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

To compare serum 25-hydroxyvitamin D [25(OH)D] levels between patients with medication-related osteonecrosis of the jaw (MRONJ) and antiresorptive-exposed controls. 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. 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. 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. 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. CRD420251172147.