that there is some evidence that LLLT can accelerate OTM to a limited but clinically insignificant degree. In a systematic review concerning vibrational forces, Jing 2017 reported weak evidence that light vibrational forces are effective in accelerating canine retraction but not orthodontic alignment. The inconsistencies between reviews can be explained by the difference in the studies included and the certainty of evidence: Long 2013 and Gkantidis 2014 included RCTs and controlled clinical trials, while Kalemaj 2015, Jing 2017 and Baghizadeh 2020 included RCTs with split‐mouth design.

We decided to include only RCTs in this review to ensure high‐quality methodology and limit selection bias. In addition, we excluded split‐mouth design RCTs due to the potential for cross‐over effects. This explains the difference between our conclusion and the previous reviews.

A systematic review of systematic reviews was published in 2017 assessing the quality of most of the reviews published related to non‐surgical and surgical interventions for acceleration of OTM (Yi 2017). The review used the AMSTAR tool for quality assessment of the included reviews with an average score of 6.3 out of 11, indicating moderate quality of systematic review methodology. However, all the included systematic reviews assessed the quality of evidence from included studies as either low or very low using GRADE. The authors reported that LLLT is effective in promoting OTM in the short term. 

Authors' conclusions

Implications for practice.

There is low‐certainty evidence to suggest that neither the application of light vibrational forces nor photobiomodulation reduce the duration of orthodontic treatment (with fixed or removable appliances). While there is very low certainty evidence to suggest that the application of photobiomodulation (low level laser therapy and light‐emitting diode (LED)) can reduce the duration of the orthodontic alignment stage as well as the number of visits required to adjust the orthodontic appliance during the alignment stage, these results have to be interpreted with caution as it is difficult to estimate the clinical significance of this reduction on the full orthodontic treatment duration. 

Implications for research.

There is a clear need for well‐designed randomised clinical studies with standardised outcome reporting for the proposed non‐surgical adjunctive methods to accelerate tooth movement. Future studies need to have sufficient participants to detect any clinically and statistically significant differences, involve the full orthodontic treatment duration rather than just limited stages of treatment, and assess additional cost enquired to determine whether non‐surgical interventions can result in a clinically important reduction in the duration of orthodontic treatment, with minimal adverse effects.

What's new

Date	Event	Description
20 June 2023	New search has been performed	Search updated, search date 6 September 2022.
20 June 2023	New citation required and conclusions have changed	4 new studies included. There is slight change in the conclusions ‐ we have concluded "there may be benefit from photobiomodulation application for accelerating discrete treatment phases".

History

Protocol first published: Issue 12, 2013
Review first published: Issue 11, 2015

Notes

This is an update of a previously published review (El‐Angbawi 2013; El‐Angbawi 2016).

Appendices

Appendix 1. Cochrane Oral Health’s Trials Register search strategy 

Cochrane Oral Health’s Trials Register is available via the Cochrane Register of Studies. For information on how the register is compiled, see https://oralhealth.cochrane.org/trials 

1 MESH DESCRIPTOR Orthodontic Appliances EXPLODE ALL AND INREGISTER 

2 MESH DESCRIPTOR orthodontics, corrective EXPLODE ALL AND INREGISTER 

3 orthodontic* AND INREGISTER

4 ((tooth or teeth) and (move* or accelerat*)) AND INREGISTER

5 #1 or #2 or #3 or #4

6 MESH DESCRIPTOR Lasers EXPLODE ALL AND INREGISTER

7 laser* AND INREGISTER

8 MESH DESCRIPTOR Electromagnetic Radiation AND INREGISTER

9 MESH DESCRIPTOR Electromagnetic fields AND INREGISTER

10 (electromagnetic and (energ* or wave* or radiation or pulse* or field*)) AND INREGISTER

11 (electric* and (energ* or pulse* or wave* or current*)) AND INREGISTER

12 MESH DESCRIPTOR Vibration AND INREGISTER

13 vibrat* AND INREGISTER

14 MESH DESCRIPTOR Light EXPLODE ALL AND INREGISTER

15 ((light* next emit*) or LED) AND INREGISTER

16 MESH DESCRIPTOR Chewing Gum EXPLODE ALL AND INREGISTER

17 (chew* near3 gum*) AND INREGISTER

18 MESH DESCRIPTOR exercise EXPLODE ALL AND INREGISTER

19 MESH DESCRIPTOR Exercise Therapy EXPLODE ALL AND INREGISTER

20 MESH DESCRIPTOR Physical Therapy Modalities EXPLODE ALL AND INREGISTER 

21 (muscle* and (train* or exercis* or physiotherap* or physical)) AND INREGISTER

22 #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21

23 #22 AND #5 

Appendix 2.  Cochrane Central Register of Controlled Clinical Trials (CENTRAL) search strategy 

1 MESH DESCRIPTOR Orthodontic Appliances EXPLODE ALL AND CENTRAL:TARGET

2 MESH DESCRIPTOR orthodontics, corrective EXPLODE ALL AND CENTRAL:TARGET

3 orthodontic* AND CENTRAL:TARGET

4 ((tooth or teeth) and (move* or accelerat*)) AND CENTRAL:TARGET 

5 #1 or #2 or #3 or #4

6 MESH DESCRIPTOR Lasers EXPLODE ALL AND CENTRAL:TARGET

7 laser* AND CENTRAL:TARGET

8 MESH DESCRIPTOR Electromagnetic Radiation AND CENTRAL:TARGET

9 MESH DESCRIPTOR Electromagnetic fields AND CENTRAL:TARGET

10 (electromagnetic and (energ* or wave* or radiation or pulse* or field*)) AND CENTRAL:TARGET

11 (electric* and (energ* or pulse* or wave* or current*)) AND CENTRAL:TARGET

12 MESH DESCRIPTOR Vibration AND CENTRAL:TARGET

13 vibrat* AND CENTRAL:TARGET

14 MESH DESCRIPTOR Light EXPLODE ALL AND CENTRAL:TARGET

15 ((light* next emit*) or LED) AND CENTRAL:TARGET

16 MESH DESCRIPTOR Chewing Gum EXPLODE ALL AND CENTRAL:TARGET

17 (chew* near3 gum*) AND CENTRAL:TARGET

18 MESH DESCRIPTOR exercise EXPLODE ALL AND CENTRAL:TARGET

19 MESH DESCRIPTOR Exercise Therapy EXPLODE ALL AND CENTRAL:TARGET

20 MESH DESCRIPTOR Physical Therapy Modalities EXPLODE ALL AND CENTRAL:TARGET

21 (muscle* and (train* or exercis* or physiotherap* or physical)) AND CENTRAL:TARGET

22 #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21

23 #22 AND #5

Appendix 3. MEDLINE Ovid search strategy

1. exp Orthodontic appliances/ 

2. exp Orthodontics, corrective/ 

3. orthodontic$.ti,ab. 

4. ((tooth or teeth) adj5 (move$ or accelerat$)).ti,ab. 

5. or/1‐4 

6. exp Lasers/ 

7. laser$.ti,ab. 

8. Electromagnetic radiation/ 

9. Electromagnetic fields/ 

10. (electromagnetic adj3 (energ$ or wave$ or radiation or pulse$ or field$)).ti,ab.

11. (electric$ adj3 (energ$ or pulse$ or wave$ or current$)).ti,ab. 

12. Vibration/ 

13. vibrat$.ti,ab. 

14. exp Light/ 

15. ((light$ adj emit$) or LED).ti,ab. 

16. exp Chewing gum/ 

17. (chew$ adj3 gum$).ti,ab. 

18. exp exercise/ 

19. exp exercise therapy/ 

20. (muscle$ and (train$ or exercis$ or physiotherap$ or physical)).ti,ab. 

21. exp physical therapy modalities/ 

22. 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 

23. 5 and 22

The above subject search was linked with the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials in MEDLINE (as described in Lefebvre 2022, box 3c). 

1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. drug therapy.fs.
6. randomly.ab.
7. trial.ab.
8. groups.ab.
9. or/1‐8
10. exp animals/ not humans.sh.
11. 9 not 10

Appendix 4. Embase Ovid search strategy

1. Orthodontic device/ 
2. exp Orthodontics/ 
3. orthodontic$.ti,ab. 
4. ((tooth or teeth) adj5 (move$ or accelerat$)).ti,ab. 
5. or/1‐4 
6. Laser/ 
7. laser$.ti,ab. 
8. Electromagnetic radiation/ 
9. Electromagnetic field/ 
10. (electromagnetic adj3 (energ$ or wave$ or radiation or pulse$ or field$)).ti,ab.
11. (electric$ adj3 (energ$ or pulse$ or wave$ or current$)).ti,ab.
12. Vibration/ 
13. vibrat$.ti,ab. 
14. light/ 
15. ((light$ adj emit$) or LED).ti,ab. 
16. Chewing gum/ 
17. (chew$ adj3 gum$).ti,ab. 
18. exercise/ 
19. Physiotherapy/ 
20. (muscle$ adj3 (train$ or exercis$ or physiotherap$ or physical)).ti,ab. 
21. or/6‐20 
22. 5 and 21

The above subject search was linked with the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials in Embase (as described in Lefebvre 2022, box 3e). 

1. Randomized controlled trial/

2. Controlled clinical study/

3. random$.ti,ab.

4. randomization/

5. intermethod comparison/

6. placebo.ti,ab.

7. (compare or compared or comparison).ti.

8. ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab.

9. (open adj label).ti,ab.

10. ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab.

11. double blind procedure/

12. parallel group$1.ti,ab.

13. (crossover or cross over).ti,ab.

14. ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab.

15. (assigned or allocated).ti,ab.

16. (controlled adj7 (study or design or trial)).ti,ab.

17. (volunteer or volunteers).ti,ab.

18. human experiment/

19. trial.ti.

20. or/1‐19

21. random$ adj sampl$ adj7 ("cross section$" or questionnaire$1 or survey$ or database$1)).ti,ab. not (comparative study/ or controlled study/ or randomi?ed controlled.ti,ab. or randomly assigned.ti,ab.)

22. Cross‐sectional study/ not (randomized controlled trial/ or controlled clinical study/ or controlled study/ or randomi?ed controlled.ti,ab. or control group$1.ti,ab.)

23. (((case adj control$) and random$) not randomi?ed controlled).ti,ab.

24. (Systematic review not (trial or study)).ti.

25. (nonrandom$ not random$).ti,ab.

26. "Random field$".ti,ab.

27. (random cluster adj3 sampl$).ti,ab.

28. (review.ab. and review.pt.) not trial.ti.

29. "we searched".ab. and (review.ti. or review.pt.)

30. "update review".ab.

31. (databases adj4 searched).ab.

32. (rat or rats or mouse or mice or swine or porcine or murine or sheep or lambs or pigs or piglets or rabbit or rabbits or cat or cats or dog or dogs or cattle or bovine or monkey or monkeys or trout or marmoset$1).ti. and animal experiment/

33. Animal experiment/ not (human experiment/ or human/)

34. or/21‐33

35. 20 not 34

Appendix 5. LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database) search strategy

((Mh orthodontics or orthodontic$ or ortodon$) and (Mh laser or laser$ or Mh Electromagnetic radiation or Mh Electromagnetic field or electromagnet$ or Mh Vibration or vibra$ or Mh Light or light$ or LED or Mh chewing gum or "chewing gum$" or Mh exercise or "muscle train$" or exercis$ or physiotherap$))

The above subject search was linked to the Brazilian Cochrane Center search strategy for LILACs BIREME:

((Pt randomized controlled trial OR Pt controlled clinical trial OR Mh randomized controlled trials OR Mh random allocation OR Mh double‐blind method OR Mh single‐blind method) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Pt clinical trial OR Ex E05.318.760.535$ OR (Tw clin$ AND (Tw trial$ OR Tw ensa$ OR Tw estud$ OR Tw experim$ OR Tw investiga$)) OR ((Tw singl$ OR Tw simple$ OR Tw doubl$ OR Tw doble$ OR Tw duplo$ OR Tw trebl$ OR Tw trip$) AND (Tw blind$ OR Tw cego$ OR Tw ciego$ OR Tw mask$ OR Tw mascar$)) OR Mh placebos OR Tw placebo$ OR (Tw random$ OR Tw randon$ OR Tw casual$ OR Tw acaso$ OR Tw azar OR Tw aleator$) OR Mh research design) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Ct comparative study OR Ex E05.337$ OR Mh follow‐up studies OR Mh prospective studies OR Tw control$ OR Tw prospectiv$ OR Tw volunt$ OR Tw volunteer$) AND NOT (Ct animal AND NOT (Ct human and Ct animal))) [Words]

Appendix 6. Trials registries search strategies

US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) search strategy

orthodontic and acclerat* and laser 

orthodontic and move* and laser 

orthodontic and acclerat* and electromagnetic

orthodontic and move* and electromagnetic

orthodontic and acclerat* and vibration

orthodontic and move* and vibration

orthodontic and acclerat* and light

orthodontic and move* and light

orthodontic and acclerat* and LED

orthodontic and move* and LED

orthodontic and acclerat* and “chewing gum”

orthodontic and move* and “chewing gum”

orthodontic and acclerat* and “muscle training”

orthodontic and move* and “muscle training”

World Health Organization International Clinical Trials Registry Platform search strategy

orthodontic AND accelerat* AND laser OR orthodontic AND accelerat* AND electromagnetic OR orthodontic AND accelerat* AND vibration OR orthodontic AND accelerat* AND light OR orthodontic AND accelerat* AND LED OR orthodontic AND accelerat* AND “chewing gum” OR orthodontic AND accelerat* AND “muscle training”

orthodontic AND move* AND laser OR orthodontic AND move* AND electromagnetic OR orthodontic AND move* AND vibration OR orthodontic AND move* AND light OR orthodontic AND move* AND LED OR orthodontic AND move* AND “chewing gum” OR orthodontic AND move* AND “muscle training”

Appendix 7. Correspondence with Woodhouse 2015; Mr Andrew DiBiase January 2021

Hi Ahmed

I did not register it on the clinical trials website so I am not sure why it states lower incisors but I imagine this is a mistake by the person who registered the trial.  The protocol as I understood it planned to use the upper central incisors to measure OIIRR: hence the periodical radiograph was taken at the start of treatment. The upper central incisor was chosen as it is a tooth that is susceptible to root resorption and a standardised long cone PA can be more routinely taken. No further radiographs were taken beyond the 2 PAs and routine diagnostic radiographs used in orthodontics.

I hope this helps and best of luck with the SR

BW

Andrew
 

On 3 Jan 2021, at 18:38, Ahmed El‐Angbawi wrote:

Thank you for the swift reply Andrew

I noticed that in the clinical trials registry it was planned to assess OIIRR for the lower four incisors (below). Can you please kindly advise if there was a reason why the lower four incisors were not assessed for OIIRR? 

Root resorption [ Time Frame: 6‐12 months from start ]

Root length of the four lower incisor teeth will be measured from a long‐cone periapical radiograph taken at the start of treatment (R1) using digital callipers. A second periapical radiograph of the lower incisors will be taken following tooth alignment (R2). The length of the crown from the tip to the cemento‐enamel junction will also be measured at the start (C1) and end of alignment (C2). The X‐ray enlargement factor will then be calculated as C1/C2, with apical root resorption = R1‐R2 x (C1/C2)

Kind regards 

Ahmed 

From: DIBIASE, Andrew
Sent: 03 January 2021 18:29
To: Ahmed El‐Angbawi
Subject: Re: Effect of supplemental vibrational force on orthodontically induced inflammatory root resorption: A multicenter randomized clinical trial

Hi Ahmed

Good to hear from you. We measured the OIIRR from the upper right central incisor from  lone cone periapicals taken at the start of treatment and the end of alignment (ie when a 19 x 25 steel wire was placed)  using the correction method outlined by Linge L, Linge BO. Patient characteristics and treatment variables associated with apical root resorption during orthodontic treatment. AJ Orthod Dentofacial Orthop 1991;99:35‐43. whereby you measure the crown and root length on both films and correct accordingly for enlargement and foreshortening. I did all the measurements 

I hope this helps

BW

Andrew

On 3 Jan 2021, at 17:10, Ahmed El‐Angbawi wrote:

Dear Mr DiBiase 

I hope this email finds you well. 

We are currently in the process of updating the Cochrane systematic review " non‐surgical interventions for accelerating orthodontic tooth movement". Your publication named below is a key study in the review. I will be grateful if you can assist with the below information regarding your publication 

Effect of supplemental vibrational force on orthodontically induced inflammatory root resorption: A multicenter randomized clinical trial

• Which teeth were assessed for OIIRR? 

• Was there a quality assessment protocol set for the x‐rays? 

• If further x‐rays were taken to assess OIIRR?

Many thanks in advance for your cooperation.

Ahmed El‐Angbawi

Senior Clinical Lecturer & Honorary Consultant in Orthodontics
Academic Orthodontic Lead 
Division of Dentistry, University of Manchester
Manchester, M13 9PL, UK

Data and analyses

Comparison 1. Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Overall total orthodontic treatment duration: light vibrational forces vs control	2	77	Mean Difference (IV, Fixed, 95% CI)	‐0.61 [‐2.44, 1.22]
1.2 Total number of orthodontic appliance adjustment appointments: light vibrational forces vs control	2	77	Mean Difference (IV, Fixed, 95% CI)	‐0.32 [‐1.69, 1.05]
1.3 OTM early alignment (4‐6 weeks) in the form of the reduction in the LII index: light vibrational forces vs control	3	144	Mean Difference (IV, Fixed, 95% CI)	0.12 [‐1.77, 2.01]
1.4 OTM mid alignment (10‐16 weeks) in the form of the reduction in the LII index: light vibrational forces vs control	4	175	Mean Difference (IV, Fixed, 95% CI)	‐0.18 [‐1.20, 0.83]
1.5 OTM full alignment in the form of the reduction in the LII index: light vibrational forces vs control	1	54	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐7.02, 6.62]
1.6 Rate of OTM during space closure en‐masse (maxillary and mandibular arches): light vibrational forces vs control	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.6.1 Space closure en‐masse	2	81	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.08, 0.29]
1.7 Rate of OTM during space closure en‐masse (maxillary arch only): light vibrational forces vs control	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8 Rate of OTM during space closure en‐masse (mandibular arch only): light vibrational forces vs control	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.9 Rate of OTM during maxillary canine distalisation space closure: light vibrational forces vs control	2	40	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.20, 0.18]
1.10 Patient perception of pain immediately after initial wire ligation: light vibrational forces vs control	3	153	Mean Difference (IV, Fixed, 95% CI)	2.56 [‐2.35, 7.47]
1.11 Patient perception of pain after 4‐8 hours from the initial archwire ligation: light vibrational forces vs control	3	153	Mean Difference (IV, Fixed, 95% CI)	‐0.99 [‐8.83, 6.85]
1.12 Patient perception of pain after 1 day from the initial archwire ligation: light vibrational forces vs control	3	153	Mean Difference (IV, Fixed, 95% CI)	‐2.93 [‐11.25, 5.39]
1.13 Patient perception of pain after 3 days from the initial archwire ligation: light vibrational forces vs control	3	153	Mean Difference (IV, Fixed, 95% CI)	‐0.48 [‐7.13, 6.18]
1.14 Patient perception of pain after 7 days from the initial archwire ligation: light vibrational forces vs control	3	153	Mean Difference (IV, Fixed, 95% CI)	0.04 [‐2.97, 3.05]
1.15 Patients' reported need for analgesics during the first week of the initial aligning archwire: light vibrational forces vs control	2	95	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.60, 4.53]
1.16 Patient perception of pain and discomfort immediately after ligation of the second aligning archwire: light vibrational forces vs control	1	53	Mean Difference (IV, Fixed, 95% CI)	‐2.20 [‐18.49, 14.09]
1.17 Patient perception of pain after 4‐8 hours from the second aligning archwire ligation: Light vibrational forces vs control	1	53	Mean Difference (IV, Fixed, 95% CI)	10.65 [‐5.03, 26.33]
1.18 Patient perception of pain after 1 day from the second aligning archwire ligation: light vibrational forces vs control	1	53	Mean Difference (IV, Fixed, 95% CI)	18.66 [3.41, 33.91]
1.19 Patient perception of pain after 3 days from the second aligning archwire ligation: light vibrational forces vs control	1	53	Mean Difference (IV, Fixed, 95% CI)	6.47 [‐6.84, 19.78]
1.20 Patient perception of pain after 7 days from the second aligning archwire ligation: light vibrational forces vs control	1	53	Mean Difference (IV, Fixed, 95% CI)	3.63 [‐11.70, 18.96]
1.21 Patients' reported need for analgesics during the first week of the second aligning archwire: light vibrational forces vs control	1	53	Odds Ratio (M‐H, Fixed, 95% CI)	1.01 [0.32, 3.20]
1.22 Orthodontically induced inflammatory root resorption: light vibrational forces vs control	1	50	Mean Difference (IV, Fixed, 95% CI)	0.09 [‐0.35, 0.53]

1.5. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 5: OTM full alignment in the form of the reduction in the LII index: light vibrational forces vs control 

1.16. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 16: Patient perception of pain and discomfort immediately after ligation of the second aligning archwire: light vibrational forces vs control 

1.17. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 17: Patient perception of pain after 4‐8 hours from the second aligning archwire ligation: Light vibrational forces vs control 

1.19. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 19: Patient perception of pain after 3 days from the second aligning archwire ligation: light vibrational forces vs control 

1.20. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 20: Patient perception of pain after 7 days from the second aligning archwire ligation: light vibrational forces vs control 

1.21. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 21: Patients' reported need for analgesics during the first week of the second aligning archwire: light vibrational forces vs control 

1.22. Analysis.

Comparison 1: Effect of light vibrational forces as an adjunct to orthodontic fixed appliance treatment versus conventional orthodontic fixed appliance treatment (control), Outcome 22: Orthodontically induced inflammatory root resorption: light vibrational forces vs control 

Comparison 2. Effect of low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Orthodontic alignment duration: LLLT vs control	3	92	Mean Difference (IV, Fixed, 95% CI)	‐48.87 [‐56.48, ‐41.26]
2.2 Number of orthodontic appliance adjustment appointments during the alignment stage: LLLT vs control	2	125	Mean Difference (IV, Fixed, 95% CI)	‐2.25 [‐2.52, ‐1.97]
2.3 OTM early alignment  (4 weeks)  percentage reduction in the LII: LLLT vs control	2	56	Mean Difference (IV, Fixed, 95% CI)	1.63 [‐2.60, 5.86]
2.4 OTM early alignment  (8 weeks) percentage reduction in the LII: LLLT vs control	2	56	Mean Difference (IV, Fixed, 95% CI)	3.75 [‐1.74, 9.24]
2.5 Patient perception of pain during maxillary canine retraction:  LLLT vs control	1	37	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐1.87, 1.07]

2.5. Analysis.

Comparison 2: Effect of low level laser therapy (LLLT) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 5: Patient perception of pain during maxillary canine retraction:  LLLT vs control

Comparison 3. Effect of light emiting diode (LED) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Duration of orthodontic alignment stage mandibular arch: LED vs control	1	34	Mean Difference (IV, Fixed, 95% CI)	‐24.50 [‐42.45, ‐6.55]
3.2 OTM space closure canine distalisation/space closure: LED vs control	1	39	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.00, 0.02]
3.3 Patient perception of pain: LED vs control	1	39	Mean Difference (IV, Fixed, 95% CI)	0.80 [‐0.62, 2.22]

3.1. Analysis.

Comparison 3: Effect of light emiting diode (LED) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 1: Duration of orthodontic alignment stage mandibular arch: LED vs control

3.2. Analysis.

Comparison 3: Effect of light emiting diode (LED) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 2: OTM space closure canine distalisation/space closure: LED vs control

3.3. Analysis.

Comparison 3: Effect of light emiting diode (LED) as an adjunct to orthodontic appliance treatment on OTM versus conventional orthodontic appliance treatment (control), Outcome 3: Patient perception of pain: LED vs control

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abellán 2021.

Study characteristics
Methods	Study design: parallel RCT, 2 arms Setting: Teaching Dental Hospital, Universidad Complutense de Madrid (UCM), Spain Sample size calculation: by IBM SPSS Sample‐Power (v3.0) based on detecting a difference between groups of 1 mm or more in the primary outcome variable: intruded distance, assuming SD of 0.7, error a = 0.05, and statistical power of 80%. A sample of 20 participants (10 per group) was judged to be adequate, taking into account potential dropouts.
Participants	20 participants with fixed orthodontic appliance Less than 18 years of age Inclusion criteria First upper molar extruded, without curved roots Permanent dentition Presence of adjacent teeth of molar to intrude Adequate oral hygiene No previous orthodontic treatment No trauma or dental and congenital anomalies No reconstructions No periodontal disease No severe crowding on the back of the jaw or rotated teeth Alveolar bone loss < 30% Exclusion criteria  > 18 years old Diabetes mellitus, cancer, HIV Congenital craniofacial malformations Taking medications that can alter the response to orthodontic treatment (nonsteroidal anti‐inflammatory drugs) Metabolic or endocrine disorders Health conditions contraindicated for orthodontic treatment or laser treatment (pregnancy and lactation) Osteoporosis Immunological disorders Alterations of connective tissue Antibiotics use
Interventions	Experimental group: intrusion + laser Control group: intrusion Appliance: fixed appliance with TADS and elastic bands. Force 75 g Laser: low‐power diode laser (Periowave; Ondine BioPharma) emitting at a wavelength of 670 nm, with a power of 150 mW (measured with a Gentec XLP power detector in combination with a Gentec console—ONLY 2). Radiation applied through a flexible optical fibre connected to an autoclavable stainless steel handpiece designed by the user. Handpiece has a light diffuser tip configured as a periodontal probe to allow access to the periodontal pocket. The diffuser tip moved smoothly around the gum on each of the dental surfaces (distal, mesial, vestibular, and palatal) of the molar to be intruded for 3 min for each surface (total 12 min) on days 0, 1, 2, 3, 4 and 7 of the beginning of the intrusion and in each monthly follow‐up.
Outcomes	Primary Molar intrusion amount assessed by scanning days 0, 90 and 180 with an intraoral scanner (3Shape Trios) and CBCT day 0 and day 180 Secondary Root resorption assessed using CBCT day 0 and day 180 Periodontal health assessed using plaque index, probing depth, and bleeding of probing at 0, 1, 2, 3, and 6 months
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation: done using online computer software (Research Randomizer)
Allocation concealment (selection bias)	Unclear risk	No mention of allocation method
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants nor clinicians
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding of assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Unclear risk	Study registered but no access to the registration
Other bias	Unclear risk	Reliability of measurements not done

Alam 2019.

Study characteristics
Methods	Study design: parallel RCT, 4 arms Setting: Teaching Dental Hospital, Division of Orthodontics, College of Dentistry, Jouf University, Saudi Arabia Sample size calculation: power 80%, α 0.05, and effect size (d) 0.22 was used. Hence, total sample size intended was 32; each group required a minimum of 8 participants.
Participants	32 participants with fixed orthodontic appliance Age 14 to 24 years Inclusion criteria Angle class I or II or III malocclusion with ectopic maxillary canine requiring space creation or extraction of first premolar Exclusion criteria On medications such as non‐steroidal anti‐inflammatory drugs (NSAIDs), corticosteroids, bisphosphonates that disturb the bone metabolism or tooth movement Presence of parafunctional habits Temporomandibular joint (TMJ) dysfunction Craniofacial malformation Multiple missing teeth Impacted teeth Periodontally compromised
Interventions	4 groups: 2 intervention groups having LLLI (one with self ligating and the other with conventional brackets) and another 2 control groups (one with self ligating and the other with conventional brackets).  All participants had upper orthodontic fixed appliance 0.022 inch bracket slot system. Archwire sequence 0.012‐inch super‐elastic nickel‐titanium (NiTi) wire was used for alignment and levelling, which was followed by 0.014, 0.016 and 0.018 NiTi wires at 4‐week intervals between each wire. Intervention groups (LLLT) LLLT + self‐ligating brackets No LLLT + self‐ligating brackets Laser unit was a 940 nm aluminum‐gallium‐arsenide (Al‐Ga‐As) diode laser (iLase; Biolase, Irvine, CA, USA) set on continuous mode with power at 100 mW) diameter of the optical fibre tip was 0.04 cm2, the energy density was calculated to be 7.5 J/cm2 for each point, and total energy density was 75 J per tooth. Laser applied on gingival mucosa for 3 sec each on 5 points labially/buccally and palatally per tooth, starting from central incisor to the first molar. These points were mesial and distal over the cervical‐third of the root and the middle of the root and also mesial and distal over the apical‐third of the root. The fibre tip of the laser was in close but light contact with the surface of the gingival tissues and held perpendicular to the mucosa overlying the roots of teeth. Control groups: no LLLT application of any form No LLLT + self‐ligating brackets No LLLT + conventional brackets
Outcomes	Primary Rate of orthodontic teeth movement with the maxillary canine tooth aligning for 28 days. Unit of measurement not mentioned, but photos and cone beam CT used Secondary Patient perception of pain using NRS questionnaire to measure pain intensity. Participants asked to record pain after 4 hours, 24 hours, 3 days and 7 days
Notes	Study data published in 2 journal articles with conflicting information about the randomisation process
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	"...enrolled and randomly allocated to the 4 groups..." No information provided about random sequence generation. Eight participants in each group. See 'other bias' below
Allocation concealment (selection bias)	High risk	Not described, probably not done
Blinding of participants and personnel (performance bias) All outcomes	High risk	"The intervention provider and the patient were not blinded to the intervention"
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding of assessor mentioned
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts reported
Selective reporting (reporting bias)	High risk	Study not registered; no protocol published The same study outcomes were published in two separate peer reviewed journals. Some statistical analysis results were published in one article but not in the other although reporting on the same outcome.
Other bias	High risk	Poor study design; reliability of the data were not assessed.  Although the study was published in the Bangladesh Journal of Medical Science Vol. 18 No. 02 April 2019 as "randomised clinical trial", the results were also published in another journal in the same year Pain Research and Management Journal volume 2019 with authors mentioning "study was designed and conducted according to the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)"

AlSayed 2017.

Study characteristics
Methods	Study design: parallel RCT, 2 arms Setting: Teaching Dental Hospital, Department of Orthodontics at Damascus University, Syria Sample size calculation: power 80% and significance level of 0.05 to detect a 40% reduction in time to align teeth (97.2 days) with SD 82.5 days  Reliability: evaluated using intraclass correlation coefficient. 10 dental casts (of the T1 casts) were randomly chosen, and LII was re‐measured 1 month after the first measurement.
Participants	26 participants with fixed orthodontic appliance 0.022‐inch bracket slot system (MBT) Inclusion criteria Age 16 to 24 years old Moderate crowding (tooth‐size arch‐length discrepancy of 3 to 5 mm) in the anterior maxilla with LII of 7 mm or more Extraction of first maxillary premolars Feasibility of bonding brackets on all maxillary teeth No systemic diseases Good oral hygiene No previous orthodontic treatment Severe tooth displacement (e.g. ectopic canine) Those reporting the use of medications throughout the study
Interventions	All study participants had fixed orthodontic appliance treatment with bracket slot 0.022‐inch MBT prescription. Archwire sequence 0.014‐inch NiTi, 0.016 x 0.016‐inch, 0.0173 0.025‐inch NiTi, and finally 0.0193 0.025‐inch stainless steel Intervention group Laser After inserting the first archwire, a laser dose was applied using an 830‐nm wavelength laser device (CMS Dental ApS, 55 Wildersgade, 1408 Copenhagen K, Denmark) with a 2.25‐J/cm2 irradiation dose. The laser beam was applied to each root of the six maxillary incisors roots. Each root was divided into two halves: cervical and apical. The laser device tip was applied to the centre of each half, perpendicular to the root and in direct contact with the mucosa from both the buccal and palatal sides so that there were four application points for each tooth with an exposure time of 1 minute/tooth. The laser application was repeated on days 3, 7 and 14 after the first application and every 15 days starting from the second month until the levelling and the alignment stage was complete. Control group No laser application of any form
Outcomes	Primary Duration (days) of levelling and alignment of the maxillary arch measured before treatment, at 1 month, at 2 months and at the end of alignment. Treatment was considered finished when LII was less than 1 mm, indicating complete alignment of the teeth, and it was feasible to insert the final archwire passively into all brackets, indicating complete levelling of the teeth. Measurements of alignment were done using LLI done on study models from alginate impressions. Secondary Levelling and alignment improvement percentage (LAIP) of the maxillary teeth throughout the levelling and alignment stage, calculated by dividing change in LII value at the relevant timepoint by LII value at baseline.
Notes	Maxillary arch alignment only Extraction of first maxillary premolars Study duration July 2015 to March 2016
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple 2‐arm randomisation technique 1:1 Page 500: "each patient was asked to select a folded piece of paper from a box containing 26 pieces of paper on 13 of which the word ‘‘laser’’ was written; on the other 13, the word ‘‘control’’ was written"
Allocation concealment (selection bias)	Unclear risk	No measures mentioned by the authors to ensure allocation concealment. No mention if the folded piece of paper was safeguarded, e.g. stapled or tapped. "...each patient was asked to select a folded piece of paper from a box containing 26 pieces of paper on 13 of which the word ‘‘laser’’ was written; on the other 13, the word ‘‘control’’ was written"
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants or clinicians described
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding of the assessor during measurements from study models
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Low risk	RCT registered in Clinical Trials database (NCT02568436)
Other bias	Unclear risk	Control group started with high LLI compared to experimental group. Not shown if the difference was statistically significant

Caccianiga 2017.

Study characteristics
Methods	Study design: parallel RCT, 2 arms (described by trial authors as a pilot study) Setting: Department of Surgery and Translational Medicine, Section of Orthodontics, Milano‐Bicocca University, Italy Sample size calculation: none Reliability: 15 randomly selected dental casts were re‐measured by the same operator 4 weeks later. A paired sample t‐test was applied to the first and second measurements and no differences were found.
Participants	36 participants planned for fixed appliance orthodontic treatment non‐extraction Inclusion criteria Age 13 to 30 years Completely erupted mandibular teeth Angle class I malocclusion Lower 6–6 mild crowding measured on dental cast No spaces or diastema in the lower arch No ectopic teeth No treatment plan, including extractions or the use of intraoral or extraoral auxiliary device No previous orthodontic treatment
Interventions	Participants treated by single operator with 0.022‐in slot Empower self‐ligating appliances (American Orthodontics, Sheboygan, WI) and Low Profile tubes (American Orthodontics) with MBT prescription. Archwire sequence 0.014‐in thermal NiTi archwire, (Thermal‐Ti Lite, Form I; American Orthodontics) followed by 0.016‐in, 0.022‐in and 0.017 x 0.025‐in thermal NiTi archwires (Thermal‐Ti Lite, Form I; American Orthodontics). Intervention group Laser LLLT administered to test group using a diode laser emitting infrared radiation at 980 nm (Wiser; Doctor Smile–Lambda Spa, Brendola, VI). The plane wave optical fibre (AB 2799; Doctor Smile–Lambda Spa) dispensed a beam spot size of 1 cm2 and irradiation was administered by positioning the optical fibre tip along the mandibular dental arch (1.5 cm as minimum on defocalisation, as prescribed by the producer). Four dental segments (right first premolar‐canine, right lateralcentral incisors, left central‐lateral incisors, left canine‐first premolar) consecutively irradiated for 8 sec and two dental segments (right first molar‐second premolar, left second premolar‐first molar) for 9 sec, for a total of 50 sec. Procedure repeated 3 times at intervals of 2 min. All irradiations done with an output power of 1W at a continuous wave. Total energy density for entire mandibular dental arch, corresponding to an exposure time of 150 sec, was 150 J/cm2, (1 J/cm2 per second) including 27 J/cm2 for each of the two first molar‐second premolar segments and 24 J/cm2 for each of the remaining four dental segments. Intervention mentioned above every 4 weeks Control group No laser application of any form
Outcomes	Primary Duration (days) of mandibular arch levelling and alignment from T1 (before start of treatment) to T2 (end of alignment ‐ not precisely defined). Measurements of arch alignment was done using LLI on study models with digital calliper. Secondary Number of visits from T1 to T2
Notes	Mandibular arch alignment only Non‐extraction Study duration: January 2014 to March 2016
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	2‐arm simple randomisation done Page 2 "SPSS Statistics software (IBM Corporation, Armonk, NY) was used to generate an allocation sequence"
Allocation concealment (selection bias)	Unclear risk	No clear description of the allocation concealment "each subject was assigned a study number that was concealed until the date of bonding the fixed appliance"
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants or clinicians described
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding of the assessor described
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Unclear risk	Study not registered and no protocol published
Other bias	Low risk	No concerns

El Shehawy 2020.

Study characteristics
Methods	Study design: parallel RCT, 2 arms Setting: outpatient clinic, Department of Orthodontics, Faculty of Dental Medicine (Boys), Al‐AzharUniversity, Cairo, Egypt Sample size calculation: done but details not explained Reliability: 4 randomly selected dental casts were re‐measured by the same operator 4 weeks later. A paired sample t ‐test was applied to the first and second measurements and no differences were found.
Participants	30 participants planned for fixed appliance orthodontic treatment non‐extraction Inclusion criteria Complete permanent dentition (third molars not included) Moderate mandibular anterior crowding (with Little's irregularity index score greater than 4 mm) who required non‐extraction approach in the mandibular arch No tooth size, shape or root abnormalities visible on the patient's radiographic records No spaces in the mandibular arch; no blocked out tooth that did not allow for placement of the bracket at the initial bonding appointment No required management with interproximal stripping, intermaxillary elastics, open NiTi springs, and removable or extraoral devices Exclusion criteria Severe dental crowding that necessitates an extraction approach Abnormal anteroposterior and vertical relationships Cleft lip and palate, anomalies, and syndromes Previous orthodontic treatment Regular medication intake that could interfere with OTM
Interventions	All participants enrolled in the study received Roth pre‐adjusted metallic brackets (3M Unitek, Monrovia, CA) with a 0.022 ~ 0.028‐inch slot and treated with conventional NiTi archwires (Ortho Organizer, Super Elastic Nitanium Archwiress, USA) in a standardised sequence of 0.012‐, 0.014‐ and 0.016‐inch during the leveling and alignment phase for 12 weeks. Intervention group Laser "Methylene blue‐mediated PDT was delivered through gallium aluminum arsenide (Ga‐Al‐As) semiconductor diode laser (SMART PRO, LASOTRONIX, Poland) with a wavelength of 635 nm with the following set parameters: continuous mode, power output of 20 mW, fiber optic tip diameter of 2 mm, energy density of 6.5 J/cm2, exposure time of 10 sec per point resulting in dose of 0.2 J per point, 2 J per tooth and total energy of 12 J per session. The laser beam was applied to six mandibular anterior teeth where each root area was divided into 3 thirds; cervical, middle and apical. Laser was applied directly and perpendicular to target points on mesial and distal of cervical and apical thirds and on centre of middle third at 10 points, 5 facially and 5 lingually. The laser protocol was held on days 0, 3, 7 and 14 of first month and repeated for an additional 2 months. Both operator and participant wore protective eyeglasses appropriated with the utilised wavelength according to standard safety rules and all clinical procedures and laser irradiations were performed by the same investigator." Control group No laser application of any form
Outcomes	Routine orthodontic records were obtained for each participant before treatment. In addition, mandibular orthodontic study models and intraoral photographs were obtained before and at every 4‐week interval during observation period of the study. Study casts were fabricated at T0 (before treatment), T1 (after 4 weeks), T2 (after 8 weeks) and T3 (after 12 weeks) intervals.  Primary Difference in reduction in LII and percentage change in the LII between the study groups through T1‐T2‐T3 Secondary: none
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation ‐ "allocation ratio of 1:1...clinical assistants arbitrarily allocated patients into two groups with 15 patients each, using a computerised simple generated randomisation plan via an online software (http://www.graphpad com/quickcalcs/index.com)".
Allocation concealment (selection bias)	High risk	Allocation not concealed ‐ "clinical assistants arbitrarily allocated patients into two groups with 15 patients each"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were not blinded to the intervention.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Single assessor who was blinded to study groups. "LII scores by the same examiner, who was unaware about the nature of the studied groups"
Incomplete outcome data (attrition bias) All outcomes	High risk	The authors did not use intention‐to‐treat analysis with 4/30 dropouts.
Selective reporting (reporting bias)	Low risk	Study registered on ClinicalTrials.gov (NCT04376164)
Other bias	Low risk	None

Farhadian 2021.

Study characteristics
Methods	Study design: parallel RCT, 3 arms  Setting: Orthodontics Department, Hamadan University of Medical Sciences, United Arab Emirates Sample size calculation: based on smallest difference in OTM mean rate between groups being about 0.014 mm/day or 0.42 mm/month, number of participants needed for 80% power was 18. Reliability: measurements carried out by two observers with high inter‐examiner correlation (intraclass correlation coefficient 0.97)
Participants	60 participants were recruited. Inclusion criteria Patients scheduled for fixed orthodontic treatment of the upper arch with bilateral or unilateral extraction of the maxillary first premolar, followed by canine retraction Patients should have their teeth extracted at least three months before the beginning of canine retraction  Age range from 15 to 30 years Exclusion criteria Inappropriate periodontal health History of previous orthodontic treatment Systemic diseases that could affect the bone structure or density  Long‐term intake of non‐steroidal anti‐inflammatory drugs and hormonal supplements Pregnancy and breastfeeding Severe canine root dilacerations
Interventions	All participants enroled in the study received MBT system brackets with 0.022 ‐0.028‐inch slots (Ortho Technology, Lutz, USA) or Roth system with 0.018 to 0.030‐inch slots (Dentaurum, Ispringen, Germany) based on clinician preference.  "After completion of levelling and alignment, a 0.019 x 0.025‐inch stainless steel wire (Dentaurum, Ispringen, Germany) for participants with MBT bracket system and 0.016 _ 0.022‐inch stainless steel wire (Dentaurum, Ispringen, Germany) for participants with Roth system was used for canine retraction phase. " "A 6‐mm nickel‐titanium closed‐coil spring (Ortho Technology, Lutz, USA) was used for canine retraction. Springs were activated using a ligature wire to exert a force of 150 g. The force was adjusted at each visit. The anchorage was reinforced by transpalatal arch or bonding maxillary second molars, if necessary. " Intervention groups  Laser group LLLT was performed using a Cheese II dental diode laser device (Wuhan Gigaa Optronics Technology Corporation, Wuhan, China). "Ga Al As diode laser was used with a wavelength of 810 nm and a power of 100 mW. Laser tip diameter was 3.1 mm, and energy density was 4 j/cm2. LLLT was performed on days 0 (at the beginning of canine retraction), 3, 30 and 60. The laser was irradiated to 3 points on the buccal and 3 points on the canine's palatal surface (cervical, mid‐root and apical), 3 seconds each point." LED group An intraoral LED device named Biolight, similar to Ortho‐pulse, with a wavelength of 640 nm, energy density of 10 j/cm2, and 40 mW/cm2 power density was used. The inner part of the device has 2 pairs of diodes bilaterally located, irradiating the buccal surface of the canine and extraction site. At the beginning of canine retraction, participants were educated to use the device for maxillary dental arch 5 min per day. Control group Placebo, no laser application using a coated light cure device
Outcomes	Rate of canine retraction and canine rotation  T1‐T4 monthly Alginate impressions were taken monthly during canine retraction.  Alginate impressions were made for each participant at baseline and monthly thereafter until the end of canine retraction. The obtained models were scanned with an Emerald scanner (Planmeca, Helsinki, Finland), and 3D models were prepared for each participant. "The measurements of canine retraction and canine rotation were performed by Dolphin Imaging software version 11.9 (Patterson Dental Supply, Chatsworth, USA). At first, 3D models were oriented alike. Midpalatal raphe (MPR) was drawn as a reference line, and then the rugae line (RL) was drawn perpendicular to MPR from the medial end of the third palatal rugae. The canine retraction was measured by the distance from the tip of the canine to RL in millimetres at different time intervals. The angle between the line connecting the mesial and distal edges of canine and the MPR in occlusal view was considered as canine rotation." Pain perception  Patient‐centred outcomes were recorded with a modified McGill pain questionnaire, along with a VAS. In the first session, all participants were given the questionnaire and asked to complete and return it at the next appointment. The questionnaire included questions about the onset of pain, description, locality, duration, intensity, triggers and analgesic consumption following orthodontic appliance placement.
Notes	It is not clear if questionnaire was done monthly or just once.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Someone outside the research team performed the randomisation." Not clear how was this done.  "...allocated to three groups using the stratified block randomization method..."
Allocation concealment (selection bias)	Low risk	Therapeutic interventions were placed in opaque envelopes.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo was used "using a coated light cure device".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	4 dropouts. No account for the dropouts. No intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	Study registered on the Iranian Registry of Clinical Trials, www.irct.ir (IRCT20120220009086N4)
Other bias	High risk	Study described the block randomisation stratification was done based on slot size; however, later the text states that this was done according to clinician preference.

Ghaffer 2022.

Study characteristics
Methods	Study design: parallel RCT, 2 arms, 1:1 allocation ratio Setting: Orthodontic Department, Faculty of Dentistry, Ain‐Shams University, Cairo, Egypt Sample size calculation: yes, 13 per group Reliability: strong ‐ ICC from 0.825 to 0.924 and 0.806 to 0.914 for intra‐ and inter‐examiner agreements, respectively
Participants	32 females (mean age 21.5 ± 3.5 years) with mandibular anterior crowding. Preoperative LII mean of 5.85 ± 1.75 mm and 6.4 ± 2.7 mm for intervention and control groups, respectively (no statistically significant difference) Inclusion criteria Female, 18 to 25 years Fully erupted permanent dentition Angle Class I malocclusion Little's irregularity index (LII) from 4 to 10 mm Good oral and general health Exclusion criteria Pregnancy Systemic disease/condition Skeletal discrepancy in any of three planes Extracted/missing/badly decayed permanent teeth (excluding third molars) History of orthodontic treatment Treatment plan involving mandibular extractions Spacing in the mandibular arch Impediment to bracket placement on the mandibular anterior teeth
Interventions	2 groups. Both had fixed orthodontic appliance (0.022‐inch Roth Mini Diamond). 0.014‐inch copper‐nickel‐titanium wire inserted immediately after bonding followed by 0.016‐inch copper‐nickel‐titanium wire, 0.016 × 0.022‐inch NiTi then 0.017 × 0.025‐inch stainless steel wire after alignment completion. Intervention group Low‐level laser therapy (LLLT) ‐ In‐Ga‐As laser applied to mandibular anterior segment on days 3, 7 and 14, at 1 month and then every 2 weeks until completion of levelling and alignment Control group  No adjunct to orthodontic treatment
Outcomes	Primary Overall levelling and alignment time (OLAT) of mandibular anterior crowding (digital models used to monitor changes in LII) at day 3, weeks 1, 2, 4, 6, 8, 10, 12 and 14 Secondary Alignment improvement percentage at day 3, weeks 1, 2, 4, 6, 8, 10, 12 and 14 Pain in the 7 days after initial archwire placement (assessed by VAS questionnaires) Adverse effects were also mentioned.
Notes	"The study methodology was approved by the Ethical Committee review board at the Faculty of Dentistry, Ain Shams University (FDASU‐RecM071403)."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation: computer‐generated random list, no block randomisation. "Thirty‐two patients were randomized in a 1:1 ratio to laser or control groups."  "A generated randomization sequence was prepared using Microsoft Excel software (Redmond, Washington, USA). The first 16 random numbers were assigned to the intervention group while the others were assigned to the control..."
Allocation concealment (selection bias)	Low risk	1:1 allocation ratio "...Each number was placed in a sealed opaque envelope. Envelopes and the generated sequence were held by the department secretary."
Blinding of participants and personnel (performance bias) All outcomes	High risk	"Blinding of the patient and operator was not applicable due to the nature of this study."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"...data concealment and blinding of the outcome assessor and the statistician were established to minimize possible risk of bias."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	2 participants not included in analysis ‐ 1 from intervention group (missed several appointments) and 1 from control group (removed fixed appliance for wedding)
Selective reporting (reporting bias)	Unclear risk	Study not registered. No protocol published.
Other bias	Low risk	No other potential biases identified

Hasan 2022.

Study characteristics
Methods	Study design: parallel RCT, 3 arms Setting: Department of Orthodontics and Dentofacial Orthopedics and the Laser Research Unit of Damascus University Sample size calculation: using G*Power 3.1.9.2 software (University of Kiel, Germany) with level of significance set at 0.05, and statistical power set at 90%, 13 and 12 participants in each group were needed for the "treatment time'' and "overbite'' variables, respectively. In order to compensate for dropout, one was added to each group (i.e. 14), with a total required sample size of 42 Reliability: lateral cephalometric radiograph measurement. ICC ranged from 0.970 to 0.999. Paired‐sample t‐tests showed that there were no significant differences between the two assessment times (P > 0.05).
Participants	42 participants were recruited. Inclusion criteria Between 8 and 10 years of age Fully erupted upper and lower permanent incisors Class I or class II skeletal A 1 mm (minimum) anterior open bite No previous orthodontic treatment Good oral health Exclusion criteria Unilateral or bilateral crossbite, craniofacial syndromes, systemic diseases or previous facial traumas
Interventions	Three groups with a total of 42 students  Intervention group with bite blocks  The fixed posterior bite block (FPBB) used was a modification of the posterior bite block presented by Turkkahraman and Cetin. This device consisted of the transpalatal arch that connected two acrylic blocks. Intervention group with bite blocks and laser  FPBB as above. Gallium aluminum arse‐nide (Ga‐Al‐As) laser with a continuous wavelength of 808 nm applied on first day and on days 3, 7 and 14 of the first month, then every 15 days until end of treatment. Irradiation parameters of the LLL standardised throughout treatment as power of 250 MW, energy at 4 J, and application time 16 sec per point. Control group No intervention. Monitored for 9 months
Outcomes	Duration taken to correct anterior open bite. Active treatment period ended when a positive overbite of 1 to 2 mm achieved Skeletal and dental changes from lateral cephalometric radiographs
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using mini‐tab software
Allocation concealment (selection bias)	Low risk	The allocation sequence was concealed using opaque numbered and sealed envelopes. To prevent subversion of the allocation sequence, the name and the date of birth of each participant were written on the envelope, and these data were transferred onto the allocation card inside each envelope. Corresponding envelopes were only opened after completing all baseline assessments.
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of clinicians or participants
Blinding of outcome assessment (detection bias) All outcomes	High risk	No mention of blinding assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Low risk	RCT registered in Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001740189)
Other bias	Low risk	None

Katchooi 2018.

Study characteristics
Methods	Study design: parallel RCT, 2 arms Setting: private practice in North America. Two centres (Vancouver and Seattle) Sample size calculation: "power calculations were a 99% completion rate in patients with an active device, compared with a 50% completion rate with the control device. These estimates indicated that 12 subjects were required in each arm." A 1.5‐mm difference in LII between test and control groups was considered clinically meaningful. Reliability: error analysis showed that ICC was 0.98 for rater 1 (95% CI 0.93 to 0.99), 0.96 for rater 2 (95% CI 0.87 to 0.99) and ICC for average assessments between raters was 0.94 (95% CI 0.80 to 0.98), indicating no significant intra‐rater and inter‐rater difference.
Participants	27 orthodontic patients who were beginning Invisalign (Align Technology, San Jose, Calif) Inclusion criteria Adults (18 years or older) with malocclusions whose treatment involved fewer than 25 sets of aligners Exclusion criteria No significant anteroposterior or transverse movements were planned, e.g correction from Class II to Class I molar relationships Patients whose treatment plans included correction of posterior crossbites People with systemic diseases or syndromes, a history or current use of bisphosphonates, current use of prostaglandin inhibitors, generalised moderate to severe periodontitis, active oral hard or soft tissue lesions
Interventions	All study participants received Invisalign (Align Technology, San Jose, California). The aligners were fabricated using the usual approach and prescription of the treating orthodontist, with respect to sequencing of treatment, use of attachments or other treatment features, use of interproximal reduction, and so on. Tooth movement was limited to no more than 0.25 mm per aligner. Compliance in groups A and B (active and control arms) was monitored using 3 methods: (1) self reported data from questionnaires, (2) objective wear time of the aligners by the blue‐dot indicators, and (3) AcceleDent use time obtained from the device. Intervention group AcceleDent Aura device vibration appliance 30 Hz and 0.25 N for 20 min per day Control group No vibration appliance
Outcomes	Primary outcome Number of participants who are able to successfully complete a set of aligners Secondary outcomes Reduction in LII in the upper and lower arches Participant pain experience. Two time points (during first and middle aligners) Quality of life questionnaire (completed at 3 time points: immediately after distribution of first aligner, at the midpoint of treatment and at study completion visit)
Notes	Orthodontic aligners Non‐extraction
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Done: 2‐arm block stratified randomisation scheme of 2 was used in this study with stratification based on sex and age. Page 340 "The study statistician created the randomisation list by using R software (version 3.1.1; R Foundation for Statistical Computing, Vienna, Austria)".
Allocation concealment (selection bias)	Low risk	Remote allocation. A randomisation chart was kept at the University of Washington, at the time of enrolment, the orthodontist contacted the study coordinator by phone or text to receive the assignment based on age and sex.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Clinician was blinded. Participants were blinded as the control group had an inactive Aura appliance.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigator and statistician were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 exclusion. Intention‐to‐treat analysis as well as per‐protocol analysis
Selective reporting (reporting bias)	Low risk	Study registered in clinical trial.gov (clinicaltrials.gov/ct2/show/NCT02438280)
Other bias	Unclear risk	Study funded by Acceldent but results did not favour the Aura appliance. Study registered as a pilot study

Kumar 2020.

Study characteristics
Methods	Study design: RCT, multi‐arm, single‐centre, with an allocation ratio of 1:1:1.32 Setting: Department of Orthodontics and Dentofacial Orthopaedics in a nationally accredited dental college, India Sample size calculation: "...similar study on the rate of orthodontic tooth movement was conducted in the department, which was a 2‐arm parallel RCT with an equal allocation ratio. The sample size estimation for that study yielded a sample size of 17 participants per group (minimum power of 80% and an α error of 0.05 and Cohen's effect size of 0.8). By designing the present trial as a multiple arm trial, we can have a reduction of 25% in the sample size. Keeping that in mind a sample size of 20 was chosen for the experimental groups and 25 for the control group keeping the allocation ratio of 1:1:1.32 for the multi‐arm trial" Reliability: 20 randomly selected participants (10 from each group) were re‐measured by the same assessor after 2 weeks for repeatability and re‐test reliability. Intraclass coefficient was 0.88 and standard error of the mean was tabulated using paired t‐test; the findings were not statistically significant.
Participants	65 patients in fixed orthodontic appliance treatment   Inclusion criteria Age group of 13–20 years With permanent dentition LII of < 5 mm Extraction of all first bicuspids as a treatment plan Periodontally sound dentition Good general health and not under any medication (acetylsalicylic acid [ASA] or nonsteroidal anti‐inflammatory drugs [NSAIDs]) FMA between 20–25 Exclusion criteria Orthognathic surgery as treatment plan History of systemic illness (affecting the calcium metabolism, or any other causing the patient to take any medication which may alter the rate of tooth movement) Periodontally compromised dentition; congenital orofacial deformity Previous history of orthodontic therapy
Interventions	All participants in the trial were treated by a single orthodontist and in accordance with the MBT treatment philosophy. In total, 150 g of force was used for the en masse closure. Participants were randomly allocated to one of three groups. Group 1: passive self‐ligating brackets (Smartclip SL3 3M Unitek 0.02200 Slot, MBT prescription) treated using low‐frequency vibrations Group 2: conventional MBT brackets (Gemini 3M Unitek 0.02200 Slot, MBT prescription) treated using low‐frequency vibrations Group 3: conventional MBT brackets (Gemini 3M Unitek 0.02200 Slot, MBT prescription) treated without using low‐frequency vibrations Vibration device  The low‐frequency vibrations were provided by a custom‐made vibratory device. The device was adjusted to produce a frequency of 30 Hz in the mouthpiece. The participants were instructed to us the device 20 min daily.
Outcomes	Primary Rate of space closure (mm/months) Measurements on digital models were made before, at the beginning of space closure and at the end of space closure. Three‐dimensional scanning of plaster models was performed using White light technology (Solutionix C500) with a 3D reverse modelling software programme.  Perpendicular lines were drawn towards the distal surface of canine to the mesial surface of the second premolar in the pre‐retraction model.
Notes	National Trial Registry (CTRI/2018/04/013009) We contacted the trial authors as the SEs presented in the publication were larger than the SDs (which cannot be accurate, given that SE = SD/sqroot (n)). We wondered if the SE and SD column headings had been inverted, but even if this were the case, the numbers still did not add up; however, the column headed SE provided numbers that would be sensible as SDs. We contacted the trial author who replied that the SDs in the paper were accurate and reflect the homogeneity in the data. We conducted sensitivity analysis as we still had concerns about the data. As a consequence of this, we opted to present the meta‐analysis excluding Kumar.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was carried out using a computer‐generated random allocation sequence"
Allocation concealment (selection bias)	Unclear risk	No enough information provided about the concealment process. "The sequences were concealed and were chosen by the patient".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding of the participants and the primary investigator was not possible due to the nature of the trial.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Only the data analyser was blinded to the groups and the digital models presented were coded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	High risk	Registered at the National Trial Registry (CTRI/2018/04/013009) 1) registration retrospective 2) age inclusion is different (17‐20 years) 3) Sample size calculation was only 30
Other bias	Low risk	None

Lalnunpuii 2020.

Study characteristics
Methods	Study design: RCT multi‐arm, single‐centre, with an allocation ratio of 1:1:1.32 Setting: Institutional Department of Orthodontics and Dentofacial Orthopaedics  Sample size calculation: based on a previous study (minimum power of 80%, error of 0.05 and Cohen's effect size of 0.8). A sample size of 20 was chosen for experimental groups and 25 for control group, keeping the allocation ratio of 1:1:1.32 for the multi‐arm trial. Reliability: 20 randomly selected participants (10 from each group) were re‐measured by the same assessor after 2 weeks for repeatability and re‐test reliability. Intraclass coefficient was 0.88 and standard error of the mean was tabulated using paired t‐test: the findings were not statistically significant.
Participants	65 patients in fixed orthodontic appliance treatment   Inclusion criteria 13 to 20 years of age Permanent dentition Little's Irregularity Index  of < 5 mm Extraction of all first bicuspid as a treatment plan Periodontally sound dentition Sound general health and not under any medication (ASA I) Frankfurt mandibular angle (FMA) between 20–25 degrees  Exclusion criteria Orthognathic surgery as treatment plan History of systemic illness (systemic illnesses primarily affecting the calcium metabolism, or any other due to which the patient might be on any medication that may alter the rate of tooth movement) Periodontally compromised dentition Congenital orofacial deformity Previous history of orthodontic therapy Little's Irregularity Index > 5 mm
Interventions	All participants in the trial were treated by a single orthodontist using preadjusted MBT brackets system. In total, 150 g of force was used for the en masse closure (active Tied Back and en‐mass retraction). Extraction of all first bicuspids in the three groups was done prior to levelling and alignment by the same surgeon. Conventional anchorage (second molar banding and cross archwire stabilisation) was used for the three groups. All participants were instructed not to take any NSAIDs during the course of space closure and inform the primary investigator if a need arose for any other medication before taking the medication. Participants were randomly allocated to one of three groups. Group 1: passive self‐ligating brackets (Smartclip SL3 3M Unitek 0.02200 Slot, MBT prescription) treated using low‐frequency vibrations Group 2: conventional MBT brackets (Gemini 3M Unitek 0.02200 Slot, MBT prescription) treated using low‐frequency vibrations Group 3: conventional MBT brackets (Gemini 3M Unitek 0.02200 Slot, MBT prescription) treated without using low‐frequency vibrations Laser device  Laser device used was a 658 nm (Aluminium Gallium Arsenide) Semiconductor Diode laser (The Silberbauer CL mini 8‐658 EN 60601‐1‐2:2007‐07, Vienna, Austria, EU). "Laser parameters used in the trial: active medium – Aluminium Gallium Arsenide; emission type – continuous; wavelength – 658 nm; dose of irradiation – 2.29 J/cm2; energy/point – 2.2 J; output – 8mW; exposure time/point – 10 s; application – direct contact; sessions – first month, 4 times (day 0, 3, 7, 14), from second month, every 15th day; laser classification – class 2M." Two irradiations were done both buccally and palatally/lingually from canine to canine. To ensure complete irradiation of the periodontium, the protocol was: 2 doses – cervical third (1 mesial/1 distal); 2 doses – apical third (1 mesial/1 distal); 1 dose – centre of the root. Similar process repeated for the palatal/lingual side. The tip was held in contact with the tissue during application. This procedure was followed for all subsequent appointments.
Outcomes	Primary Rate of space closure (mm/months) Measurements on digital models were made before, at the beginning of space closure and at the end of space closure. Three‐dimensional scanning of plaster models was performed using White light technology (Solutionix C500) with a 3D reverse modelling software programme. The mid‐palatine line was used as a reference for measurement of available space, which was drawn in the software. Perpendicular lines were drawn towards the distal surface of canine to the mesial surface of the second premolar in the pre‐retraction model.  The average monthly rate of space closure was calculated as available extraction space/total number of days 28 days.
Notes	National Trial Registry (CTRI/2018/04/013156)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was carried out using a computer‐generated random allocation sequence" to ensure equivalent distribution amongst the 3 groups. The primary investigator had no role in the randomisation process.
Allocation concealment (selection bias)	Unclear risk	Not enough information provided about the concealment process. The authors mentioned that the allocation was concealed but did not describe the details "sequences were concealed and were chosen by the patient".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding of the participants and the primary investigator was not possible due to the nature of the trial.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Only the data analyst was blinded to the groups and the digital models presented were coded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	High risk	National Trial Registry (CTRI/2018/04/013156) ‐ registration retrospective, different age inclusion criteria (17‐30 years), sample size calculation only 30
Other bias	Low risk	No concerns

Lo Giudice 2020.

Study characteristics
Methods	Study design: RCT (1:1), single‐operator  Setting: an orthodontic private clinic in Bergamo, Italy Sample size calculation: a minimum sample size of 80 participants (40 for each group) was considered to obtain 90% power at a 95% CI to demonstrate a difference of 56 days in treatment time between PBM and control groups Reliability: 20 dental casts were randomly selected and remeasured 4 weeks later. A paired sample t‐test was applied to the first and second measurements and no differences were found. All measurements were done by one calibrated operator.
Participants	100 orthodontic patients Age between 13 and 30 years Permanent mandibular dentition Angle class I malocclusion Lower 6–6 mild crowding measured on dental cast No diastema or spaces in the lower arch No ectopic teeth No extractions required or intraoral or extraoral auxiliary devices No previous orthodontic treatment
Interventions	Both groups used the Empower self‐ligating appliance (American Orthodontics, Sheboygan, WI) with 0.022‐in slot and MBT prescription. The arch‐wire sequence included 0.014‐in thermal NiTi arch‐wire followed by 0.016 x 0.022‐in and 0.019 x 0.025‐in thermal NiTi archwires (Thermal‐Ti Lite, Form I; American Orthodontics). Review visits were scheduled at 28‐day intervals to check clinical progress and adjust the appliance if necessary by a single operator.  Intervention group  "Photobiomodulation (PBM) was administered to the PBM group using the ATP38 (Biotech Dental, Alle´e de Craponne, Salon de Provence, France). This device features a multi‐panel system emitting cold polychromatic lights with a combination of wavelengths from 450 to 835 nm depending on the field of action.  The module provided 6 min of irradiation producing 48 J/cm2 of fluency, calculated as the sum of the fluency produced by each light source (16 J/cm2) multiplied for the three active panels." A total duration of 18 min and 144 J/cm2 of fluency administered (i.e. 48 J/cm2 x 3 stages).  Each PBM session was performed every 14 days, including the date of bracket bonding, up to the end of the alignment stage. Thus, the fluency administered to participants was 288 J/cm2 per month (144 J/cm2 x 2 sessions). Control group  No PBM exposure
Outcomes	Primary Assessment of dental alignment treatment time A digital calliper (Absolute Digimatic IP67; Mitutoyo Europe GMBH) was used to quantify the Little’s irregularity index in the lower arch (6–6) on the pretreatment (T0) dental casts only. The assessment of dental alignment (T2) was based on the visual examination of correction of the 11 mandibular interproximal contacts. The date of appliance bonding (T1) and the date when complete resolution of crowding was established (T2) were recorded, and alignment treatment time was defined in days as T2–T1. Secondary None
Notes	Authors mentioned that randomisation was stratified according to sex and amount of crowding; however, the ratio of F:M was not kept equal.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"a randomized balanced block protocol using sex and the amount of crowding as stratification factors. The SPSS Statistics software (IBM Corporation, Armonk, New York) was used to generate the allocation sequence"
Allocation concealment (selection bias)	Low risk	"Assignments were enclosed in sequentially numbered, sealed, and opaque envelopes and were unveiled the date of bonding the fixed appliance".
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants or clinicians
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The assessment of dental alignment and the relative data registration were entrusted to one expert operator (M.B.) who was unaware of whether the subjects being assessed were within the PBM or control groups".
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropout: 7 participants from intervention group and 4 from control group. No Intention‐to‐treat analysis
Selective reporting (reporting bias)	High risk	The study was not registered. No protocol published
Other bias	Low risk	Study authors stated that randomisation was stratified according to sex and amount of crowding, but the ratio of F:M was not kept equal. This puts a question mark over how the stratification was done.

Lombardo 2018.

Study characteristics
Methods	Study design: parallel RCT, 3 arms Setting: University of Ferrara Postgraduate School of Orthodontics clinic Sample size calculation: "for comparison of three parallel groups via one‐way analysis of variance (ANOVA) and to achieve a type 1 error with α = 0.05 (5 per cent) and objective power 0.8 (80 per cent)—and therefore a type 2 error of 20 per cent—a minimum of 79 teeth for each tooth per arch would be necessary. Considering that the least numerous tooth type is the canine—two per arch in each patient the minimum number of patients to be recruited was 40, which was increased to 45 to take into account a possible dropout rate of 10 per cent." Reliability: "one month after completion of the analysis of all 270 arches, a random sample of 28.8 per cent of the total sample. Dahlberg’s D was calculated to evaluate the random error, and Student’s t‐test for dependent samples to determine whether or not there was any systematic error." Measurement analysis for paired samples confirmed the absence of systematic error in the measurements of MD tip, VL tip, and rotation.
Participants	Orthodontic patients who were beginning their aligners treatment with the sole aim of correcting dental alignment Inclusion criteria Permanent dentition Age between 14 and 50 years Complete dentition, or at most 1 missing tooth per quadrant (excluding third molars) No supernumerary teeth No tooth shape anomalies No tooth rotation > 35° No diastema > 5 mm Crowding < 5 mm per arch Exlsion criteria Systemic pathologies Ongoing pharmacological treatment able to influence orthodontic movement (e.g. prostaglandin inhibitors or biphosphonates) Active periodontal disease Need for treatment for extraction space closure, distalisation, or sagittal correction
Interventions	"Treatment staging, i.e. maximum movement planned for each tooth per aligner, was as follows: up to 2‐degree rotation, 2.5‐degree each labio lingual and mesiodistal tip, and 0.2‐mm linear displacement. No auxiliaries of any kind (intra‐oral elastics, buttons, chains, etc) were prescribed, but the system attachments (Grip Points) were used, in addition to anterior and/or posterior interproximal reduction (IPR). The maximum IPR included in the prescription was 0.3 mm per interproximal space, from the mesial sides of the second premolar to the mesial side of the opposite second premolar. The maximum total IPR planned was 2 mm per arch." Group A: conventional protocol with aligners replaced every 14 days Group B: conventional protocol with aligners replaced every 14 days, and use of a low‐frequency vibration device (AcceleDent; OrthoAccel Technologies, Houston, Texas, USA) for 20 min per day throughout treatment Group C: 7‐day aligners replacement protocol, and use of a low‐frequency vibration device (AcceleDent; OrthoAccel Technologies, Houston, Texas, USA) for 20 min per day throughout treatment "All patients were instructed to wear their aligners for 22 hours per day, taking them out only during meals and oral hygiene procedures. All patients were examined at monthly check‐ups until completion of aligner treatment. During these monthly check‐ups, compliance with the vibration protocol was checked via the data recorded on their AcceleDent device. Patients who failed to reach the target 20 minutes were verbally motivated to do so."
Outcomes	Absolute value of prescription, i.e. difference between ‘ideal outcome’ and ‘pre‐treatment’ measurements, as a measure of the degree of planned movement (prescription = ideal outcome/pre‐treatment) Absolute value of imprecision, i.e. difference between ‘ideal’ and ‘post‐treatment’ outcomes, as a measure of the degree to which the movement achieved differed from the planned movement (imprecision = ideal outcome/post‐treatment) To determine the degree of tooth movement achieved with respect to the prescription, the following formula was applied to each movement of each tooth: accuracy = 1 ‐ imprecision/prescription values Prescription and imprecision values were categorised according to tooth types (i.e. upper incisors, upper canines, upper premolars, upper molars, lower incisors, lower canines, lower premolars, lower molars) and type of movement (mesiodistal tipping, vestibulolingual tipping, and rotation). Movements with a prescription of less than 2 degrees (determined a priori) were excluded from the analysis.
Notes	Randomisation was done per participant, but statistical analysis was done per tooth.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	3‐arm block randomisation to ensure equal number of participants in each study group. Page 2 "Stata statistical software (StataCorp LLC, College Station, Texas, USA) was used to randomly allocate recruited patients to one of the three treatment arms".
Allocation concealment (selection bias)	Unclear risk	No clear description of the allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and clinicians were not blinded. This study used removable orthodontic appliance, so compliance was essential; if the participants are not blinded that can lead to performance bias.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The investigator was blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Low risk	Study registered in German Clinical Trials Register and all outcomes reported
Other bias	Unclear risk	"This study was supported by a research grant from the OrthoAccel Technologies, Inc. [(OATI), Bellaire, Texas]; the company was permitted to review this manuscript, but the right to a final decision on the content was retained exclusively by the authors."

Miles 2012.

Study characteristics
Methods	Study design: parallel RCT, 2 arms Setting: private practice, Pennsylvania, United States of America Sample size calculation: calculated as 90% at 0.05 level to detect 20% faster alignment and reduction in irregularity
Participants	66 participants with fixed orthodontic appliance 0.018 inch bracket slot system Age 11 to 15 years old Non‐extraction treatment plan in the lower arch No impacted or unerupted teeth Participants living close to the orthodontic practice
Interventions	Initial alignment of the lower anterior teeth using 0.018 x 0.025‐inch bracket slot system brackets and 0.014‐inch nickel titanium arch wire for 10 weeks. Intervention Vibration appliance (Tooth Masseuse), which provided a vibrational frequency of 11 Hz and 0.06N (~6.1 g), applied immediately after the initial arch wire was placed, to accelerate the alignment of the mandibular teeth. Participants instructed to use vibrational appliance daily for 20 minutes each session. Control No vibration appliance
Outcomes	Improvement in alignment of mandibular teeth measured using LII at 4 time points (0, 5, 8 and 10 weeks) Pain and discomfort measured on a VAS at 5 time points (0, 6‐8 hours, 1 day, 3 days and 7 days)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly allocated in blocks of 6 as mentioned in page 214 "randomly assigned in blocks of six"
Allocation concealment (selection bias)	Unclear risk	No mention of allocation method
Blinding of participants and personnel (performance bias) All outcomes	High risk	Clinician and investigator blinded but not the participants as mentioned in page 216: "The clinician was blinded to the study participants at all appointments. Identification numbers were assigned to the models prior to the measurements to ensure blinding". Lack of participant blinding could have influenced their scoring on a VAS for discomfort.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded during assessment, as mentioned on page 216: "Identification numbers were assigned to the models prior to the measurements to ensure blinding"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Dropouts: 2 out of 66 participants did not complete the trial. No mention of how missing data from participants who dropped out were dealt with, e.g. intention‐to‐treat analysis. We emailed study authors but received no response.
Selective reporting (reporting bias)	Unclear risk	No protocol published nor was the study registered Although planned outcomes were reported, neither the P value for statistical testing of data nor the confidence intervals were reported.
Other bias	Low risk	None

Miles 2016.

Study characteristics
Methods	Study design: 2‐arm parallel RCT Setting: private practice in Australia Sample size calculation: "a power analysis based on the arch perimeter data from an unpublished study from the University of Texas Health Science Center at San Antonio (means, 1.32 mm per week [SD, 1] vs 2.71 mm per week [SD, 1.42]) indicated that a sample size of 17 subjects per group (n = 34) would be required to have 90% power at P = 0.05. A total of 20 subjects per group(n = 40) were recruited to allow for approximately 10% dropouts from the study sample." Reliability: "10 randomly selected baseline models of subjects were measured again after a 2‐week interval. There were mean differences between measurements of 0.07 mm in arch perimeter, 0.10 mm for the irregularity index, and 0.05 mm for the visual analog scale. The intra‐class correlation coefficients were 0.98, 1.00, and1.00, respectively, indicating excellent measurement agreement."
Participants	40 participants (20 in each group) with fixed orthodontic appliance 0.018 inch bracket slot system Inclusion criteria Children up to age 16 Fully erupted dentition from first molar forward Erupted or erupting second molars No missing or previously extracted permanent teeth Undergoing comprehensive orthodontic treatment with full fixed appliances Class II malocclusion requiring extraction of 2 maxillary premolars but no mandibular extractions
Interventions	From Miles 2016 article: "All patients were indirectly bonded with conventional 0.018‐in slot, MBT prescription brackets (Victory Series; 3M Unitek, Monrovia, Calif) on all mandibular teeth and the maxillary premolars and molars, whereas the maxillary incisors and canines were bonded with MBT equivalent prescription self‐ligating In‐Ovation C ceramic brackets (GAC International, Bohemia, NY)." Mandibular arch alignment (Miles 2016): "The archwires were identical in the 2 groups during the 10‐week experimental period: a 0.014‐in M5 Heaters thermal nickel‐titanium wire (G&H Wire, Franklin, Ind)." Maxillary arch space closure (Miles 2018): "The maxillary first or second premolars were extracted after the brackets were placed but before placement of the second 0.016x 0.022‐inM5 Heaters thermal nickel‐titanium wire (G&H Wire, Franklin, Ind). Approximately 10 weeks later, a 0.016 x 0.022‐in stainless steel wire with soldered posts (G&H Wire) was placed and allowed to align for 5 weeks, and an elastomeric chain was placed to consolidate the anterior 6 or 8 teeth. At the next visit, photos and alginate impressions of the maxillary arch were taken for the baseline data. In subjects having extractions of first premolars, the second premolar was tied with a stainless steel ligature that was left in place until the extraction space was closed. A 9‐mm nickel‐titanium medium Sentalloy coil spring (GAC International) was placed across the extraction sites from the bracket hook on the first molar, and the spring was activated between 6 and 9 mm and then ligated with a stainless steel ligature to the archwire hook mesial to the canine as per a previous study to deliver approximately 150 g, confirmed with a Dontrix gauge (E.T.M. Corporation, Monrovia, CA). Based on how much space remained to be closed, patients were recalled at 5‐ to 8‐week intervals to reactivate the coil spring. New alginate impressions were taken when the spaces on 1 side or both sides of the arch were almost but not fully closed; this was considered the end‐point for this study." Intervention Vibration forces to accelerate mandibular teeth alignment ‐ AcceleDent Aura appliance for 20 minutes per day Control No AcceleDent Aura appliance
Outcomes	Miles 2016 article Change in the mandibular arch perimeter ‐ measured from the distal contact of the mandibular canines and then to the labiolingual centres of each tooth (canine to canine) according to the unpublished study from the University of Texas Health Science Center at San Antonio Change in the LII for the mandibular arch ‐ LII measured at baseline, 5, 8 and 10 weeks Discomfort ‐ participant‐reported pain and discomfort VAS score at 5 time points (0, 6‐8 hours, 1 day, 3 days and 7 days) Miles 2018 article Rate of space closure in the maxillary arch Miles 2020 article Full duration of treatment
Notes	This study has 3 published articles reporting different outcomes.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	2‐arm block randomisation of 10 Page 930 "Randomization was performed using permuted blocks of 10 randomly generated numbers with the random generation function in Excel (Microsoft, Redmond, Wash)".
Allocation concealment (selection bias)	Low risk	The allocation numbers were sealed in opaque envelopes and shuffled by a staff member.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Study participants were not blinded to the intervention. Outcome measures included a patient‐focused questionnaire regarding pain and discomfort, scored on a VAS by participants.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded during assessment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Unclear risk	Study not registered and no protocol published
Other bias	Low risk	None

Nahas 2017.

Study characteristics
Methods	Study design: 2‐arm parallel RCT Setting: university teaching hospital in Dubai, United Arab Emirates Sample size calculation: not mentioned Reliability: measurement error was evaluated by re‐measuring the LII of 10 randomly selected casts on two occasions separated by a 2‐week interval. Both measurements performed by a single operator. A Dahlberg test for reliability revealed no significant differences between the measurements (P > 0.05).
Participants	40 participants due to receive fixed orthodontic appliance treatment were recruited Inclusion criteria: permanent dentition; requiring comprehensive orthodontic treatment, non‐extraction treatment plan, a LII of ≥ 2 mm and ≤ 10 mm score (lower anterior crowding); medically fit with good oral hygiene and healthy periodontium Exclusion criteria: active periodontal disease, taking any medication that might affect bone metabolism
Interventions	All study participants had the following. Self‐ligating bracket appliance (Empower; American Orthodontics, Inc.) with an MBT prescription and slot size of 0.022 × 028 inches Orthodontic treatment without teeth extraction 0.016‐in Heat Activated NiTi (HANT) initially placed and followed by a 0.018‐in NiTi until alignment of lower anterior teeth Recall every 2 weeks until good alignment of lower six anterior teeth was achieved Intervention group OrthoPulse LED device "...received OrthoPulse device (LED source) from Biolux® Ltd (Vancouver, Canada) and were instructed to use it daily for 20 min. The fitting procedures were performed by a single operator. The OrthoPulse device produced light at a wavelength of 850 nm and a power output of 90 mW/cm2. The estimated irradiation dose per session on the surface of the cheek was 108 J/cm2. Tracking software was integrated into the LED device to evaluate the compliance rate based on recordings of the numbers of sessions performed by each participant. A minimum compliance rate of 80% was required." Control group No OrthoPlus
Outcomes	Primary LII measured before and after alignment of the lower teeth. End of alignment defined as LII 0‐1 mm
Notes	Mandibular arch alignment only Non‐extraction Study duration: March to December 2012 Measurements for LII done on study models
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation ‐ participants asked to draw a sealed envelope that indicated their allocation to a test or control group (each with 20 participants) Paper page 131: "simple randomization by asking them to draw a sealed envelope (n = 40) that indicated their allocation to a test group (n = 20) in which LED photobiomodulation was delivered from an OrthoPulse device (Biolux® Ltd., Vancouver, Canada) or a control group (n = 20)"
Allocation concealment (selection bias)	Unclear risk	Paper stated that envelopes were sealed but did not mention if envelopes were opaque.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Clinicians and participants were not blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Single‐blinded investigator
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropouts: 2 from intervention group and 4 from control group. Intention‐to‐treat analysis was not applied.
Selective reporting (reporting bias)	Unclear risk	Study not registered and no protocol published
Other bias	Low risk	No concerns

NCT02868554.

Study characteristics
Methods	Study design: single‐blind parallel RCT,  3 arms Setting: University of North Carolina Orthodontics, Chapel Hill, NC, USA Sample size calculation: none mentioned
Participants	Up to 30 orthodontic patients of the University of North Carolina Orthodontic Residency Program People older than 18 years old, otherwise healthy, previously diagnosed with malocclusion "Inclusion criteria: Males or females over the age of 18 years old desiring orthodontic treatment. Adult dentition with all upper and lower front teeth present and any premolar and molar combination in the upper posterior of two teeth on each side. Normal pulp vitality and healthy periodontal tissues as determined by intraoral exam. Good health as determined by medical history. Willingness and ability to comply with study procedures, attend study visits, and complete the study. The ability to understand and sign a written informed consent form, which must be signed prior to initiation of study procedures. Exclusion criteria: Patient under the age of 18 years old Women may not be pregnant. Negative urine pregnancy tests prior to exposure to cone beam imaging is required to verify pregnancy status. Patients diagnosed with systemic diseases such as diabetes, hypertension (high blood pressure), temporomandibular disorders (jaw disorders), or craniofacial syndromes. Severe malocclusions that would require adjunctive procedures other than Invisalign. These include impacted teeth, closure of extractions spaces. Significant periodontal disease (> 4mm pocket depth or > 2 mm of recession on upper anterior teeth). Active caries not under care of either a dentist or periodontist. Chronic daily use of any non‐steroidal anti‐inflammatory medication, oestrogen, calcitonin, or corticosteroids. History of use or current use of any bisphosphonate medication or other medication for treatment of osteoporosis. Current smoker (must not have smoked in the last 6 months). Failing to comply with research protocols"
Interventions	3 groups  Experimental: accelerated Invisalign Participants receiving accelerated Invisalign therapy instructed to wear each aligner 24 hours day. Participants permitted to progress to the subsequent aligner after 4 days of compliant aligner wear. Experimental: accelerated Invisalign and vibration In addition to the accelerated Invisalign protocol as above, participants undergo intraoral vibration therapy using an AcceleDent Aura mouthpiece, which vibrates at 0.25 N (25 g) force level with a 30 Hz frequency, for 20 min per day. Control: standard Invisalign therapy Participants receiving standard Invisalign therapy instructed to wear each aligner 24 h per day. Participants permitted to progress to the subsequent aligner after 14 days of compliant aligner wear.
Outcomes	Primary LLI at baseline LLI at end of study, approx. 12 weeks Rate of OTM (difference in LII, mm/day at baseline and 12 weeks) Rate of OTM (total % change of LII at baseline and 12 weeks) Secondary Activity of bone turnover markers during orthodontic tooth movement (quantitative polymerase chain reaction, cycle threshold values (at 12 weeks)). Gingival crevicular fluid sampled to determine if vibratory stimulation during orthodontic tooth movement increases activity of the Receptor Activator of Nuclear Factor‐KappaB (RANK), Receptor Activator of Nuclear Factor‐KappaB Ligand (RANKL) and Osteoprotegerin (OPG) cell signalling pathway. Mean patient discomfort score (at week 12) Research participants asked to complete questionnaire at week 12. The FACES Pain Visual Analogue Pain Scale was used to assess pain on a 0 (no pain) to 10 (worst pain) grading scale.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"An independent, third party biostatistician, using an electronic program, R 3.4.2, completed randomisation of the subject allocation sequence. All subjects enrolled within the study were randomised in blocks of 6 to the 3 groups that correspond to one of the 3 treatment options to be studied."
Allocation concealment (selection bias)	Low risk	Allocation concealment was done by contacting the sequence generator for assignment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	No placebo or sham device
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	3 of the standard Invisalign group and 1 of the plus vibration group were lost to follow‐up. It does not seem intention‐to‐treat analysis was used.
Selective reporting (reporting bias)	Low risk	Peer reviewed article not published yet
Other bias	Low risk	None

Pavlin 2015.

Study characteristics
Methods	Study design: parallel RCT, 2 arms Setting: unknown Sample size calculation: "two‐sided alpha of 0.05, and 80% power, a sample size of 16 subjects per group (total of 32) was required to detect a statistically significant difference between the groups".
Participants	45 male and female participants Inclusion criteria Aged between 12 and 40 years Permanent dentition Participants had maxillary first premolars extracted as part of the orthodontic treatment Minimum of 3 mm of extraction space to be closed by distal movement of all 6 anterior teeth from canine to canine or by distal movement of the canines Good oral hygiene and compliance Exclusion criteria Any compromised medical or dental condition Participant currently involved in any other study, lives significantly outside San Antonio, or both Use of bisphosphonates Pregnant females
Interventions	"45 participants were bonded 0.022 x 0.028 in twin brackets (MBT, 3M Unitek, St. Paul, MN). After initial alignment, a mini‐implant was inserted and immediately loaded with 180g of force, which produced a predominantly translator canine movement, thus avoiding an unstable posterior dental anchorage that would compromise accurate measurements. To avoid excessive occlusal interferences, the bite was opened when necessary using composite build‐ups. Separate canine retraction was performed on 0.018 in stainless steel (SS) archwire and en masse retraction with a 0.019 x 0.025 SS archwire." Intervention group: OrthoAccel device provides a light vibration at 0.25 N and 30 Hz frequency for 20 min daily Control group: inactive sham device that was held in the mouth for 20 min daily
Outcomes	Primary Rate of orthodontic movement of a maxillary canine tooth being distalised to close an extraction space Secondary Adverse effects during treatment
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"A third‐party vendor provided a computer‐generated randomization schedule with a block size of 4 and stratified to ensure that the number of subjects aged 12–19 years and aged 20–40 years, as well as the number of subjects with “separate canine retraction” versus “en masse retraction” were equally distributed between the groups".
Allocation concealment (selection bias)	Unclear risk	No mention of allocation method
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participant blinding: intervention and sham device nearly identical Operator blinding: "both the investigators and the subjects remained blinded to treatment".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessor blinding: "Masking: Single Blind (Outcomes Assessor)" "The device was programmed to the assigned treatment by independent site personnel and both the investigators and the subjects remained blinded to treatment".
Incomplete outcome data (attrition bias) All outcomes	Low risk	9 out of 45 participants did not complete the trial. Intention‐to‐treat analysis was done. From the data, the authors state the number analysed as N = 45, with mention of the number of dropouts in each group.
Selective reporting (reporting bias)	High risk	We noticed that there was a disagreement in the reported outcome measures in the published article and results on ClinicalTrials.gov.
Other bias	High risk	The study was sponsored by OrthoAccel Technologies Inc, which is the manufacturer of the intervention appliance. The clinicaltrial.gov registration refers to a time‐limited agreement between the principal investigator and the sponsor to review results before release to public: "There is an agreement between Principal Investigators and the Sponsor that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo."

Reiss 2020.

Study characteristics
Methods	Study design: parallel RCT, 2 arms  Setting: university hospital  Sample size calculation: post hoc power calculation based on biomarkers ‐ 20 participants per group would allow detection of a 0.91 SD difference between groups using a 2‐sided 2‐sample t‐test with 80% power at the 5% significance level Reliability: one assessor. Two LII measurements for each cast were taken 1 week apart and averaged. Intraclass correlation coefficients calculated to assess reliability were above 0.85, which suggests good reliability.
Participants	40 participants (20 in each group) with fixed orthodontic appliance self‐ligating 0.022 inch bracket slot system Inclusion criteria: healthy, non‐smoker with no systemic medical conditions and taking no routine medications; 15 to 35 years of age at the time of bonding; non‐extraction treatment plan or no extractions required during the first 6 months of treatment; at least 5 mm of crowding in the mandibular arch; full‐complement dentition: first molar to first molar; good oral hygiene Exclusion criteria: requiring extractions as part of their treatment plan; smoking or excessive alcohol consumption; with edentulous areas (missing teeth); evidence of periodontal disease (any pocket depths > 4 mm); use of anti‐inflammatory drugs within 2 days of bonding; uncontrolled diabetes; dentofacial deformities (cleft palate, hemifacial microsomia, etc); routinely taking any of the following medications: corticosteroids (including for asthma), bisphosphonates, anti‐inflammatory drugs such as Ibuprofen, nicotine patch, oestrogen, opioids, growth hormone, relaxin, anti‐coagulants, stimulants (ADHD), diseases that could affect bone metabolism: parathyroid or thyroid dysfunction, osteoporosis or, osteomalacia, vitamin D deficiency, fibrous dysplasia, Paget’s disease, multiple myeloma, osteogenesis imperfecta, history of bone metastasis
Interventions	Intervention group AcceleDent device use, according to manufacturer's instructions, for 20 min a day throughout study Control group No AcceleDent device "Participants were bonded with Carriere passive self‐ligating brackets (Henry Schein, Melville, New York, USA), featuring a 0.022 Å~ 0.028‐inch slot. After the initial bonding appointment (T0), participants were scheduled for trial time points T1, T2, and T3 in conjunction with their regular orthodontic adjustments with their primary orthodontic provider every 4 to 6 weeks. At the bonding appointment (T0), a 0.014‐inch copper–nickel–titanium wire was engaged into the mandibular arch brackets and was re‐engaged at the T1 appointment. Before the 0.014‐inch copper–nickel–titanium wire was retied at the T1 appointment, it was removed from the participant’s mouth to verify that there was no permanent deformation that could confound the potential for lower incisor alignment. At T2, a 0.014 x 0.025‐inch copper–nickel–titanium wire was engaged. After data were collected at the T3 appointment, future wire size decisions were made by the primary orthodontic provider as the participant was no longer considered to be part of the trial."
Outcomes	Changes in expression of salivary biomarkers of bone remodelling. Saliva collected at T0 (baseline), T1 (5‐6 weeks), T2 (10‐12 weeks), T3 (15‐17 weeks). Saliva analysed for a variety of biomarkers (n = 17) with protein quantified by ELISA assay at each time point for each participant Alignment of mandibular anterior teeth. At each study visit, alginate impressions taken. These models analysed by 2 examiners to calculate the alignment based on LII, which measures the interproximal contact displacement in mm between the anterior teeth segment from the mesial canine on one side to the mesial aspect of the contralateral canine.
Notes	Results missing for other outcomes mentioned in the study register on ClinicalTrials.gov, e.g. orthodontic pain, oral health quality of life, tooth mobility
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation stratification according to sex and intervention "...randomization into the AcceleDent® or control group was performed separately for male and female subjects..."
Allocation concealment (selection bias)	Unclear risk	Participants were asked to select from 40 opaque envelopes with allocation group assignments inside; however, no description of allocation process safeguarding was mentioned.
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of study participants or clinicians
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Single assessor blinded to the study groups
Incomplete outcome data (attrition bias) All outcomes	Low risk	3 dropouts. Intention‐to‐treat analysis
Selective reporting (reporting bias)	High risk	Study registered on ClinicalTrials.gov, but some planned outcomes not reported including orthodontic pain, tooth mobility and oral health quality of life
Other bias	Unclear risk	Study registry stated that two investigators will assess the models, but in the published article, only one investigator was reported to have assessed the models. Post hoc sample size

Siriphan 2019.

Study characteristics
Methods	Study design: parallel RCT, 3 arms Setting: Orthodontic Clinic, Faculty of Dentistry, Prince of Songkla University Sample size calculation: "based on the results of a RCT that investigated the effects of three difference interventions on the rate of canine distalization (mean differences between methods = 0.35, 0.58 and 0.81 mm/month, difference in standard deviations = 0.34 mm/months, significance level = 0.05, power = 0.90). A minimum of 15 individuals/group was required. We recruited 20 subjects/group to compensate for dropout." The calculation was done using data from a study that did not use vibration forces. Reliability: measurements of 10 randomly selected records were repeated after a 4‐week interval. The level of significance was set at 0.05 for all analysis. Method error did not exceed 0.5 mm for linear variables and 0.5° for angular variables. Repeatability of measurement was acceptable (ICC = 0.86‐0.99).
Participants	60 male and female participants aged between 8 and 24 years Inclusion criteria Planning to have maxillary first premolar extraction followed by canine distalisation Good general health Good oral health, no signs of periodontal disease Exclusion criteria Excessive overbite History of immunosuppressive or bisphosphonate drugs ever History of anti‐inflammatory or steroid drug use within the 6 months before beginning treatment Unable to continue treatment or presented periodontal problems during the study
Interventions	Group 1: 30 Hz vibration Group 2: 60 Hz vibration Group 3: control "...each patient was fitted with fixed orthodontic appliance 0.022‐ inch slot Roth's prescription pre‐adjusted edgewise brackets (Roth system; Ormco Corporation, Orange, CA)...Arch wire 16x22 SS Force for canine distalization 60 cN force was used to distalize the maxillary canine using a NiTi closed‐coil spring that was calibrated and reactivated every 4 weeks. Only one canine (left or right) per subject was randomly selected for the study." "Vibratory devices were fabricated from electric toothbrushes...The magnitude of vibration was 0.1 cN; amplitude, 3.85 μm and acceleration, 9.81 m/s2...The average percentage coefficients of variation for the 30 and 60 Hz devices were 0.06 ± 0.01 and 0.03 ± 0.01, respectively." "From day 1 to day 7, all subjects were requested to attend the first investigator clinic daily. The maxillary archwire was removed, and the tip of the vibratory stimulus device was lightly placed at the mesial aspect of the cusp tip of the canine and switched on for 20 minutes. This procedure was also repeated for the subjects in the control group, except the device was not switched on. From day 8 to day 90, each subject was trained in self‐administration of vibratory stimulus and provided a vibratory device of the allocated frequency. A daily reminder message was sent to the subjects’ mobile phones. Subjects were requested to attend the first investigator clinic every 4 weeks for appliance activation and data collection."
Outcomes	Primary Space closure canine distalisation in mm/month; measured digitally on scanned models. Rates of canine and first molar movement were calculated as distance between cusp tips and between central pits, respectively, at T1 and T5 divided by treatment time Secondary RANKL and OPG secretion T1‐T5 Canine rotation was calculated as the angle between the mid‐sagittal line and a line passing through the mesio‐labio‐incisal point angle to disto‐labio‐incisal point angle of the canine on the digital study models. Angular changes between T1 and T5 were compared. Upper canines and molars tipping and angulation were measured using lateral cephalometric radiograph T1 and T5. T1: immediately before starting canine distalisation T2: 24 hours from the start of canine distalisation T3: 48 hours from the start of canine distalisation T4: 7 days from the start of canine distalisation T5: 3 months canine distalisation Intraclass correlation ranged from 0.993 to 0.995.
Notes	Only 3 months of canine distalisation No dropouts for the primary outcome but dropouts in the secondary outcome (8/60) RANKL and OPG with per‐protocol analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	3‐arm simple randomisation Page 132 "a randomization schedule was generated by a card shuffling method to randomly allocate the subjects into three groups".
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias) All outcomes	High risk	"The subjects and first investigator were not blinded to control/intervention group allocation. The subjects in the intervention groups were not aware of the frequency of vibration they were allocated to."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"All records collected were coded and shuffled to blind the co‐researcher who performed data measurements."
Incomplete outcome data (attrition bias) All outcomes	High risk	No dropouts for the primary outcome. Dropouts in the secondary outcome (8/60) RANKL and OPG with per‐protocol analysis.
Selective reporting (reporting bias)	Low risk	Study registered TCTR20170707004 in International Clinical Trial Registry Platform
Other bias	Low risk	No concerns

Taha 2020.

Study characteristics
Methods	Study design: single‐centre parallel RCT, 2 arms  Setting: university orthodontic clinic; Department of Orthodontics, School of Dental Medicine, University at Buffalo, NY Sample size calculation: calculated with reference to a prior study that reported a mean tooth movement per 28 days with conventional brackets over a 0.018‐in SS archwire as 1.17 ± 0.28 mm. To achieve power of 80%, with significance level 0.05, a minimum of 20 participants per group was required. Reliability: to assess intra‐ and inter‐examiner reliability, the same measurements on 10 participants (5 control, 5 experimental) were repeated at a 1‐week interval by the main investigator and by a technical specialist. Interclass correlation coefficients were calculated.
Participants	22 participants (11 in intervention group and 11 in control group) with fixed orthodontic appliance  0.022 inch MBT bracket slot system Inclusion criteria Healthy females and males between 12 and 17 years of age who were undergoing comprehensive orthodontic treatment on both arches Cases treated with unilateral or bilateral maxillary first‐premolar extraction; available canine retraction space of at least 3 mm Healthy teeth without any active caries or untreated lesions; healthy periodontal tissue (Modified Gingival Index grades 0 or 1); normal pulp vitality of the teeth undergoing retraction force Good ability to understand and sign the informed consent form Exclusion criteria Moderate‐to‐severe root resorption during orthodontic treatment Active periodontal disease Significant systemic condition, or used medications that may impact the study outcomes
Interventions	"Participants had comprehensive treatment by banding and bonding all teeth using 0.022‐in. slot edgewise (MBT) prescription. Once the provider prepared the case for maxillary unilateral or bilateral first‐premolar extraction (by levelling and aligning the teeth and/or by setting up anchorage methods), they referred the subjects to oral surgery for tooth extractions. Within 1–2 weeks after extraction, canine retraction mechanics were applied using 0.018‐in. stainless steel round wires (Ormco Corp., Orange, California). NiTi closed coil springs (Dentos Inc., Daegu, South Korea) were attached from the band hook on the first molar to the bracket hook on the canine and secured with a 0.010‐in. stainless steel single tie. The coil spring was activated to deliver 180 g of force measured by a Correx gauge (Haag‐Streit, Bern, Switzerland)". Intervention group  AcceleDent Aura (OrthoAccel Technologies, Bellaire, TX, USA) generates small vibrations at 30 Hz and 0.2 N Participants given direct instructions on operation and usage, being instructed to use their device for 20 min per day  at around 7 pm Control group  No vibrational appliance
Outcomes	Rate of maxillary canine retraction per month and amount of tooth displacement at each time point. All assessments and data collection were performed by the same investigator. Time points: assessed at 4‐week intervals. Follow‐up time points: T0 = day of NiTi coil‐spring delivery and initial canine retraction; first three‐dimensional (3D) intraoral scan; T1 = second intraoral scan, 4 weeks after T0; T2 = third intraoral scan, 8 weeks after T0; T3 = fourth intraoral scan, 12 weeks after T0. "The maxillary dental arch and the palate, including all rugae, were digitally scanned using an intraoral 3D scanner (i‐Tero Element II, Align Technology Inc., San Jose, California). Superimpositions and measurements of canine movement were conducted using OrthoAnalyzer software (3Shape Orthodontics System, Copenhagen, Denmark). For superimposition, three reference points were selected on the third palatal rugae on the T0 maxillary digital model and on each follow‐up scan magnified to 200%. The sequence of points’ selection started systematically from the upper left quadrant to the right one on each model. When the reference points were confirmed, the superimposition procedure was initiated using “dual view both sides on the same window” in the superimposition tool. Measurements were then made between the tips of the canine cusps on the superimposed models." Pain perception on day of activation, and every day at the same time for a period of 1 week using the VAS from 1 to 10. In the experimental group, participants were specifically asked to report level of perceived pain 1 h after using the device. Compliance data on device use were collected at each visit by downloading tracking information on the device.
Notes	Pain perception was assessed during canine retraction and not early in treatment.  Study not registered
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using a simple randomisation method, random table generation in GraphPad software (GraphPad, CA, USA) was carried out.
Allocation concealment (selection bias)	Unclear risk	No mention of the allocation process
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding for participants nor the clinicians
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding of assessor
Incomplete outcome data (attrition bias) All outcomes	High risk	1 from intervention group. No intention‐to‐treat analysis
Selective reporting (reporting bias)	High risk	Study not registered; no protocol published
Other bias	Low risk	None

Telatar 2020.

Study characteristics
Methods	Study design: parallel RCT Setting: Orthodonic Department of the Faculty of Dentistry at Akdeniz University, Turkey Sample size calculation: based on a prior study, which reported average monthly rate of tooth movement as 1.16 mm/month (95% CI 0.86 to 1.46) in the AcceleDent Aura group and 0.79 mm/month (95% CI 0.49 to 1.09) in the control group. Also, Miles 2018 suggested that a sample size of 7 participants per group would be required. Based on these data, G*Power package software was used to determine that at least 14 participants were required for control and case groups, with α = 0.05 type I error rate for 80% power in d = 1.70 impact width. Reliability: correlation between measurements described with Spearman correlation coefficient. Interclass correlation (ICC) was 95%, which represents excellent measurement agreement.
Participants	20 participants aged 13–18 years and whose treatment also included first premolar extraction (10 females, 10 males), 12 in intervention group and 8 in control group, with fixed orthodontic appliance  0.022‐inch MBT bracket slot system Inclusion criteria: individuals referred to the Orthodonic Department of the Faculty of Dentistry at Akdeniz University between March 2016 and November 2016 Exclusion criteria: no details
Interventions	"Each patient received MBT (technique according to McLaughlin, Bennett and Trevisi) preadjusted edgewise brackets (Mini Master Series, American Orthodontics, Sheboygan, WI, USA) with 0.022 inch slots on the canines and posterior teeth with a predetermined sequence of 0.014 inch, 0.016 inch, 0.018 inch, 0.016 x 0.022 inch, 0.017 x 0.025 inch, and 0.019 x 00.25 inch nickel–titanium (NiTi) wires inserted and ligated. After the initial alignment stage, a 0.019 x 0.025‐inch stainless steel wire was engaged passively to the buccal tubes and brackets and left in place for 1 month before commencing canine distalization. Miniscrews were used for direct anchorage and were inserted between first molars and second premolars. NiTi coil springs were used to apply 200  retraction force immediately. To avoid excessive occlusal interference, the bite was opened when necessary using composite build‐ups. The total study duration was 6 months and appointments were scheduled approximately every 4 weeks. The NiTi coil springs were reactivated at each appointment." Intervention group AcceleDent Aura (OrthoAccel Technologies, Bellaire, TX, USA) generates small vibrations at 30 Hz and 0.2 N. Direct verbal and written instructions given on operation and usage, instructed to use device for 20 min per day Control group No vibrational appliance
Outcomes	Rate of canine retraction (upper and lower) "All linear measurements were recorded digitally with the 3D Trios® System (3Shape Inc., Copenhagen, Denmark). Initial measurements were conducted after the levelling stage and prior to retraction of the canine tooth. Linear measurements were performed between mesial edges of molar tubes and distal edges of canine brackets."
Notes	Orthodontic mini‐screws were used for anchorage reinforcement. Trial registration NCT04206267
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Simple randomisation was achieved by coin tossing. This is not recommended in small sample studies.
Allocation concealment (selection bias)	Unclear risk	No mention of the allocation process
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding  "One investigator assigned the patients to study or control group and conducted the linear measurements with the 3D Trios® System, while another investigator treated the samples"
Blinding of outcome assessment (detection bias) All outcomes	High risk	"One investigator assigned the patients to study or control group and conducted the linear measurements"
Incomplete outcome data (attrition bias) All outcomes	High risk	No intention‐to‐treat analysis. Dropouts: 1 from intervention group
Selective reporting (reporting bias)	Low risk	Study registered at ClinicalTrials.gov (NCT04206267)
Other bias	Low risk	None

Woodhouse 2015.

Study characteristics
Methods	Study design: multi‐centre 3‐arm parallel RCT Setting: hospital: university teaching hospital King’s Dental Hospital, Brighton Hospital and William Harvey Hospital Sample size calculation: done for primary outcome alignment rate based on previous data relating to initial rate of orthodontic tooth movement using a Titanol aligning archwire (O'Brien 1990). Post hoc power calculations were done for the secondary outcome pain, OIIRR and space closure. Reliability: reproducibility of OIIRR measurements determined by repeated measurements of 20 sets of radiographs made 2 weeks apart from the same outcome assessor by calculating the intraclass correlation coefficient (range 0.998‐0.0976). For the study models LII measurements, 10 sets of baseline models were selected and remeasured after 2 wk. Analysis of variance with random effects showed high consistency in replications (F = 40.6; P < 0.0001). Intraclass correlation was 95% (CI, 91% to 99%). For space closure and PAR measurements, agreement of repeated measurements was excellent by the Bland‐Altman limits of agreement (mean difference 0.05 mm) and the concordance correlation coefficient (0.990). For pain, "each VAS score was measured on two separate occasions by the same operator; with the mean taken as the representative value".
Participants	81 participants Inclusion criteria Less than 20 years of age at start of treatment Medically fit and well In the permanent dentition Mandibular incisor irregularity Bilateral mandibular first premolar extractions as part of the treatment plan
Interventions	Bonding method and fixed appliance standardised between groups (MBT prescription pre‐coated 3M Victory series, 3M Unitek, Monrovia, USA) "After bracket bonding, a pre‐determined sequence of 0.014‐inch and 0.018‐inch nickel titanium archwires was used during the period of study. Archwire progression occurred only if full bracket engagement was achievable, which required the relevant archwire to be fully tied into the base of the bracket slot adjacent to each tie wing using elastomeric ligation".  "Space closure was initiated at the first visit after placement of a 0.019 x 0.025‐ in stainless steel working archwire and undertaken using 9‐mm nickel‐titanium coil springs attached from the first molar to hooks placed on the archwire between lateral incisor and canine, and stretched to no more than twice their length, as per the manufacturer's instructions". Data were collected at the start of mandibular space closure, first visit after initiation of space closure, end of space closure in the mandibular arch, and completion of treatment on removal of the fixed appliances. During the study, no bite planes, auxiliary arches, inter‐maxillary elastics, headgears or temporary anchorage devices were used. All participants were treated by consultant orthodontists or specialist registrars under their direct supervision. Interventions Group 1 Preadjusted edgewise fixed appliance treatment with 20 min daily use of an AcceleDent vibrational device (Accel group), a vibrational frequency of 30Hz and force of 0.2N to the dentition Group 2 Preadjusted edgewise fixed appliance treatment with daily use of a nonfunctional AcceleDent device (sham group) Group 3 Preadjusted edgewise fixed appliance treatment alone (fixed only group)
Outcomes	Primary Rate of tooth alignment in the mandibular arch using LII/day Secondary Number of visits Rate of mandibular space closure mm/month Severity of OIIRR in mm Patient perception of pain using VAS Duration of full treatment in months Peer Assessment Rating (PAR) score reduction
Notes	This study has four published articles reporting different outcomes.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation: computer‐generated randomisation sequence. No restricted randomisation or stratification was used. "The randomization sequence was generated by one investigator (MTC) using GraphPad online software with unrestricted equal participant allocation (1:1:1)"
Allocation concealment (selection bias)	Low risk	Participant allocation undertaken centrally at King's College London, independently from the clinical operators after recruitment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Clinicians were blinded as well as the study participants with the use of a sham appliance in one of the study groups.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessor blinded Page 4: "The pain questionnaires and extracted data were coded appropriately, so that both outcome assessor (NRW) and statistician (SNP) were blinded to subject allocation. The coding of the data was broken after the end of the analysis and no breach of blinding was identified."
Incomplete outcome data (attrition bias) All outcomes	Low risk	The dropouts were minimal in most outcomes other than space closure (n = 21), treatment duration (n = 20) and PAR score (n = 22). Although the analysis was done "per‐protocol", the authors reported that a separate sensitivity analysis was performed with the intention‐to‐treat sample, by including all excluded participants with available data, and compared with the main analysis for robustness, with no significant difference.
Selective reporting (reporting bias)	Unclear risk	According to the study registration NCT02314975, OIIRR was planned for mandibular incisors but published data was for maxillary central incisors. We contacted the author who responded that he is unsure why the study registration states that mandibular incisors will be assessed.
Other bias	Low risk	None

ADHD: attention deficit hyperactivity disorder; ANOVA: analysis of variance; AOB: anterior open bite; ASA: acetylsalicylic acid; CBCT: cone beam computerised tomography; CI: confidence interval; cm: centimetres; CT: computerised tomography; e.g.: for example; ELISA: enzyme‐linked immunosorbent assay;F: female; FMA: Frankfort‐mandibular plane angle; FPBB: fixed posterior bite block; g: grams; Gp: group; h: hour; HANT: heat activated nickel titanium; HIV: human immunodeficiency virus; Hz: hertz; ICC: intraclass correlation coefficient; in: inches; IPR: interproximal reduction; J/cm²: joules per square centimetre; LED: light emitting diode; LII: Little's Irregularity Index; LLL: low level laser; LLLI: low level laser irradiation; LLLT: low level laser therapy; LAIP: levelling and alignment improvement; M; male; min: minutes; MBT: McLaughlin‐Bennet‐Trevisi; MD: mean difference; mm: millimetres; MPR: midpalatal raphe; mW: megawatt; n: number; N: newtons; NiTi: nickel titanium; nm: nanometre; NRS: numerical rating scale; NSAIDs: non‐steroidal anti‐inflammatory drugs; OIIRR: orthodontically induced inflammatory root resorption; OLAT: overall levelling and alignment time; OPG: osteoprotegerin; OTM: orthodontic tooth movement; PFBB: posterior fixed bite blocks; PBM: photobiomodulation; PDT: photodynamic therapy; RANK: receptor activator of nuclear factor‐kappaB; RANKL: receptor activator of nuclear factor kappa‐B ligand; RCT: randomised controlled trial; sec: seconds; SD: standard deviation; SS: stainless steel; T: time point; TMJ: temporomandibular joint; VAS: visual analogue scale; v: version; W: watt; wk: weeks; 3D: three‐dimensional.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abd 2019	Systematic review
Abellan 2016	Split‐mouth study design
ACTRN12616000829415	Split‐mouth study design
ACTRN12619001237178	Split‐mouth study design
Al‐Jundi 2018	The laser therapy was used for an invasive procedure, which involved cutting tunnels in the attached gingiva.
AlShahrani 2019	Systematic review
Celebi 2019	Did not assess orthodontic tooth movement
Cronshaw 2019	Systematic review
CTRI201804013228	Split‐mouth study design. The intervention (laser) was applied as part of a split‐mouth RCT comparing self‐ligating brackets versus conventional brackets.
CTRI201804013520	Split‐mouth study design
Dalaie 2015	Split‐mouth study design
Elmotaleb 2019	Systematic review
Fernandes 2019	Not an RCT
Goymen 2020	Not an RCT
IRCT138804022066N1	Split‐mouth study design
IRCT2015030921406N1	Split‐mouth study design
IRCT2015100324324N1	Split‐mouth study design
Isola 2019	Split‐mouth study design
JPRN‐UMIN000013722	Split‐mouth study design ‐ mentioned cross‐over design. The authors were contacted to confirm but with no response.
Kansel 2014	Split‐mouth study design
Kau 2013	Not clear from the published article if the study was an RCT. The main author was contacted who confirmed that it was not.
Lo Giudice 2019	Did not assess orthodontic tooth movement
Lobre 2016	Did not assess orthodontic tooth movement
Lyu 2019	Systematic review
Matys 2020	Did not assess orthodontic tooth movement
Michelogiannakis 2019	Systematic review
Mistry 2020	Split‐mouth study design
NCT02181439	Split‐mouth study design
NCT02606331	Split‐mouth study design
Prasad 2019	Did not assess orthodontic tooth movement
Shipley 2019	Retrospective study
Yang 2019	Animal study
Yassaei 2019	Systematic review

Differences between protocol and review

The search strategy was revised and re‐run from scratch in September 2022; it was expanded to include more interventions (light‐emitting diodes, chewing gums and muscle training). 

There are no significant changes in the current review methodology compared to the methodology published in the protocol in 2013. However, the primary outcomes were described in more detail. We clarified that our SoF tables would report on pain as a patient‐centred outcome (rather than oral health related quality of life). 

Contributions of authors

Identifying relevant titles and abstracts from searches: Ahmed El‐Angbawi (AE), Grant T McIntyre (GM), David R Bearn (DB)
Obtaining copies of trials: AE, GM
Selection of trials: AE, PF, DB
Extracting data from trials: AE, GM
Entering data into RevMan: AE
Carrying out risk of bias assessment: AE, GM 
Carrying out analysis: AE
Interpreting the data: all review authors
Drafting the final review: all review authors 

Sources of support

Internal sources

• Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester; Manchester Academic Health Sciences Centre (MAHSC); and the NIHR Manchester Biomedical Research Centre, UK

  Support from Cochrane Oral Health at the University of Manchester 

External sources

• National Institute for Health Research (NIHR), UK

  This project was supported by the NIHR, via Cochrane Infrastructure funding to Cochrane Oral Health. The views and opinions expressed herein are those of the review authors and do not necessarily reflect those of the Evidence Synthesis Programme, the NIHR, the National Health Service, or the Department of Health and Social Care.

• Cochrane Oral Health Global Alliance, UK

  The production of Cochrane Oral Health reviews has been supported financially by our Global Alliance since 2011 (ohg.cochrane.org/partnerships-alliances). Contributors over recent years have been: British Association for the Study of Community Dentistry, UK; British Society of Paediatric Dentistry, UK; the Canadian Dental Hygienists Association, Canada; Centre for Dental Education and Research at All India Institute of Medical Sciences, India; National Center for Dental Hygiene Research & Practice, USA; New York University College of Dentistry, USA; NHS Education for Scotland, UK; Swiss Society for Endodontology, Switzerland.

Declarations of interest

There are no financial conflicts of interest; the review authors declare that they do not have any association with any parties who may have vested interests in the results of this review.

New search for studies and content updated (conclusions changed)