Correlation between temporomandibular disorders and the history of orthodontic treatment: A systematic review and meta-analysis

Abstract

Background:

This study aimed to investigate the correlation between the occurrence and development of temporomandibular disorders (TMDs) and the history of orthodontic treatment.

Methods:

Randomized controlled trials and non-randomized controlled studies investigating the correlation between the occurrence and development of TMDs and the history of orthodontic treatment were included in this study. A comprehensive search was conducted in the 5 databases of PubMed, Scopus, Web of Science, Embase, and The Cochrane Library to collect the literature published from the establishment of each database to March 2025. Meanwhile, other manual retrieval methods were also adopted to search for additional pertinent literature. The corresponding bias risk assessment tools were used to evaluate the quality of the included studies. Meta-analysis was performed for data combination to obtain the odds ratio of the correlation between the 2. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence of the outcome indicators.

Results:

5 studies finally met the inclusion criteria: 2 were prospective cohort studies, 2 were case-control studies, and 1 was a cross-sectional study. The total sample size comprised 6971 people, with 3165 males and 3806 females, respectively. The results of the Meta-analysis showed that there was no statistically significant correlation between TMDs and the history of orthodontic treatment (I² = 71%, odds ratio = 1.12, 95% confidence interval = 0.67 to 1.89, P = .66). The evaluation result of the certainty of evidence was of very low quality.

Conclusion:

Based on the current limited evidence, this study shows that there is no significant correlation between TMDs and the history of orthodontic treatment. Due to the limited certainty of the evidence, the interpretation of the result must be approached with caution. High-quality clinical studies are still needed in the future to supplement this research topic, so as to formulate high-level evidence-based clinical guidelines and optimize clinical decision-making and diagnosis and treatment services for patients. In order to prevent needless doctor-patient conflicts, orthodontists should closely monitor the potential risk of TMDs in patients with malocclusion in clinical practice.

1. Introduction

Temporomandibular disorders (TMDs) refers to a broad category of musculoskeletal conditions that include pain and/or dysfunction in the masticatory muscles, temporomandibular joint (TMJ), and related structures,^[1,2] with a global incidence of 34%.^[3] It often manifests as localized pain in the face and preauricular area, limited mandibular movement, and noise in the TMJ during mandibular movement.^[4] The etiology of TMDs involves a multifactorial interplay, with diverse contributing elements potentially participating in the pathogenesis.^[5] These factors encompass local mechanical, neuromuscular, neurobiological, biopsychosocial, and biomechanical domains,^[6,7] including but not limited to malocclusions, occlusal alterations, bruxism, tooth loss, anxiety, and depression.^[7-10]

The history of orthodontic treatment, as one of the local mechanical factors, has a controversial relationship with the onset and development of TMDs. The debate regarding the relationship between orthodontics and TMDs was already intense for several decades before 1992, but the 1987 Brimm versus Malloy Michigan lawsuit led to a significant increase in attention to this topic.^[11] Subsequently, the American Association of Orthodontists and more orthodontic scholars began to investigate occlusions, condylar positions, and various types of orthodontic treatments related to TMDs. These studies provided valuable information that significantly changed and advanced the orthodontic community’s understanding regarding TMDs.^[12] So far, most clinical studies^[6,13-15] and reviews^[16,17] have suggested that no evidence indicates that orthodontic treatment can cause or promote the occurrence and development of TMDs. Meanwhile, there is also no evidence showing that orthodontic treatment can improve or prevent the symptoms and signs of TMDs. In other words, there is no substantial connection between them. The research findings of Jeong et al^[18] showed that fixed orthodontic treatment does not significantly change the risk of adolescents developing TMDs. However, some studies^[19,20] and reviews^[21] suggest that a history of orthodontic treatment contributes to the development of TMDs and is a risk factor for TMDs. The results of the Meta-analysis by Coronel-Zubiate et al^[22] showed that the odds ratio (OR) of the correlation between the 2 was 1.84, with a 95% confidence interval (CI) of 1.19–2.83. They believed that there was a significant association between orthodontic treatment and the occurrence of TMDs. Other researchers, nevertheless, later questioned the reliability and validity of their results, claiming that the meta-analysis had issues with literature screening, data extraction, bias risk assessment, and statistical analysis.^[23]

Some new studies on this topic have recently been published.^[10,20,24] Therefore, updating the evidence-based medical evidence in this field is necessary to provide the latest and reliable basis for clinical decision-making for stomatological clinicians. This systematic review and Meta-analysis aim to investigate the association between the occurrence and development of TMDs and the history of orthodontic treatment and to answer the question: Is there really a correlation between TMDs and the history of orthodontic treatment?

2. Materials and methods

This study was designed and reported following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)^[25] and registered in PROSPERO, an international systematic review registry (ID: CRD420251012311).

2.1. Population, intervention/exposure, comparison, outcome, and study

The population, intervention/exposure, comparison, outcome, and study (PI/ECOS) framework is used in this study in the following ways:

1. P: Individuals with or without TMDs who agreed to participate.

2. I/E: Had either finished orthodontic treatment or had received it in the past at the time of the most recent examination and statistical analysis.

3. C: Had not been treated with orthodontics.

4. O: The OR of the correlation between TMDs and the history of orthodontic treatment.

5. S: Randomized controlled trials, controlled clinical trials, cohort studies, case-control studies, and cross-sectional studies.

2.2. Inclusion and exclusion criteria

Inclusion criteria: All studies that investigated the correlation between orthodontic treatment and TMDs. The necessary data could be extracted or incorporated from the studies. The diagnostic criteria for TMDs were unambiguous and must have included clinical examinations. The group with a history of orthodontic treatment history wasn’t significantly different from the group without treatment in terms of gender, or the gender factor had been adjusted. The subjects were 18 years old or older when they underwent the last clinical evaluation.

Exclusion criteria: Systematic reviews, dissertations, case reports, etc. The participants in the study were undergoing orthodontic treatment or had not completed it. Inability to extract or integrate reliable data. Duplicate published studies.

2.3. Search strategy

This study systematically searched 5 databases – PubMed, Scopus, Web of Science, Embase, and the Cochrane Library – using computers to collect literature published from the inception of each database up to March 2025. Searches were restricted to English-language publications. The search keywords encompassed “orthodontics,” “orthodontic,” “orthodontic treatment,” “malocclusion,” “temporomandibular joint,” “temporomandibular joint disorders,” “temporomandibular disorders,” “temporomandibular joint dysfunction,” “TMD,” “correlation,” “relationship,” “connection,” “link,” “prevalence,” “incidence,” and “frequency.” Subject headings and free words were combined using Boolean operators like “OR” and “AND” to link the search terms for retrieval. Refer to Table S1, Supplemental Digital Content 1 for detailed search strategies. Additional manual retrieval approaches were employed in this study besides searching the mentioned 5 databases to optimize the retrieval of pertinent literature and avoid bias brought on by incomplete inclusion of literature: We traced the references of relevant review articles and clinical studies associated with the topic. We conducted a manual review of the relevant research published in authoritative orthodontic journals, such as the American Journal of Orthodontics and Dentofacial Orthopedics, the European Journal of Orthodontics, the Angle Orthodontist, the Journal of Orthodontics, and the Korean Journal of Orthodontics.

2.4. Study selection

The EndNote X9 software (Thompson Reuters, Philadelphia) was utilized to manage all retrieved literature, and duplicate articles were subsequently excluded. Two researchers performed independent evaluations of the title and abstract. Following the removal of irrelevant literature, another researcher retrieved the full texts of the remaining studies and recorded the number of articles that were unavailable. Ultimately, 2 researchers thoroughly determined whether the literature fulfilled the eligibility criteria. Any disagreement in the study selection process had to be resolved through discussion among 3 individuals.

2.5. Data extraction

Before data extraction, all researchers extensively discussed and determined the items, variables, and data to be extracted from the included literature. The extracted content post-determination comprised the research author’s name, publication year, country, study design, number of subjects (male/female), mean age (range), number of patients in the orthodontic treatment group/untreated group, diagnostic criteria for TMDs, nature/methods of orthodontic treatment, data for meta-analysis, etc. The data extraction process was conducted independently by 2 researchers, while a third individual checked the extracted data. Any discrepancies were resolved through discussion.

2.6. Quality assessment of the included studies

Two researchers employed the appropriate evaluation tools for quality assessment based on the study design of the included literature. The ROB2 tool was employed to evaluate the risk of bias for randomized controlled trials.^[26] The ROBINS-I tool was utilized to evaluate the risk of bias for controlled clinical trials.^[27] For case-control studies and cohort studies, the checklists of the Newcastle–Ottawa Quality Assessment Scale (NOS), which were applicable to their own study designs, were used to assess the risk of bias.^[28] The tool consisted of 8 items with a total score of 9 points, including 3 groups: selection, comparability, and outcome/exposure. A modified NOS version of some research was used to assess the risk of bias in cross-sectional studies.^[29,30] It consisted of 6 brief items and 3 categories, totaling 7 points. Three researchers discussed and reached a consensus if there was disagreement during the risk of bias assessment.

2.7. Statistical analyses

The correlation between TMDs and orthodontic treatment history was evaluated employing the OR and 95% CI as effect analysis statistics. A meta-analysis was performed utilizing RevMan 5.4 software (Cochrane Group, UK). The heterogeneity between the outcomes of the included studies was judged by the Q Cochran tests and I² values. The fixed effect model was used for meta-analysis if the heterogeneity between studies was small (P > .1, I² ≤ 50%); if the heterogeneity was large (P ≤ .1, I² > 50%), the random effect model was used, and further subgroup analysis or sensitivity analysis was carried out to identify and address the source of heterogeneity. The test level for the meta-analysis was set at α = 0.05. If the number of included studies was insufficient, the outcome measurement standards were inconsistent, or the heterogeneity was too great to handle, the data were not merged, and only descriptive analysis was carried out. Publication bias was detected using Egger’s test, Begg’s rank correlation test, and funnel plot if the number of included studies for the meta-analysis was ≥10.

2.8. Certainty of the evidence

The evidence quality of outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The GRADEpro GDT online software (https://www.gradepro.org) was used to evaluate the quality grade of GRADE evidence and to create and generate the Summary of Findings table for certainty assessment.^[31,32] Four levels of evidence certainty could be identified for each outcome indicator based on the study design, risk of bias, inconsistency, indirectness, imprecision, and other considerations: high, moderate, low, or very low.^[33,34]

3. Results

3.1. Search results and study selection

A total of 6050 articles were obtained by retrieving 6047 from 5 databases and 3 from other sources. 3187 duplicate articles were intelligently removed after the article information was imported into the EndNote X9 software program. Following a review of the abstract and title, 29 articles that required full-text reading were selected, while 2837 articles that didn’t fulfill the inclusion criteria were eliminated. After obtaining the full text of 29 articles, 5 articles were eventually included after thorough reading and screening. The flowchart of literature screening^[25] is shown in Figure 1.

Figure 1.

The flow chart of literature screening.

3.2. Study characteristics

The basic characteristics of the included studies were elaborately described in Table 1. The 5 articles^{[6,15,24,35,36]} included in this study were from 5 different countries: the UK, Italy, Israel, Australia, and Korea. The included studies, which span from 2009 to 2024, contained 2 prospective cohort studies,^[6,35] 2 case-control studies,^[15,24] and 1 cross-sectional study.^[36] There were no randomized controlled trials or controlled clinical studies meeting the inclusion criteria. The included studies had sample sizes ranging from 174 to 5567, with 3 studies^[6,15,36] having sample sizes >300. In 3 of the 5 included studies, the mean age of the participants^[6,15,36] was beyond thirty. Although the orthodontic treatment group in 1 study^[36] had a lower mean age than the untreated group, the age factor was adjusted when calculating the OR. In the other 2 of the 5 included studies, the age range was 18 to 30 years in 1 study^[24] and 18 to 34 years in another study.^[35] In 3 studies,^[15,24,35] there was no gender difference between the TMDs group and the TMDs-free group, and all of the subjects in 1 study^[35] were female. One study^[6] showed that females were more likely to participate at the last follow-up but adjusted for gender when assessing the correlation between TMDs and orthodontic treatment history. In 1 study,^[36] the proportion of female subjects in the orthodontic treatment group (62.4%) was greater than that in the non-orthodontic treatment group (50.2%), but the gender factor was adjusted when calculating the OR. Among the included studies, 2 studies^[6,36] provided adjusted OR and 95% CI of the correlation between TMDs and orthodontic treatment history. One study^[6] not only adjusted for gender and school cluster but also adjusted for inclination score, while the other study^[36] adjusted for age, gender, educational differences, subjective mental stress, depression diagnosis, suicidal ideation, and income. The other 3 studies^[15,24,35] failed to provide the OR and 95% CI, and one of them^[35] provided the relative risk and 95% CI, but the OR and 95% CI were able to be generated from the data available in the original text. Of the 2 prospective studies, 1 had a follow-up period of 20 years, while the other experienced an average follow-up period of 30 months (8–42 months). Only 1 study^[15] reported the average time after the end of orthodontic treatment (14.3 ± 6.1 years), and all included studies didn’t mention the duration of orthodontic treatment.

Table 1.

The basic characteristics of the included studies.

First author	Year of publication	Country	Study design	Number of subjects (male/female)	Mean age or range	Number of patients in the orthodontic treatment group/untreated group	Diagnostic criteria for TMDs	Nature/methods of orthodontic treatment
Macfarlane	2009	United Kingdom	Prospective cohort study	337 (146/191)	30–31 yr	150/187	Modified dysfunction Helkimo index	Types of orthodontic appliances: removable appliances, fixed appliances, or removable and fixed appliances
Manfredini	2016	Italy	Case-control study	602 (147/455)	30–40 yr (TMDs group: 38.7 ± 6.6 yr; control group: 36.4 ± 8.6 yr)	213/389	RDC/TMD	Not mentioned
Shalish	2024	Israel	Case-control study	291 (131/160)	18–30 yr (TMDs group: 21.22 ± 4.01 yr; control group: 20.81 ± 1.49 yr. Orthodontic treatment group: 20.79 ± 2.71 yr; control group: 21.28 ± 3.75 yr)	119/172	Axis I of the RDC/TMD	Orthodontic treatment included: mandibular orthodontic treatment (102 subjects) and maxillary orthodontic treatment (113 subjects) of those 47 used a headgear. Type of orthodontic treatment: Fixed (102 subjects) and removable (21 subjects). Extractions during orthodontic treatment: 32 subjects. Retention after orthodontic treatment: removable (19 subjects), Fixed (52 subjects) and removable + fixed (27 subjects)
Slade	2008	Australia	Prospective cohort study	174 (0/174)	18–34 yr	99/75	RDC criteria	Not mentioned
Sim	2019	Korea	Cross-sectional Study	5567 (2741/2826)	The group with a history of orthodontic treatment: 31 ± 0.7 yr; the group without a history of orthodontic treatment: 46.6 ± 0.4 yr	258v/5309	The criteria of the World Health Organization	Not mentioned

RDC = Research Diagnostic Criteria, RDC/TMD = research diagnostic criteria for temporomandibular disorder, TMD = temporomandibular disorder.

3.3. The primary findings drawn from the included studies

This study included 6971 participants in total, 3165 of whom were male and 3806 of whom were female. It should be mentioned that the conclusions of the included studies were influenced by various confounding factors.

In the research performed by Macfarlane et al,^[6] the prevalence of TMDs in females exceeded that in males at other follow-up periods, with the exception of the baseline survey. Generally speaking, there is no correlation between orthodontic treatment and the onset or persistence of TMDs. For adults aged 30 to 31, the sole significant indicators of TMDs were female sex (OR = 2.99; 95% CI = 1.09–8.23) as well as having had TMDs during adolescence (OR = 4.47; 95% CI = 2.00–10.00). The study finally concluded that orthodontic treatment neither causes nor restricts TMDs. The sole predictors of TMDs in youth are female gender and a history of TMDs during adolescence.

The study by Slade et al^[35] demonstrated that during an average follow-up period of 30 months, individuals with a history of orthodontic treatment had a higher risk of TMDs compared to those without such a condition (relative risk = 3.03; 95% CI = 0.89–10.35). However, this finding wasn’t statistically noteworthy. It was believed that it was still too early to conclude that orthodontic treatment was a risk factor for TMDs, even if it was only in the subgroup of females carrying the pain-sensitive haplotype of catechol-O-methyltransferase. More research is needed to clarify the correlated effects of catechol-O-methyltransferase and orthodontic treatment in the development of TMDs.

The research performed by Shalish et al^[24] showed, through a multivariate analysis of patients with TMDs, that orthodontic treatment correlated with better oral hygiene (OR = 5.17; 95% CI = 1.04–25.59), a decreased amount of tender muscles (OR = 0.84; 95% CI = 0.74–0.96), and a lower (more favorable) Pittsburgh Sleep Quality Index score (OR = 0.86; 95% CI = 0.76–0.97). In the multivariate analysis of the complete study population, none of the examined parameters revealed a significant association with orthodontic treatment. Orthodontic treatment was considered irrelevant to the diagnosis of TMDs and its disease features.

The research conducted by Manfredini et al^[15] found that orthodontic treatment generally has no meaningful clinical impact on TMDs. The positive or negative medical history associated with ideal or nonideal orthodontic treatment has little relationship with different TMD diagnoses. They suggested that orthodontic treatment might not significantly influence TMDs.

Sim et al^[36] performed a study applying logistic regression analysis to assess the link between orthodontic treatment and TMDs. The findings indicated that, after correcting for age, gender, and psychosocial variables, the modified OR and 95% CI for orthodontic treatment and TMDs were 1.614 (1.189–2.190), 1.573 (1.162–2.129), and 1.612 (1.182–2.196), respectively. After controlling for confounding variables, the adjusted OR and 95% CI for orthodontic treatment and TMJ clicking were 1.778 (1.289–2.454), 1.742 (1.265–2.400), and 1.770 (1.280–2.449), respectively. They claimed that TMJ pain and functional disorders were unconnected to orthodontic treatment.

3.4. Quality assessment of the included studies

The quality assessment (risk of bias) of the included studies is presented in Table 2. One cohort study^[35] received 5 stars on the NOS, while another cohort study^[6] obtained 8 stars. The 2 case-control studies^[15,24] both had an 8-star NOS score. One cross-sectional study^[36] used a modified version of the NOS with a score of 6 stars. The main reasons for increasing the risk of bias are: the lack of “comparability,” “selection of the non-exposed cohort,” “outcome of interest not present at start” and “popularity of follow-up of cohorts” in cohort studies; the lack of “comparability” in case-control studies; the lack of “sample selection method” in cross-sectional studies.

Table 2.

Risk of bias assessment.

Cohort studies	Macfarlane et al	Slade et al	Case-control studies	Manfredini et al	Shalish et al	Cross-sectional studies	Sim et al
Selection			Selection			Selection
Representativeness of the exposed cohort	*	*	Is the case definition adequate	*	*	Representativeness of the study population	*
Selection of the nonexposed cohort		*	Representativeness of cases	*	*	Sample selection method
Ascertainment of exposure	*	*	Selection of controls	*	*	Ascertainment of exposure (risk factor) and outcome	*
Outcome of interest not present at start		**	Definition of controls	*	*
Comparability			Comparability			Comparability
Comparability of cohorts on the basis of the design or analysis	*	*	Comparability of cases and controls on the basis of the design or analysis	*	*	Adjustment for important factors	**
Outcome			Exposure			Outcome
Ascertainment of outcome	*	*	Ascertainment of exposure	*	*	Reliability of outcome assessment	*
Was follow-up long enough for the outcomes to occur	*	*	Method of ascertainment for cases and controls	*	*	Response rate	*
Adequacy of follow-up of cohorts		*	Nonresponse rate	*	*
Total scores	5	8		8	8		6
Quality	Medium	High		High	High		High

The NOS for cohort and case-control studies has a maximum score of 9. Studies scoring 7 to 9 are classified as high-quality, 4 to 6 as medium-quality, and <4 as low-quality. The adapted NOS for cross-sectional studies has a total score of 7. Studies scoring 5 to 7 are deemed high-quality, 3 to 4 medium-quality, and <3 low-quality. NOS = Newcastle–Ottawa Quality Assessment Scale.

^*1 score.

^**2 scores.

3.5. The results of the statistical analyses

This meta-analysis included 5 studies for the combined analysis of effect sizes to evaluate the association between TMDs and the history of orthodontic treatment. Due to the considerable heterogeneity among the studies (χ² = 13.62, I² = 71%), the random effects model was utilized to merge the outcome indicators. The overall effect reported in the forest plot (Fig. 2) showed that the OR was 1.12 (95% CI = 0.67–1.89, P = .66), suggesting that no statistically significant correlation exists between TMDs and orthodontic treatment history. The sensitivity analysis results indicated that the removal of the study by Shalish et al^[24] didn’t alter the direction of the results, while it presented a statistically significant correlation (OR = 1.48; 95% CI = 1.15–1.91; P = .002; Fig. S1, Supplemental Digital Content 2).

Figure 2.

Forest plot of the correlation between TMDs and the history of orthodontic treatment. CI = confidence interval, SE = standard error, TMD = temporomandibular disorders.

The subgroup analysis performed in accordance with the study design indicated (Fig. 3) that the “prospective cohort studies” subgroup displayed less heterogeneity (χ² = 0.07, I² = 0%), and the pooled effect size was 1.71 (95% CI = 0.55–5.30, P = .35). The subgroup of “case-control studies” showed increased heterogeneity (χ² = 5.12, I² = 80%), and the pooled effect size was 0.82 (95% CI = 0.38–1.75, P = .60). The pooled effect size for the subgroup of “cross-sectional studies” was 1.61 (95% CI = 1.18–2.20, P = .002). Since there was only 1 study within this subgroup, the reference value of the pooled effect size was limited. Therefore, more studies are still required in the future to enhance the meta-analysis on this topic. The detection of publication bias wasn’t performed due to the inclusion of fewer than 10 studies in the meta-analysis.

Figure 3.

Forest plot of the subgroup analysis of the correlation between TMDs and the history of orthodontic treatment. CI = confidence interval, SE = standard error, TMD = temporomandibular disorders.

3.6. Certainty of the evidence

The certainty of evidence regarding the correlation between TMDs and the history of orthodontic treatment was assessed using the GRADEpro GDT online software, and the result was a very low quality of evidence due to factors for downgrading the certainty of evidence in the domains of inconsistency and indirectness, as detailed in Table S2, Supplemental Digital Content 3.

4. Discussion

Numerous scientific studies^{[6,15,17,37-39]} to date have found that orthodontic treatment generally has no effect on TMJ and TMDs. These studies provide convincing evidence that orthodontic interventions fail to prevent or treat TMDs, nor do they substantially contribute to the development of TMJ-related issues. They are consistent with this study’s finding that no significant link exists between TMDs and orthodontic treatment history. Nevertheless, there have also been some studies recently that are contrary to the results of this study, suggesting that orthodontic treatment can affect the occurrence and development of TMDs.^[21,22] According to Alam et al’s^[21] meta-analysis of the 2 included studies, the combined effect size (OR = 1.59; 95% CI = 1.26–2.01; P < .0001) was significant, suggesting that orthodontic treatment may raise the risk of TMDs. Furthermore, the meta-analysis results of the 3 included studies (OR = 2.24; 95% CI = 1.79–2.82; P < .00001) indicated that patients with TMDs were more inclined to have orthodontic issues than patients without TMDs, demonstrating a significant correlation between patients’ TMDs and orthodontic problems. Only 1 study was included in a subgroup of their study, and the analysis results (OR = 0.68; 95% CI = 0.52–0.87; P = .003) indicated that orthodontic treatment was likely to have a negative effect on TMDs patients’ psychological well-being. The results may be affected by the following factors. First, there were few included studies. Only 3 relevant studies were included for the outcome indicator with the most included studies, and only 1 study was included for the 1 with the fewest. This decreased the credibility and reliability of the results. Additionally, the certainty of the evidence was not assessed. Second, there was controversy regarding the data used in the study for the synthesis analysis, and it was unclear where the data originated. Third, the study excluded literature prior to 2020, which artificially increased the risk of publication bias and affected the accuracy of the results.

Occlusion has long been considered one of the principal direct and/or indirect causes of TMDs.^[40] As a component of the TMJ system, it is a characteristic of TMDs patients.^[41] A more objective perspective on the connection between the 2 is that in certain situations, occlusal abnormalities may represent a key pathogenic factor.^[41] It is hard to avoid occlusal interference during orthodontic treatment, which may affect masticatory muscle activity and increase muscle discomfort in individuals with TMDs.^[42,43] In addition, occlusal interference brought on by the lateral displacement between the intercuspal and retruded contact positions can also lead to TMJ clicking. However, the signs and symptoms of TMDs in several patients reverted to normal after eliminating the occlusal interference. The study by Ding et al^[44] also showed that TMJ symptoms could arise while wearing functional appliances, but they would subside or go away throughout the course of the follow-up period. Therefore, in order to reduce the impact of occlusal interference and orthodontic devices on the emergence and development of TMDs during orthodontic treatment, and furthermore, to objectively evaluate the relationship between TMDs and orthodontic treatment, this meta-analysis only includes those studies that had completed orthodontic treatment.

There may also be some correlation between TMDs and particular kinds of malocclusions.^[5,45] A recent meta-analysis showed that the prevalence of TMDs was higher in patients with class II malocclusion, open bite, crossbite, and overjet.^[46] However, patients with malocclusion may seek orthodontic treatment.^[36] This could potentially result in those undergoing orthodontic treatment being more at risk for TMDs than non-treated patients. Only 1^[6] of the inclusion studies included in this meta-analysis recorded whether they had malocclusion at baseline. Although there were statistical variances at baseline, the study adjusted for these potential disparities by utilizing propensity scores. None of the other included studies took into consideration the potential impact of malocclusion factors on the research results. This might have instead biased the results in the opposite direction, increasing the likelihood that TMDs and a history of orthodontic treatment are clearly correlated. Nevertheless, the results of this study continue to show that there is no significant link between orthodontic treatment and TMDs. The credibility of the study’s results is indirectly enhanced by the confounding factor of malocclusion.

Some studies^[47-49] showed that before reaching adulthood, theoccurrence of TMJ clicking will increase with age. With the advancement of the adolescent puberty development stage, the prevalence of TMJ pain will also increase.^[18,50] This may be because the structure and function of TMJ are greatly impacted by the fast craniofacial growth that occurs during adolescence, leading to the frequent occurrence or fluctuation of the signs and symptoms of TMDs. In addition, the signs and symptoms of TMDs in children may be brief, in contrast to adults. Therefore, the inclusion of children and adolescents in the study population may lead to an increased number of false positives in the research results. This meta-analysis includes only relevant studies that evaluate adult subjects in order to reduce the impact of age factors.

At present, the majority of studies support the view that the prevalence of TMDs in females is higher than that in males.^{[3,6,45,46,51,52]} According to the findings of the meta-analysis conducted by Bueno et al,^[53] females are twice as likely as males to develop TMDs. This could be because women are more likely than men to suffer from depression and anxiety^[54] or because women are more vulnerable to estrogen fluctuations and endocrine dysfunction.^[3,46] Ribeiro-Dasilva et al^[55] suggested that in women with TMDs, the estrogen-induced hyperinflammatory phenotype may further worsen clinical pain through central sensitization. Considering the impact of gender on the results, this study excluded studies in which there were gender differences between the intervention group and the control group and the confounding factor of gender was not adjusted for.

Compared with previous evidence-based medicine research on related topics,^[18,21,22] this study had the benefit of having stricter eligibility criteria for the included literature, tightly controlled demographic characteristics like age and gender, and – most importantly – reasonably extracted and processed the data in the included studies, making the research results more reliable and persuasive. Simultaneously, this study extended the search strategy’s scope and incorporated more comprehensive and cutting-edge literature into the preliminary search phase. Although this increased our workload, it avoided search bias, which is another benefit of this study.

Although this study controlled for age and gender factors, the influencing factors of TMDs are multifaceted, and can also be impacted by potential confounding and mediating factors such as behavioral habits, psychological factors, genetic susceptibility, trauma history, and bruxism.^[18,24] In addition, the duration of orthodontic treatment, the quality of orthodontic treatment, the type of appliance, the follow-up time after the end of orthodontic treatment, and the diagnostic method of TMDs may also become potential confounding factors affecting the results of this study. Only 2 studies^[6,24] mentioned the type of appliance, only 1 study^[15] examined the follow-up time after the end of orthodontic treatment and the completion effect of orthodontic treatment, and no study mentioned the duration of orthodontic treatment. Furthermore, the TMDs diagnostic methods used in the literature were not entirely consistent. Therefore, high-quality prospective longitudinal studies utilizing the widely employed and standardized TMDs diagnostic method (such as research diagnostic criteria for temporomandibular disorders)^[56] were required in order to further investigate the impact of these factors on TMDs.

Caution must be exercised in interpreting the results of this study. According to the results of the sensitivity analysis, the findings of this study were unstable. Sensitivity analysis was performed on the remaining 4 studies after the study by Sim et al^[36] was omitted, and the findings were stable. This instability was caused by the poor quality of cross-sectional studies. The assessment of the certainty of GRADE evidence was of very low quality, suggesting that we have limited confidence in the observed values, and there may be considerable variation from the true values.^[57,58] Based on the findings of this study and a review of prior research,^[11,17,46] we advise that patients seeking orthodontic treatment be routinely examined and/or screened for TMDs at the initial visit, particularly for class II malocclusion and open bite patients. It is essential to manage TMDs pain before beginning orthodontic treatment. The dynamic monitoring of TMJ function should be reinforced during orthodontic treatment. When TMDs symptoms or signs appear, the present protocol of treatment should be discontinued immediately, and patient discomfort should be minimized as much as possible. After the symptoms are under control, orthodontic treatment can either be continued or tailored to the patient’s particular situation. Following these recommendations, orthodontists can lessen or avoid doctor-patient conflicts spurred on by TMDs issues in clinical settings.

4.1. Limitations

This study had the following limitations. First, the number of included studies was small, failing to detect publication bias. Second, three different study designs were included, and their varying quality and risk of bias – particularly among cross-sectional studies – increased the heterogeneity and instability of the results. Third, the diagnostic methods used for the TMDs included in the study weren’t precisely the same, resulting in classification bias and decreasing the consistency and comparability of the included study results. Fourth, although the eligibility criteria in this study had strict requirements for differences in demographic characteristics (age and sex), the influence of other confounding factors (such as malocclusion, follow-up time after the end of treatment) could not be excluded or avoided. Finally, the high heterogeneity (I² = 71%) suggests large differences in thefollowing aspects: different types of study designs among the included studies; inconsistent diagnostic criteria for TMDs; Different degrees of confounder adjustment: some studies adjusted for age, gender, and psychosocial factors, while others did not; Population and regional differences: the study participants were from different countries with diverse demographic and clinical backgrounds. High heterogeneity indicates that the pooled results should be interpreted with caution. Future meta-analysis studies should use higher eligibility criteria to increase the reliability and recognition of research findings.

5. Conclusions

This study indicates that there is no significant relationship between TMDs and orthodontic treatment history based on the small number of included studies and the review of numerous scientific studies. It should be emphasized that the certainty of evidence for the outcome indicators in this meta-analysis is very low, which does not support confident conclusions. Thus, the results should be interpreted with extreme caution. The impact of appliance type, orthodontic treatment duration, and posttreatment follow-up duration on TMDs should be the main focus of future studies. To reduce bias and enhance the quality of the study, it is advised that the study protocol design prioritize the use of standardized diagnostic methods and rigorously control confounding factors. To prevent unnecessary doctor-patient disputes, orthodontists should simultaneously be very aware of the potential risk of TMDs in patients with malocclusion and work toward early detection, early diagnosis, early communication, early control, and treatment.

Author contributions

Conceptualization: Xin Lang, Ge Guo, Zhengquan He.

Data curation: Xin Lang.

Formal analysis: Xin Lang, Ge Guo.

Methodology: Xin Lang, Ge Guo.

Resources: Xin Lang.

Supervision: Ge Guo, Zhengquan He.

Validation: Xin Lang.

Visualization: Xin Lang.

Writing – original draft: Xin Lang.

Writing – review & editing: Xin Lang, Zhengquan He.