Abstract
Notes
Authors’ Contributions
P.A. participated in data collection and writing the manuscript. B.B., S.B.B., and K.A. participated in the study design and performed the statistical analysis. K.B. and R.D. participated in the study design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
References
Fig. 1
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Table 1
| Outcome | Certainty assessment | No. of patients | Effect | Certainty | Importance | ||||||||||
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| No. of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Experimental | Control | Relative effect (95% CI) | Absolute effect (95% CI) | |||||
| TMD incidence after third molar extraction (cohorts) | 2 | Non-randomised cohort studies (Huang and Rue19 [2006], Huang et al.18 [2008]) | Serious (registry-based outcome misclassification) | Not serious | Not serious | Not serious | None | 17,419 extracted (391 TMD cases; 2,217 extracted) | 17,072 unextracted; 2,217 matched controls | RR 1.6 (95% CI 1.3-2.0), RR 1.4 (95% CI 0.9-2.2) | ~3%-6% higher absolute risk in extraction group | ⨁◯◯◯ Very low | Critical | ||
| TMD prevalence in those with vs. without prior 3M removal (cross-sectional) | 1 | Cross-sectional survey (Barbosa et al.20 [2016]) | Serious (self-report of extractions; possible recall bias) | Not serious | Not serious | Serious (wide CI, limited generalizability) | None | 1,381 (with or without extraction history) | 1,381 (internal comparator) | OR 1.30 (P=0.041), OR up to 2.15 in subgroups | Not estimable in absolute terms | ⨁◯◯◯ Very low | Important | ||
| Symptom reduction with extraction+regimen vs. regimen only (RCT) | 1 | Randomised trial (Gururaj et al.16 [2023]) | Not serious | Not serious | Not serious | Not serious | None | 215 extraction group | 215 non-extraction group | RR 1.84 (95% CI 1.46-2.31) | 96% reduction in TMD symptoms with extraction | ⨁⨁⨁⨁ High | Critical | ||
| Incident TMD after mandibular 3M surgery (prospective cohort) | 1 | Prospective cohort (Munawar et al.17 [2016]) | Not serious | Not serious | Not serious | Very serious (small sample, wide CI) | None | 22 surgery patients | 20 control | RR 5.0 (95% CI 1.26-19.87) | 2 new TMD cases in extraction group at 6 months | ⨁◯◯◯ Very low | Critical | ||
| Postoperative preauricular/masticatory pain symptoms after 3M surgery (RCT) | 1 | Randomised controlled trial (Uppgaard et al.23 [2024]) | Low risk (validated measures, good retention) | Not serious | Not serious | Serious (OR 3.44, 95% CI 1.49-7.92, but subgroup only) | Device COI noted | 86 device; 83 manual support | Internal comparators | No difference between groups (P≥0.46); predictors: fully impacted molars OR 3.44 (P=0.004) | ~30%-35% prevalence across both groups | ⨁⨁⨁◯ Moderate | Important | ||
| Systematic review evidence | 1 | Systematic review (Damasceno et al.22 [2020]; 7 non-RCTs) | Serious (QUIPS: 4 moderate, 3 high RoB) | Not serious | Not serious | Serious (heterogeneity; imprecision) | Publication bias possible | Pooled across 7 studies | Mixed | OR 1.81-2.15; RR ~2.1 | Consistently higher TMD after extraction | ⨁◯◯◯ Very low-low | Critical | ||
Table 2
| Study | Country | Study design | Sample size (n) and demographic | Population | Intervention (extraction) | Comparator | Follow-up |
|---|---|---|---|---|---|---|---|
| DeAngelis et al.21 (2009) | Australia | Cross-sectional clinical assessment | 60 patients referred for third molar removal (age/sex not detailed) | Consecutive referrals to a hospital OMFS unit | Not an interventional study; preoperative assessment of patients referred for third molar extraction | None | Baseline only |
| Barbosa et al.20 (2016) | Portugal | Cross-sectional university survey | 1,381 (mean age 21.7±3.9 years; 75.5% female) | University students (Oporto district) | Self-reported history of TMR | No TMR | None (cross-sectional) |
| Huang et al.18 (2008) | USA | Population-based matched cohort | 2,217 with third molar extraction matched to 2,217 without; ~50% aged 10-20 years; 36% female overall | HMO enrollees (Kaiser Permanente Northwest) | Third molar extraction (severity, arch, anesthesia recorded) | No lifetime third molar removal (radiographically verified) | Up to 6 years (1998-2003); person-years accrued |
| Huang and Rue19 (2006) | USA | Retrospective cohort with time-varying exposure | 34,491 (continuous 5-year coverage from age 15 years); 17,419 had extractions; 391 TMD cases; 73% female among TMD | Statewide dental-insurance enrollees (Washington, D.C.) | Third molar extraction (arch, anesthesia, provider, difficulty) | Non-extracted time served as comparator (same cohort) | Minimum 5 years |
| Gururaj et al.16 (2023) | India | Randomized controlled trial | 430 (215 study, 215 control); mean age ~38 years; ~60% female | TMD patients with supraerupted/distoverted maxillary third molars | Multiphase therapy including extraction of supraerupted/distoverted third molars (study group) | Multiphase therapy without extraction (control) | 9 months |
| Munawar et al.17 (2016) | Malaysia | Prospective cohort study | 42 (22 operative; 20 control); mean age 23-24 years; both sexes | Patients indicated for mandibular third molar surgery | Third molar surgery (operative group) | No surgery (control group) | 6 months (baseline, 1 week, 1 month, 3 months, 6 months) |
| Uppgaard et al.23 (2024) | USA/Canada (multi-site) | Single-blind randomized controlled trial | 169 (86 device; 83 manual support); mean age 20.8 years; 65% female, mostly Caucasian | Healthy young adults undergoing third molar surgery with sedation | Extraction with Restful Jaw device for mandibular support | Extraction with manual support by dental assistant | 6 months (1, 3, 6 months assessments) |
| Damasceno et al.22 (2020) | Brazil/Nicaragua | Systematic review (PROSPERO registered, CRD42019065949) | 7 included clinical studies; total sample across studies varied (hundreds to thousands) | Adolescents and adults undergoing third molar extraction | Third molar extraction | Non-extraction groups (when available) | Variable (3 months to 6 years across included studies) |
Table 3
| Study | Extraction type | Comparator | Primary outcome | Effect estimate (if reported) | P-value | Clinical interpretation |
|---|---|---|---|---|---|---|
| DeAngelis et al.21 (2009) | Third molar extraction (referral population) | No comparator group (cross-sectional assessment) | Prevalence of TMD signs/symptoms in patients referred for extraction | 13.3% TMD-only; 23.3% mixed TMD+third molar symptoms | Not reported | TMJ/TMD signs common (36.6%) in extraction referrals; highlights diagnostic overlap and risk of overlooking TMD. |
| Barbosa et al.20 (2016) | Third molar removal (self-reported history in university students) | No removal | TMD diagnosis by RDC/TMD; associations with TMR | OR=1.30 (95% CI not given); also OR=1.69 for TMD Groups I+III; OR=2.15 for Groups I+II+III | 0.041 (overall); 0.045-0.006 (combined groups) | TMR independently associated with increased TMD prevalence; risk stronger in combined diagnoses. |
| Huang et al.18 (2008) | Third molar extraction (population-based cohort; 2,217 pairs) | Age- and gender-matched unextracted controls | Incidence of TMD (per ICD codes) | RR=1.4 (95% CI 0.9-2.2); under 21 years: RR=1.6 (95% CI 0.8-3.1) | >0.05 (NS) | Slight, non-significant increase in TMD risk overall; higher in <21 years and during first year after extraction. |
| Huang and Rue19 (2006) | Third molar extraction (insurance claims; 34,491 subjects) | Unextracted time within same cohort | Risk of TMD diagnosis (insurance claims) | Adjusted RR=1.6 (95% CI 1.3-2.0); ~23% of TMD cases attributable to extraction | <0.05 (significant) | Stronger evidence that extraction is a risk factor for TMD, with population-attributable risk of 23%. |
| Gururaj et al.16 (2023) | Extraction of supraerupted/distoverted maxillary third molars as part of a multiphase TMD regimen | Same regimen without extraction | Reduction in TMD symptoms (VAS pain, clicking, headache, neck pain) at 3, 6, 9 months | 96% reduction in TMD symptoms in extraction arm vs. control | <0.05 | Therapeutic extraction of supraerupted/distoverted maxillary third molars substantially improves TMD symptoms when added to standard care. |
| Munawar et al.17 (2016) | Mandibular third molar surgery (operative group) | No surgery (control) | Incidence of TMD signs/symptoms by DC/TMD across 6 months | Early post-operative spikes: trismus 92%, myofascial pain 69%, clicking 77% at 1 week; 2 new TMD cases at 6 months; operative >control | <0.005 | Third molar surgery associated with higher short-term TMD signs/symptoms vs. non-operative controls; some symptoms persist to 6 months. |
| Uppgaard et al.23 (2024) | Third molar removal with Restful Jaw device mandibular support | Third molar removal with manual mandibular support | Occurrence of post-operative PMMPS at 1, 3, 6 months | No difference between device vs. manual at any time; pain occurrence ~35% (1 month), 24% (3 months), 23% (6 months); fully impacted molars predict pain: OR 3.44 (95% CI 1.49-7.92) | Group comparisons ≥0.46; predictor 0.004 | Support method doesn’t change PMMPS risk; impaction status is a significant predictor of post-operative pain. |
| Damasceno et al.22 (2020) | Third molar extraction (systematic review of 7 clinical studies) | No extraction cohorts where available | TMD signs/symptoms following extraction | OR 1.81-2.15; RR ≈ 2.1; 6/7 studies showed increased TMD after extraction; certainty low-moderate | (Varies by study; generally significant in 6/7) | Evidence suggests third molar extraction can increase TMD risk, especially with factors like impaction, surgical difficulty, age, and sex. |
(TMD: temporomandibular disorder, TMR: third molar removal, TMJ: temporomandibular joint, RDC: research diagnostic criteria, ICD: International classification of diseases, 9th revision, VAS: visual analogue scale, DC: diagnostic criteria, PMMPS: preauricular and masticatory muscle pain symptoms, OR: odds ratio, CI: confidence interval, RR: risk ratio, NS: not significant)
Table 4
| Study | Study participation | Measurement of variables | Risk from non-response bias | Control of confounding | Reporting quality | Overall AXIS judgment |
|---|---|---|---|---|---|---|
| DeAngelis et al.21 (2009) | Moderate (sequential referrals, 60 small sample) | Standardized TMD exam (O) | Not reported (X) | Not adjusted (X) | Clear reporting of aims/results (O) | Moderate risk |
| Barbosa et al.20 (2016) | Large sample (1,381 students, good participation) | Validated RDC/TMD diagnostic tool (O) | Non-response bias not detailed (X) | Logistic regression controlled for sex and age (O) | Clear reporting (O) | Low-Moderate risk |
Table 5
| Study | Selection (max ★★★★) | Comparability (max ★★) | Outcome (max ★★★) | NOS score | Overall NOS judgment |
|---|---|---|---|---|---|
| Huang et al.18 (2008) | ★★★ (Representative Kaiser HMO cohort) | ★★ (Matched controls, adjusted for utilization) | ★☆ (Registry-based TMD diagnosis; misclassification possible) | 6/9 | Low-Moderate risk |
| Huang and Rue19 (2006) | ★★★ (Large Washington Dental Service cohort, n=34,491) | ★★ (Adjusted for sex, utilization, confounders) | ★☆ (Claims-based TMD diagnoses, possible under-reporting) | 6/9 | Low-Moderate risk |
| Munawar et al.17 (2016) | ★★ (Small university cohort, n=42) | ★ (Limited adjustment, no multivariate control) | ★☆ (Follow-up 6 months, outcomes via DC/TMD exam, low attrition) | 4/9 | Moderate-High risk |
| Uppgaard et al.23 (2024) | ★★★★ (Multisite RCT cohort-like sample, n=169) | ★★ (Randomization balanced confounders) | ★★★ (Longitudinal follow-up, validated screener, >95% retention) | 9/9 | Low risk |
Table 6
| Study | Total sample (n) | Pooled effect (RR/OR/MD) | 95% Confidence interval |
|---|---|---|---|
| Barbosa et al.20 (2016) | 1,381 university students | OR=1.30 (TMR vs. no TMR for TMD) | Not reported |
| DeAngelis et al.21 (2009) | 60 referrals for third molar extraction | Prevalence: 13.3% TMD-only; 23.3% mixed TMD+third molar | NA |
| Huang et al.18 (2008) | 4,434 (2,217 extraction vs. 2,217 controls) | RR=1.4 | 0.9-2.2 |
| Huang and Rue19 (2006) | 34,491 | Adjusted RR=1.6 | 1.3-2.0 |
| Gururaj et al.16 (2023) | 430 RCT (215 extraction vs. 215 control) | MD=96% symptom reduction in extraction group | Not reported |
| Munawar et al.17 (2016) | 42 (22 operative, 20 non-operative) | Incidence: trismus 92%, myofascial pain 69%, clicking 77% vs. control; 2 new TMD at 6 months | Not expressed as RR |
| Uppgaard et al.23 (2024) | 169 RCT | OR=3.44 for fully impacted molars predicting postoperative pain | 1.49-7.92 |
| Damasceno et al.22 (2020) | 7 clinical studies (hundreds-thousands pooled) | OR=1.81-2.15; RR=2.1 | Not consistent across studies |



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