Serum vitamin D Levels in patients with medication-related osteonecrosis of the jaw: a systematic review and meta-analysis.

OBJECTIVES: To compare serum 25-hydroxyvitamin D [25(OH)D] levels between patients with medication-related osteonecrosis of the jaw (MRONJ) and antiresorptive-exposed controls. MATERIALS AND METHODS: Following PRISMA guidelines, PubMed, Scopus, Web of Science, and Embase were searched through September 2025 for studies including adults (≥ 18 years) treated with bisphosphonates or denosumab that reported 25(OH)D levels in MRONJ cases and exposed controls. Random-effects models generated standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity, influence and subgroup analyses, random-effects meta-regression, and publication bias (Egger’s and Begg’s tests) were assessed. RESULTS: Six studies (five case–control, one cohort; 184 MRONJ, 175 controls) met inclusion criteria. Mean serum 25(OH)D was 33.16 ± 4.27 ng/mL in MRONJ patients and 36.86 ± 5.02 ng/mL in controls. The SMD was − 0.06 (95% CI, − 0.51 to 0.39; p = 0.79) with heterogeneity (I² = 75.0%; p < 0.001). After exclusion of two influential studies, heterogeneity decreased to 0% and the SMD remained non-significant (− 0.11; 95% CI, − 0.36 to 0.15; p = 0.41). Subgroup analyses by indication/population (mixed osteoporosis plus oncologic versus exclusively oncologic) showed no significant differences. Meta-regression indicated that control sample size and bisphosphonate exposure duration in MRONJ groups were associated with effect size. The certainty of evidence for the analyzed outcome was very low. CONCLUSIONS: Postdiagnosis serum 25(OH)D levels appear similar in MRONJ patients and antiresorptive-exposed controls; however, the evidence is limited and of very low certainty, so conclusions should be interpreted cautiously. CLINICAL RELEVANCE: In antiresorptive-treated adults, serum 25-hydroxyvitamin D levels measured after diagnosis do not differ meaningfully between patients with MRONJ and exposed controls, suggesting vitamin D is unlikely to be a primary determinant of MRONJ occurrence but may still modify disease course. TRIAL REGISTRATION: CRD420251172147.