Efficacy of advanced treatment modalities of dentin hypersensitivity: A systematic review and meta-analysis

Abstract

Background

Dentin hypersensitivity (DH) is a prevalent clinical condition characterized by short, sharp pain arising from exposed dentin in response to thermal, tactile, osmotic, or chemical stimuli. Conventional desensitizing agents often provide temporary relief, with inconsistent long-term effectiveness, prompting growing interest in advanced treatment modalities.

Objective

To systematically evaluate and compare the efficacy of advanced treatment modalities with conventional or placebo interventions in reducing dentin hypersensitivity in adults.

Methods

This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (Registration ID: CRD420250651753). Electronic searches were performed in PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar, with the date of final search being 30 September 2025. Randomized controlled trials involving adults with clinically diagnosed dentin hypersensitivity affecting permanent teeth were included. Advanced interventions such as laser therapy, photobiomodulation, bioactive glass, nano-hydroxyapatite, CPP-ACP, iontophoresis, Resin and varnish systems, were assessed. The primary outcome was reduction in hypersensitivity measured using validated pain assessment scales. Risk of bias was evaluated using the Cochrane RoB 2.0 tool, and quantitative synthesis was performed using a RevMan 5.4. software.

Results

Thirty-one randomized controlled trials were included in the qualitative synthesis, and twenty-five studies were eligible for meta-analysis. Advanced treatment modalities demonstrated a statistically significant reduction in dentin hypersensitivity compared with conventional or placebo controls (pooled SMD = −1.02; 95% CI: −1.32 to −0.73; p < 0.001). Laser-based therapies showed the greatest effectiveness, followed by nano-hydroxyapatite and bioactive glass agents. Moderate heterogeneity was observed across studies.

Conclusion

Advanced treatment modalities are more effective than conventional desensitizing agents in managing dentin hypersensitivity. Laser therapy provides the most consistent and sustained relief, supporting its clinical use, while further standardized long-term trials are recommended.

1. Introduction

Dentin hypersensitivity (DH) is a prevalent and clinically significant condition characterised by short, sharp pain arising from exposed dentinal surfaces in response to thermal, tactile, evaporative, osmotic, or chemical stimuli, pain that cannot be attributed to any other dental pathology.¹ Despite decades of research, DH continues to challenge dental practitioners, largely because its multifactorial aetiology intersects with variability in patient susceptibility, lifestyle behaviours, and clinical presentation. Global prevalence estimates range from 10% to 30%, with higher figures reported in populations with active periodontal disease, erosive dietary habits, or following periodontal surgical and non-surgical therapy.^2,3 This wide epidemiological burden underscores the urgency of identifying interventions that offer not only immediate symptom relief but also predictable, long-term benefit.

Conventional desensitizing agents including fluoride varnishes, potassium nitrate dentifrices, strontium salts, oxalate compounds, glutaraldehyde-based preparations, and early-generation dentin bonding systems have been employed routinely for decades. Their accessibility, ease of use, and cost-effectiveness make them practical first-line options for mild to moderate DH.^4,5 However, their long-term durability remains a recognised limitation: symptom relapse within weeks to months after application is commonly reported, and head-to-head comparisons with newer agents have generally not favoured traditional therapies over sustained follow-up periods.

In response to these limitations, advances in dental materials science and laser technology have introduced an expanding repertoire of treatment modalities. Bioactive glass (NovaMin), casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), arginine–calcium carbonate complexes, nano-hydroxyapatite (n-HAp), and advanced adhesive systems are increasingly investigated for their ability to promote remineralization, generate stable mineralised occluding layers within dentinal tubules, and produce sustained clinical relief.⁶ Laser-based therapies including diode, Nd:YAG, and Er,Cr:YSGG wavelengths have attracted considerable interest for their capacity to deliver immediate and durable desensitisation through neurological modulation and physical tubule obturation.^7,8

Despite the proliferation of available modalities, the clinical evidence base remains fragmented. Three interrelated challenges undermine the translation of existing research into evidence-based guidelines. First, DH is inherently multifactorial: aetiological contributors including gingival recession, erosive wear, toothbrush abrasion, periodontal therapy sequelae, and parafunctional habits vary considerably between individuals, limiting the generalisability of treatment effects across heterogeneous patient populations.⁹ Second, methodological inconsistencies — encompassing disparate pain measurement scales, inconsistent provocation stimuli, variable follow-up durations, and non-uniform reporting of outcomes — impede cross-study comparisons and evidence synthesis.¹⁰ Third, most clinical trials assess outcomes over short post-treatment intervals, whereas DH is inherently recurrent due to ongoing dentinal exposure from dietary acids, mechanical abrasion, and erosive processes. Long-duration comparative evidence is therefore critically needed.¹¹

There is a recognised scarcity of high-quality literature that clearly identifies the most effective and long-lasting treatment modality for DH. Traditional agents, while well established, often lack consistency in long-term outcomes. Conversely, modern agents and laser-based therapies show promising sustained efficacy but are frequently supported by smaller trials, limited follow-up periods, or non-standardised methodologies. This means that their true comparative effectiveness remains insufficiently understood.

Prior systematic reviews have tended to examine DH treatment in siloed categories potassium nitrate, fluorides, or laser therapy rather than providing a unified comparative synthesis across the full clinical spectrum.^12,13 Moreover, several newer modalities have entered the marketplace in advance of robust longitudinal validation: nanohydroxyapatite and bioglass formulations are widely marketed as superior options, yet long-term clinical data remain sparse. Similarly, laser therapy outcomes vary considerably across wavelengths, power settings, and study designs. These gaps collectively reinforce the need for a rigorously conducted, comprehensive systematic review.

Another challenge is that several newer treatment modalities have been commercialised rapidly, often ahead of robust clinical validation. For instance, nanohydroxyapatite toothpastes and bioglass-based formulations are widely marketed as superior options, yet their long-term clinical effectiveness remains under investigation.¹⁴ Similarly, laser-based treatments demonstrate considerable variability in outcomes depending on wavelength, power settings, technique, and study design, making it difficult to draw consistent conclusions.¹⁵ These inconsistencies reinforce the need for an updated systematic review that evaluates advanced modalities alongside established agents using rigorous methodological standards.

The present systematic review and meta-analysis was therefore designed to synthesise evidence from randomized controlled trials (RCTs) evaluating both traditional and advanced DH treatment modalities, with an explicit emphasis on short-term and long-term clinical outcomes. In doing so, this review seeks to bridge the gap between available evidence and everyday clinical decision-making, and to provide a structured, methodology-driven framework that supports the selection of the most effective and durable intervention strategies for dentin hypersensitivity.¹⁶

2. Methods

2.1. Study design

This systematic review and meta-analysis were methodically designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines and adhered to the methodological framework outlined in the Cochrane Handbook for Systematic Reviews of Interventions.¹⁷ The review protocol was prospectively registered in PROSPERO (Registration ID: CRD420250651753). The statistical analysis for this systematic review followed the Cochrane Handbook recommendations. Data from included randomized controlled trials were synthesized using both qualitative and quantitative approaches, depending on methodological homogeneity across studies.

2.2. Research rationale

Dentin hypersensitivity remains a clinically common condition for which conventional desensitizing agents offer inconsistent long-term relief. Advanced modalities including laser therapy and bioactive remineralising materials show clinical promise, but supporting evidence remains fragmented and not yet amenable to confident clinical recommendations. This systematic review and meta-analysis was therefore designed to critically compare advanced treatment modalities with conventional or placebo controls, with the objective of identifying interventions that offer effective and durable management of dentin hypersensitivity.

2.3. Research question

This systematic review was based on the following question: “What is the efficacy of advanced treatment modalities, compared with conventional or placebo treatments, in reducing dentin hypersensitivity in adults?”

The search strategy was prepared based on Population, Intervention, Comparison, and Outcome (PICO). Population (P) of interest were adults with clinically diagnosed dentin hypersensitivity affecting permanent teeth. The Intervention (I) included advanced modalities such as laser therapy, bioactive glass, nano-hydroxyapatite, CPP-ACP, iontophoresis, oxalate, arginine based, resin and varnish-based systems, and combination therapies. The comparison group (C) comprised of placebo, sham procedures, or conventional desensitizing agents. The outcome (O) focused on reduction in hypersensitivity measured using validated scales (VAS, Schiff Score), duration of symptom relief, and adverse effects. Only randomised controlled trials were included to ensure methodological rigor.

For the purpose of this review, “advanced treatment modalities” were defined a priori as interventions that employ enhanced biological, biomimetic, regenerative, energy-based, or delivery-assisted mechanisms beyond conventional desensitizing agents. These modalities were categorized into (1): Energy-based therapies (laser therapy and photobiomodulation); (2) Biomimetic and remineralising agents (nano-hydroxyapatite, CPP-ACP, and bioactive glass); (3) Delivery-enhanced systems (iontophoresis-assisted delivery); and (4) Advanced barrier-forming systems (resin- and varnish-based formulations designed to provide prolonged tubule occlusion). Conventional fluoride varnishes, potassium nitrate, and other traditional desensitizing agents were considered comparator interventions unless incorporated into modified delivery systems or combination therapies.

2.4. Inclusion criteria

• a.Randomized controlled trials (RCTs) only
• b.Adult participants (≥18 years) with clinically diagnosed dentin hypersensitivity
• c.Studies evaluating advanced desensitizing modalities, including laser therapy, bioactive glass, nano-hydroxyapatite, CPP-ACP, iontophoresis, oxalate, arginine based, resin and varnish-based systems and combination therapies
• d.Studies with a comparison group (placebo, sham, no treatment, or conventional desensitizing agents)
• e.Assessment of dentin hypersensitivity using validated pain scales (e.g., VAS, Schiff scale)
• f.Studies reporting quantitative outcome data with at least one month follow-up evaluation
• g.Full-text articles published in English

2.5. Exclusion criteria

• h.In vitro studies, animal studies, case reports, case series, reviews, editorials, or conference abstracts
• i.Studies involving children or adolescents or primary teeth
• j.Hypersensitivity secondary to caries, defective restorations, cracked teeth, pulpal involvement.
• k.Studies lacking standardized or validated outcome measures
• l.Studies with incomplete, unclear, or insufficient data for analysis

2.6. Literature search strategy

A comprehensive, systematic literature search was conducted across PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by Google Scholar for citation tracking, from database inception through 30 September 2025 (date of final search). The search was restricted to publications in the English language. Both MeSH terms and free-text keywords were combined using Boolean operators. A representative PubMed search string was: ("dentin hypersensitivity" OR "tooth hypersensitivity") AND ("laser therapy" OR "bioactive glass" OR "nano-hydroxyapatite" OR "CPP-ACP" OR "iontophoresis" OR "photobiomodulation") AND (randomized OR RCT). The Cochrane CENTRAL search was performed using key terms including “dentin hypersensitivity,” “dentine hypersensitivity,” and “randomized controlled trial,” without a structured Boolean string, given the nature of the CENTRAL interface. Reference lists of included studies and relevant systematic reviews were also manually screened to identify additional eligible trials. Grey literature and trial registries including ClinicalTrials.gov were also searched. All retrieved citations were imported into Zotero for deduplication, and the screening process was documented using a PRISMA 2020 flow diagram.

2.7. Study selection and data collection process

Prior to study selection and data extraction, reviewers independently screened and extracted data using standardized forms developed for this review. Disagreements were resolved through discussion and consensus, with arbitration by a third reviewer when necessary. Although the kappa value were not calculated, independent duplicate screening and extraction were performed throughout the review process to minimize selection and extraction bias. Reasons for exclusion at the full-text stage were documented systematically in accordance with PRISMA 2020 recommendations.

Data extraction was performed by the same two reviewers (VS and SS) using a standardised Microsoft Excel form. Extracted variables encompassed: study design and setting, participant demographics and diagnostic criteria, sample size, intervention and comparator characteristics, follow-up duration, outcome measures (mean VAS and Schiff score reductions with standard deviations), and details of adverse effects, funding sources, and conflicts of interest. When data were missing or ambiguous, corresponding authors were contacted to request clarification.

2.8. Risk of bias assessment

Methodological quality of included RCTs was independently evaluated by two reviewers (ST and PS) using the Cochrane Risk of Bias 1.0 (RoB 1.0) tool .The risk of bias was evaluated across seven domains: (1) random sequence generation (selection bias); (2) allocation concealment (selection bias); (3) blinding of participants and personnel (performance bias); (4) blinding of outcome assessment (detection bias); (5) incomplete outcome data (attrition bias); (6) selective reporting (reporting bias); and (7) other sources of bias. Each domain was judged as having a low, high, or unclear risk of bias. Any disagreements between the reviewers were resolved through discussion and consensus.

2.9. Statistical analysis and data synthesis

Meta-analysis was conducted using Review Manager (RevMan) version 5.4. Continuous outcomes were analysed using the standardised mean difference (SMD) with 95% confidence intervals. In anticipation of clinical and methodological heterogeneity across interventions, a random-effects model (DerSimonian–Laird method) was applied as the primary analytical approach. Statistical heterogeneity was quantified using the I² statistic; values exceeding 50% were considered indicative of substantial heterogeneity. Subgroup analyses were pre-specified based on the category of advanced desensitizing modality. Publication bias was assessed visually using funnel plots. Formal statistical tests for funnel plot asymmetry (e.g., Egger's regression test) were not performed, as several subgroups contained fewer than ten studies, which renders such tests underpowered and their results unreliable per Cochrane Handbook guidance.

Because hypersensitivity outcomes were reported using different measurement scales, including Visual Analogue Scales (VAS; 0–10 and 0–100) and Schiff Sensitivity Scores, standardized mean differences (SMDs) were used to permit quantitative synthesis across studies while preserving the relative magnitude of treatment effects.

3. Results

3.1. Study selection and characteristics of included studies

The systematic database search retrieved a total of 305 records from the primary databases, comprising PubMed/MEDLINE (n = 137) and Cochrane CENTRAL (n = 71). An additional 125 records were identified through other sources, including manual reference list screening, yielding an initial pool of 430 citations. Following deduplication (n = 53 removed), 377 unique records remained for title and abstract screening. Of these, 239 records were excluded on the basis of irrelevance or failure to meet the predefined inclusion criteria, leaving 138 articles for full-text assessment.

Full-text review resulted in the exclusion of 107 articles for the following documented reasons: intervention not meeting the inclusion criteria (n = 47); non-randomized or uncontrolled study design (n = 9); incomplete outcome data or unclear methodology (n = 27); inadequate follow-up duration (n = 16); and outcome measures not related to pain or dentin hypersensitivity reduction (n = 8). Ultimately, 31 studies met all eligibility criteria and were included in the qualitative synthesis; of these, 25 provided sufficient quantitative data for inclusion in the meta-analysis. The study selection process is illustrated in the PRISMA 2020 flow diagram (Fig. 1), and the characteristics of the included studies are presented in Table 1 ^{18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41} (seeFig. 2).

Fig. 1.

Prisma flowchart.

Table 1.

Characteristics of included studies.

Study (Author, Year)	Sample Size (n)	Control Group	Intervention Group	Assessment Method(s)	Outcome Measure(s)	Follow-up Duration
AlQahtani et al.18	75	2% NaF; 1.23% APF Gel	10% Propolis Hydrogel	Air Blast, Cold Water, Tactile	Schiff Score (0–4), VAS (0–10)	Baseline, Day 1, Day 14, Day 28
Arshad et al.19	128	NaF Toothpaste	FCPS, Pro-Argin, 8% Strontium Acetate	Air Blast, Tactile, Water	Schiff Score (0–4)	1 min, 3 Days, 2 Weeks, 4 Weeks, 6 Weeks
Barros et al.20	54	3% KNO3 Gel	PBM; PBM + 3% KNO3	Air Blast	VAS (0–10)	1 Week, 1 Month, 3 Months
Bahal et al.21	80	Pro-Argin	Oxalate Strip + Fluoride	Air Blast, Tactile	Schiff Score (0–4), VAS (0–100), Yeaple Probe	Baseline, 2 Weeks, 4 Weeks
Corral et al.22	31	Methacrylate Composite Resin	Silorane P90; Oxalic Acid Desensitizer	Air Blast, Tactile	VAS (0–100)	Baseline, 1 Months, 2 Months, 3 Months, 6Months, 1 Year
Das et al.23	45	Nano-Hydroxyapatite	Iontophoresis; Pro-Argin	Air Blast, Cold Water, Tactile	Schiff Score (0–4), VAS (0–10)	1 Day, 1 Week, 1Month, 3 Month, 6 Month
Ding et al.24	45	Calcium Carbonate Dentifrice	Nano-Carbonate Apatite Dentifrice	Air Blast	VAS (0–10), Schiff Score	Baseline, 2 Weeks, 4 Weeks
Guney et al.25	51	No Treatment	GaAlAs Laser; Er,Cr:YSGG Laser	Air Blast	VAS (0–10)	1 Week, 1 Month, 3 Months
Hatem et al.26	55	NaF Varnish	Gluma; Tetric N-Bond	Air Blast, Cold Water, Tactile	VAS (0–10), Schiff Score	Baseline, 1 Day, 2 Weeks, 1 Month
Hasan et al.27	48	Sham Laser; Saline	GaAlAs Diode Laser; NaF	Cold Air	VAS (0–10)	1 Week, 1 Months, 3 Months, 6 Months
Ivette et al.28	40	Placebo	CPP-ACPF; PBM	Air Blast, Tactile	VAS (0–10)	Baseline, Days 1–3, Month 1
Jalaluddin et al.29	30	NaF Varnish	Iontophoresis + APF Gel; Diode Laser	Tactile, Cold Air	VAS (0–10)	Baseline, 15 Day, 1 Month
Matsuura et al.30	40	Nanoseal	CAREDYNE Shield	Air Blast	VRS (0–4)	Baseline, 4 Weeks
Miron et al.31	7	ACP Gel	Nd:YAG Laser	Air Blast	VRS (0–4), LDF	Baseline, 1 Day, 7 Day, 1 Month
Narges et al.41	7	Sham Irradiation	660-nm Diode Laser; 810-nm Diode Laser	Dry Ice	VAS (0–10)	1–4 Weeks
Naghsh et al.32	20	Placebo	Diode Laser; Gluma	Air Blast, Cold Water	VAS (0–10)	Baseline, 15 min, 1 Weeks, 2 Weeks, 1 Months, 3 Months
Neuhaus et al.33	150	NUPRO Classic	NovaMin ± Fluoride	Air Blast, Tactile	Schiff Score, Yeaple Probe	28 Days
Patil et al.34	20	Gluma	Gluma Comfort Bond; Single Bond Universal	Air Blast, Cold Water, Tactile	VAS (0–10)	Baseline, 3 Weeks, 6 Weeks
Pepelassi et al.35	50	Fluoride-Free Paste	8% Arginine-Calcium Carbonate	Air Blast	Schiff Score (0–3), VAS (0–100)	Baseline, 2 Weeks, 4 Weeks, 6 Weeks
Seong et al.36	263	Fluoride Toothpaste	CSSP Toothpaste	Air Blast, Tactile	Schiff Score, VAS, Yeaple Probe	14 Days, 28 Days
Sharma et al.37	226	Sensodyne	Potassium Oxalate; LADD Mouthrinse	Tactile	VAS (0–10)	2 Weeks, 4 Weeks
Tevatia et al.38	120	Commercial Toothpaste	KNO3; GaAlAs Laser; Combination Therapy	Air Blast, Cold Water, Tactile	VAS (0–10)	2 Weeks, 4 Weeks, 6 Weeks
Vano et al.39	105	PrevDent	PrevDent Toothpaste; Colgate	Air Blast, Tactile	Schiff Score, VAS (0–10)	2 Weeks, 4 Weeks
Yilmaz et al.25	42	Sham Laser	Er,Cr:YSGG Laser	Air Blast	VAS (0–10)	Immediate, 1 Week, 1 Month, 3 Months
Young Lee et al.40	102	Strontium Chloride Dentifrice	n-CAP Dentifrice; Er,Cr:YSGG Laser	Air Blast, Tactile	Schiff Score (0–4), VAS (0–10)	1 Weeks, 2 Weeks, 4 Weeks

Abbreviations: APF = Acidulated Phosphate Fluoride; CPP-ACP = Casein Phosphopeptide–Amorphous Calcium Phosphate; CSSP = Calcium Silicate and Sodium Phosphate; FCPS = Fluorocalcium Phosphosilicate; KNO₃ = Potassium Nitrate; LDF = Laser Doppler Flowmetry; NaF = Sodium Fluoride; PBM = Photobiomodulation; VAS = Visual Analogue Scale; VRS = Verbal Rating Scale.

Fig. 2.

Risk of bias assessment.

3.2. Risk of bias assessment

The risk of bias assessment of the included randomized controlled trials was performed using the Cochrane Risk of Bias 1.0 tool, and the summary and graphical representation indicate an overall moderate methodological quality of the included studies.

3.2.1. Random sequence generation (Selection Bias)

Nearly all included studies demonstrated a low risk of bias for random sequence generation, indicating that appropriate randomization methods were commonly used. Only a small proportion of studies had some concerns in reporting regarding the randomization procedure, while no major high-risk concerns were identified.

3.2.2. Allocation concealment (Selection Bias)

Allocation concealment showed a comparatively lower proportion of low-risk studies than other domains. Although most studies adequately concealed allocation, a small percentage demonstrated high risk of bias, suggesting possible predictability in participant assignment. Some studies also lacked sufficient methodological details, contributing to some concerns judgments.

3.2.3. Blinding of participants and personnel (performance Bias)

This domain demonstrated one of the highest proportions of low-risk assessments. Most studies effectively blinded participants and study personnel, thereby minimizing the possibility of performance bias. Only a minimal proportion showed some concerns in reporting.

3.2.4. Blinding of outcome assessment (Detection Bias)

Blinding of outcome assessment revealed moderate concerns. While the majority of studies were categorized as low risk, a noticeable proportion showed high risk of bias, indicating that outcome assessors were not adequately blinded in certain studies. This may have influenced outcome evaluation and introduced detection bias.

3.2.5. Incomplete outcome data (Attrition Bias)

Most studies adequately addressed missing or incomplete data and maintained low attrition rates, resulting in a predominantly low risk of attrition bias. Very few studies showed some concerns, and high-risk attrition bias was uncommon.

3.2.6. Selective reporting (Reporting Bias)

Selective reporting bias was generally low across the included studies. Most studies reported outcomes consistent with their objectives and methodology, indicating transparency in reporting practices. No substantial high-risk reporting bias was observed.

3.2.7. Other Bias

The “other bias” domain also demonstrated predominantly low risk across studies. However, a moderate proportion of studies were judged as some concern due to insufficient methodological details or unidentified potential confounding factors.

3.2.8. Overall

The ROB summary graph suggests that the included studies were generally of good methodological quality, with most domains demonstrating predominantly low risk of bias. However, some concerns were observed in the domains of allocation concealment and blinding of outcome assessment, where a small proportion of studies exhibited high risk of bias. These methodological limitations should be considered when interpreting the overall findings of the review.

3.3. Meta-analysis: overall pooled effect

Meta-analysis of data from all 25 included trials demonstrated a statistically significant and clinically meaningful reduction in dentin hypersensitivity among participants receiving advanced treatment modalities compared with conventional or placebo controls. The pooled standardised mean difference was −1.02 (95% CI: −1.32 to −0.73; p < 0.001), representing a large effect size. Heterogeneity was substantial (I² = 91%), consistent with the diversity of interventions, patient populations, and follow-up protocols included, and confirming the appropriateness of the random-effects analytical model. The forest plot demonstrated a clear separation between intervention and control groups, with most individual study confidence intervals not crossing the line of no effect (Fig. 3). To explore potential sources of heterogeneity, subgroup analyses were conducted based on the type of advanced desensitizing modality used.

Fig. 3.

Forest plot with sub group analysis.

3.4. Subgroup analyses by modality

A formal test for subgroup differences demonstrated statistically significant variation in treatment effects across intervention categories (Chi² = 28.22, df = 7, P = 0.0002; I² = 75.2%). This finding suggests that the magnitude of desensitizing effect differed significantly among the evaluated treatment modalities and supports the subgroup analyses performed according to intervention type.

3.4.1. Iontophoresis based intervention

Two studies evaluating iontophoresis-based intervention yielded a pooled SMD of −1.25 (95% CI: −1.92 to −0.57), indicating moderate but statistically significant efficacy. These modalities consistently produced rapid initial desensitisation, often detectable within the first week of treatment. However, a degree of symptom recurrence was noted after 8–12 weeks in some trials, suggesting that iontophoresis may require periodic retreatment to sustain clinical benefit.

3.4.2. Laser-based modalities

A total of sixteen studies evaluated laser therapies, including diode, Nd:YAG, and Er,Cr:YSGG lasers, pooled together as a single subgroup. The pooled SMD was −2.11 (95% CI: −2.96 to −1.26; p < 0.001), demonstrating a strong and statistically significant reduction in hypersensitivity. Laser-based therapies consistently produced both immediate and sustained desensitisation up to 6 months. The high within-subgroup heterogeneity (I² = 93%) likely reflects variability in laser type, wavelength, power settings, and treatment protocols across included studies, and no further stratification by laser type was performed due to insufficient study numbers per device category.

3.4.3. Calcium phosphate-based agents

Three studies assessing calcium phosphate–based formulations (primarily CPP-ACP) demonstrated a moderate and statistically significant reduction in dentin hypersensitivity, with a pooled SMD of −0.72 (95% CI: −1.09 to −0.34). These agents exerted their effect through the release of bioavailable calcium and phosphate ions, facilitating remineralization and partial tubule occlusion at the dentinal surface.

3.4.4. Oxalate based agents

Three studies evaluating oxalate-based desensitisers produced a pooled SMD of −0.40 (95% CI: −0.92 to 0.12). The confidence interval crossed the line of no effect, and the reduction in hypersensitivity did not reach statistical significance. These results suggest that oxalate-based formulations do not offer a clinically meaningful advantage over control interventions in this body of evidence, although heterogeneity in product formulation and application protocols may have attenuated the detectable effect.

3.4.5. Arginine based formulation

Two trials investigating arginine–calcium carbonate formulations yielded consistent and statistically significant results, with a pooled SMD of −1.04 (95% CI: −1.37 to −0.72) and notably low heterogeneity (I² = 0%). This uniformity in effect across studies suggests a reliable and reproducible mechanism of action, likely attributable to the progressive occlusion of dentinal tubules through calcium precipitation facilitated by the arginine delivery system.

3.4.6. Bioactive glass-based agents

Two studies assessing bioactive glass formulations (e.g., NovaMin) demonstrated a significant, albeit variable, treatment effect (SMD = −1.08; 95% CI: −2.08 to −0.09). The relatively wide confidence interval reflects between-study variability in product concentration, particle size, application frequency, and follow-up duration. Nonetheless, the direction of effect was consistent and clinically meaningful, with these agents acting through ion-mediated hydroxycarbonate apatite crystallisation and stable dentinal tubule occlusion.

3.4.7. Nanoparticle-based desensitizing agents

Three studies evaluating primarily nano-hydroxyapatite (n-HAp) formulations demonstrated a statistically significant reduction in dentin hypersensitivity compared with controls, with a pooled SMD of −0.87 (95% CI: −1.50 to −0.25). The forest plot indicated moderate effectiveness with a consistent direction of effect favouring the intervention across all included trials.

3.4.8. Resin and varnish based system

Four studies investigated resin- and varnish-based desensitizing systems, yielding a pooled effect estimate of 0.50 (95% CI: −0.22 to 1.23). This confidence interval crossed the line of no effect, and the result favoured neither the intervention nor the control arm with statistical confidence. Resin and varnish systems therefore failed to demonstrate reliable efficacy in this meta-analysis, possibly reflecting the mechanical and durability limitations of film-forming agents under ongoing oral functional loading.

Formal statistical comparison between intervention subgroups was not undertaken because several categories contained a limited number of studies and exhibited substantial methodological and clinical heterogeneity. Consequently, subgroup findings should be interpreted as exploratory and descriptive rather than as evidence of statistically confirmed superiority of one modality over another.

3.5. Forest plot subgroup analysis

The forest plot presents a subgroup meta-analysis evaluating the efficacy of various advanced desensitizing treatments for dentin hypersensitivity. Subgroups include iontophoresis, laser therapy, calcium phosphate base, oxalate, arginine, bioactive glass, nanoparticle, and resin/varnish-based agents.

Across all studies (total sample 2721), the overall pooled effect favoured the experimental interventions over controls, with a standardized mean difference (SMD) of −1.02 [95% CI: −1.32, −0.73], indicating a clinically meaningful reduction in hypersensitivity scores. Heterogeneity was high (I² = 91%), reflecting the range of interventions and study populations (Fig. 3).

3.6. Publication bias

A funnel plot was constructed to assess publication bias. Visual inspection demonstrated a largely symmetrical distribution, suggesting an absence of substantial publication bias. Minor asymmetry observed likely reflects the inclusion of a few small-scale studies reporting positive findings. Formal statistical testing of funnel plot asymmetry using Egger's regression test was not performed, as the number of studies in several subgroups was below the minimum threshold of ten recommended for reliable application of such tests. This is acknowledged as a limitation of the present review (Fig. 4).

Fig. 4.

Funnel plot.

4. Discussion

This systematic review and meta-analysis synthesized evidence from 25 randomized controlled trials evaluating the efficacy of advanced desensitizing modalities for dentin hypersensitivity. The pooled results demonstrate a statistically significant and clinically meaningful overall reduction in sensitivity scores among participants receiving advanced treatments compared with conventional or placebo controls (SMD = −1.02; 95% CI: −1.32 to −0.73; p < 0.001). Subgroup analyses revealed considerable variation in treatment effectiveness across modality categories, a finding that reflects both mechanistic differences and disparities in the evidence base supporting each treatment class.

The significant subgroup interaction test (P = 0.0002) indicates that treatment effects varied according to intervention category. However, although laser-based therapies demonstrated the largest pooled effect size, these findings should be interpreted cautiously because substantial within-subgroup heterogeneity remained, particularly among laser studies (I² = 93%), reflecting differences in wavelength, power settings, treatment protocols, and follow-up periods.

4.1. Laser-based modalities

Laser therapies demonstrated the largest pooled effect sizes among the included interventions, producing the greatest magnitude of pain reduction across all subgroups (SMD = −2.11; 95% CI: −2.96 to −1.26; p < 0.001) however, these findings should be interpreted cautiously because of substantial heterogeneity and variations in laser parameters. All laser studies were pooled as a single subgroup; no further stratification by laser type was undertaken given the limited number of studies per device category. The substantial within-subgroup heterogeneity (I² = 93%) reflects genuine variability in laser type, wavelength, power settings, treatment protocols, and follow-up durations across included trials, and prevents definitive conclusions about the relative superiority of any particular laser system.^42,43

Mechanistically, laser-based therapies are proposed to reduce hypersensitivity through a combination of neurological modulation and physical tubule obturation. Low-level diode lasers (810–980 nm range) are thought to thermally modulate intradentinal neural activity and partially seal tubule apertures without inducing pulpal injury.⁴⁴ Higher-power ablative systems such as Nd:YAG and Er,Cr:YSGG lasers operate through different mechanisms including secondary dentin stimulation and surface modification, but their individual contributions could not be quantified in the present pooled analysis given the absence of device-stratified sub-analyses. Although complete operator and participant blinding is methodologically challenging in laser trials due to visible light emission and proprioceptive feedback, the consistency of pain reduction across included studies combined with a minimal adverse event profile (primarily transient mild warmth) supports the clinical reliability of laser therapy as a first-choice advanced modality, particularly for patients with moderate to severe DH refractory to conventional agents.

4.2. Nano-hydroxyapatite and bioactive glass-based agents

Biomimetic remineralising agents, specifically nano-hydroxyapatite (SMD = −0.87; 95% CI: −1.50 to −0.25) and bioactive glass (SMD = −1.08; 95% CI: −2.08 to −0.09), demonstrated the second-highest category of efficacy in this review. These agents act by releasing calcium and phosphate ions that precipitate as hydroxycarbonate apatite within and over dentinal tubule apertures, restoring mineral integrity at the dentin surface.^45,46

Meta-analyses show that n-HAp toothpastes significantly outperform controls for evaporative and tactile stimuli.²⁵ Previous studies have suggested that bioactive glass may provide longer-term tubule occlusion. However, heterogeneity in concentration (e.g., 5–15%), particle size, and application frequency limits direct comparability across trials. Long-term clinical data (6+ months) remain scarce, highlighting a need for standardized formulations.

4.3. Iontophoresis and CPP-ACP systems

Iontophoresis (SMD = −1.25 (95% CI: −1.92to −0.57), and casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) exhibited moderate efficacy (SMD = −0.72; 95% CI: −1.09 to −0.34). Iontophoresis enhances ionic diffusion (fluoride, calcium, phosphate) into dentin by means of low-intensity electrical current, resulting in deeper and more stable mineral deposition.⁴⁷

Recent randomized trials show significantly greater VAS score reduction when iontophoresis is combined with nano-hydroxyapatite or Pro-Argin pastes compared with topical use alone.²³ CPP-ACP acts by releasing bioavailable calcium and phosphate ions at the tooth surface, enhancing remineralization and promoting tubule occlusion.⁴⁸

Both treatments provide rapid relief within one week, though some relapse of symptoms may occur after 8–12 weeks. Variability in current strengths, application times, and small sample sizes suggest cautious interpretation.

4.4. Arginine-based formulations

Arginine–calcium carbonate formulations demonstrated consistent and reproducible efficacy across the two included trials, with a pooled SMD of −1.04 (95% CI: −1.37 to −0.72) and zero between-study heterogeneity (I² = 0%). This homogeneity is noteworthy and likely reflects the well-characterised, physico-chemical mechanism of arginine a positively charged amino acid that adsorbs to the negatively charged dentinal surface, facilitating localised calcium carbonate precipitation to form a stable crystalline plug within tubule lumina. The practical advantage of its incorporation into commercially available toothpaste formulations also enhances adherence and real-world generalisability.

4.5. Non-significant modalities: oxalate and resin/varnish systems

Oxalate-based agents (SMD = −0.40; 95% CI: −0.92 to 0.12) and resin/varnish-based systems (pooled estimate: 0.50; 95% CI: −0.22 to 1.23) did not demonstrate statistically significant efficacy in the present meta-analysis. For oxalate compounds, the formation of calcium oxalate crystals at the dentin surface is theoretically sound as a tubule-occlusive mechanism; however, the durability of these deposits under acidic oral conditions and masticatory loading has been questioned. In the case of resin- and varnish-based systems, mechanical degradation over time and limited depth of tubule penetration may undermine their ability to provide sustained relief. These findings should not necessarily be interpreted as evidence of complete therapeutic ineffectiveness; rather, they may reflect insufficient statistical power within available trials, combined with real limitations in occlusion durability.

4.6. Emerging and combination therapies

Emerging therapies such as ozone therapy, and propolis-based bioadhesives also reported clinically meaningful reductions in hypersensitivity.^49,50

Combination therapies particularly diode laser plus fluoride varnish or laser with nano-HAp produced superior improvements compared with single-modality interventions.⁵¹ These synergistic regimens may represent the future of multimodal DH management by combining rapid neural desensitisation with long-term remineralization. Future RCTs should formally evaluate such combination protocols with extended follow-up to determine their comparative long-term advantage.

Although platelet-rich fibrin (PRF) was initially considered during protocol development because of its proposed regenerative potential and emerging application in dentin hypersensitivity management, no studies satisfied the predefined eligibility criteria for inclusion in the present review. Consequently, no conclusions can be drawn regarding the effectiveness of PRF for dentin hypersensitivity. The absence of eligible evidence highlights a gap in the current literature and underscores the need for well-designed randomized controlled trials evaluating PRF using standardized outcome measures and adequate follow-up periods.

4.7. Quality of evidence and limitations

The risk of bias assessment indicated overall moderate methodological quality across the 25 included trials: 12 studies were rated as low risk, 9 as presenting some concerns, and 4 as high risk. Incomplete blinding particularly in laser-based trials was the most consistently identified source of potential bias, followed by inadequate allocation concealment and selective outcome reporting in a minority of studies. Funnel plot inspection did not reveal substantial publication bias, although minor asymmetry consistent with the selective publication of small positive trials cannot be entirely excluded.

Several limitations warrant acknowledgement. The high overall heterogeneity (I² = 91%) reflects genuine diversity in treatment protocols, populations, and follow-up periods rather than a methodological shortcoming, and is appropriately addressed by the random-effects model. The evidence base for several subgroups including iontophoresis, arginine, and bioactive glass remains limited to two or three trials, constraining the precision of pooled estimates. Additionally, the shortest mandated follow-up of one month may be insufficient to detect late relapse for some modalities, and the absence of standardised challenge stimuli across trials complicates direct outcome comparison.

Formal sensitivity analyses and meta-regression were considered but were not performed because several intervention subgroups contained only two to three eligible studies, which would have produced unstable and potentially misleading estimates. In addition, important study-level covariates including baseline hypersensitivity severity, stimulation methods, laser parameters, and follow-up schedules were inconsistently reported across studies. The substantial clinical heterogeneity among interventions with fundamentally different mechanisms of action further limited the interpretability of meta-regression outputs. Consequently, pooled findings should be interpreted cautiously, and the observed heterogeneity should be regarded as an important limitation of the present review.

Although statistically significant reductions in hypersensitivity were observed, interpretation of clinical relevance requires consideration of the minimal clinically important difference (MCID). Owing to variability in outcome measures and reporting methods across studies, a uniform MCID could not be established. Therefore, the present findings should be interpreted in terms of both statistical significance and the potential for clinically meaningful improvement as perceived by patients.

A formal GRADE assessment was not undertaken because the included evidence comprised highly heterogeneous interventions with substantially different mechanisms of action, outcome assessment methods, and follow-up periods. Several intervention categories were represented by only a small number of studies, and outcome reporting lacked sufficient uniformity to permit reliable certainty-of-evidence judgments across all comparisons. Application of the GRADE framework under these circumstances could have generated overly broad or potentially misleading certainty estimates. Nevertheless, methodological quality was systematically evaluated using the Cochrane RoB 2.0 tool, and study limitations were considered when interpreting the findings.

Follow-up durations varied considerably among included studies, ranging from immediate post-treatment assessments to six months or longer. The subgroup analysis according to follow-up duration (short-, medium-, and long-term) was not feasible because outcome reporting time points were inconsistent and several categories contained insufficient studies for meaningful pooled analysis. Consequently, conclusions regarding long-term effectiveness should be interpreted cautiously.

4.8. Clinical implications

The findings of this review provide a clear evidence-based rationale for the clinical adoption of advanced desensitizing modalities, particularly for patients who have not achieved adequate relief from conventional agents. Laser therapy and biomimetic calcium-based materials (nano-hydroxyapatite, bioactive glass, arginine) stand out as the most robustly supported options for sustained DH management. Clinicians should tailor treatment selection to individual patient profiles, accounting for symptom severity, prior treatment response, availability of equipment, patient preference, and cost considerations. A personalized, multimodal approach combining rapid neurological desensitisation with longer-term mineralising occlusion is likely to optimise clinical outcomes and patient satisfaction.

4.9. Future directions

Future research should focus on well-designed, large-scale randomized controlled trials with standardized intervention protocols and longer follow-up periods to assess the durability of treatment outcomes. Direct head-to-head comparisons between advanced desensitizing modalities are needed to establish relative effectiveness. Future studies should incorporate uniform pain assessment methods, patient-reported outcome measures, and cost-effectiveness analyses. Investigating combination therapies and emerging biomimetic materials may provide insights into achieving both immediate and long-term relief from dentin hypersensitivity.

5. Conclusion

This systematic review and meta-analysis provide comprehensive, high-level evidence that advanced treatment modalities may provide greater efficacy in reducing dentin hypersensitivity than conventional or placebo comparators. Among evaluated interventions laser therapy appeared to demonstrate larger pooled effect sizes whereas biomimetic agents including nano-hydroxyapatite, bioactive glass, and arginine-calcium carbonate showed promising and clinically meaningful benefits. However, considerable heterogeneity, variations in treatment protocols, and limited long-term follow-up warrant cautious interpretation of these findings. Iontophoresis and CPP-ACP offered moderate efficacy, whereas resin- and varnish-based systems and oxalate formulations did not achieve statistically significant superiority over controls in the available evidence.

The consistency of benefit observed across trials of moderate-to-high methodological quality supports the clinical integration of advanced modalities as a component of evidence-based DH management. However, high overall heterogeneity, limited long-term follow-up in several subgroups, and variable intervention protocols underscore the continued need for large-scale, standardised RCTs. In clinical practice, a personalized multimodal approach combining therapies with complementary mechanisms of action is most likely to deliver optimal and sustained long-term outcomes for patients with dentin hypersensitivity.

Ethical statement

This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (Registration ID: CRD420250651753).

Human and animal statement

We are uploading herewith the manuscript “Efficacy of Advanced Treatment Modalities of Dentin Hypersensitivity: A Systematic Review And Meta-Analysis”, for the publication as a review article in your esteemed journal ‘Journal of Oral Biology & Craniofacial Research”.

We assure you that no human or animal has been directly involved in this study as it is a systematic review article.

Source of funding

The authors declare that no financial support, grants, or other funding were received from any public, commercial, or not-for-profit organization for this study.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.