Association of Total and Bioavailable Vitamin D With Medication-Related Osteonecrosis of the Jaws: A Case-Control...

Antiresorptive agent (ARA) therapy may cause medication-related osteonecrosis of the jaw (MRONJ), following dentoalveolar surgery. Vitamin D, an essential element for bone metabolism, may be a risk factor associated with MRONJ.

The study purpose was to measure association between total 25-hydroxyvitamin D (25(OH)D) and bioavailable 25(OH)D and the risk of MRONJ.

This case-control study evaluated patients with established MRONJ and at-risk controls, using prospectively collected clinical and biochemical data at Ankara University between October 2023 and July 2025. Adults receiving ARA were included as MRONJ cases requiring sequestrectomy or as at-risk controls undergoing tooth extraction.

The predictor variables were vitamin D measures: including total 25(OH)D (ng/mL) and bioavailable 25(OH)D (ng/mL).

The primary outcome variable was MRONJ status. Cases were defined according to American Association of Oral and Maxillofacial Surgeons criteria for MRONJ. Controls were at-risk patients that have been defined as asymptomatic patients, with a history of ARA use with no apparent necrotic bone, according to American Association of Oral and Maxillofacial Surgeons staging criteria.

The covariates were age, sex, duration of ARA therapy (years), systemic diseases, vitamin D supplementation, vitamin D-binding protein, and albumin.

Group comparisons, correlations, and logistic regression were performed; receiver operating characteristic curves determined discrimination. A P value <.05 was considered statistically significant in all analyses.

Fifty-six adults with ARA use history were enrolled: 20 (36%) MRONJ cases and 36 (64%) at-risk controls. Cases had borderline significantly lower total 25(OH)D and bioavailable vitamin D levels than controls (P = .05 for both). Multivariable models showed independent associations for vitamin D metrics: total 25(OH)D (OR: 0.94; 95% CI, 0.89 to 0.98; P = .01) and bioavailable vitamin D (OR: 0.93; 95% CI, 0.88 to 0.98; P = .01). Receiver operating characteristic analysis revealed good diagnostic accuracy for total 25(OH)D and bioavailable vitamin D (area under the curve: 0.86; 95% CI: 0.75 to 0.96; P < .001 and .85; 95% CI: 0.75-0.96; P < .001, respectively).

Lower total and bioavailable vitamin D levels were independently associated with MRONJ. Both total and bioavailable vitamin D demonstrated comparable discriminatory performance; however, bioavailable vitamin D may enhance individualized risk stratification, while total 25(OH)D offers practical implementation.