Background: Medication-related osteonecrosis of the jaw (MRONJ) remains a challenging complication in osteoporotic patients receiving denosumab (Dmab), particularly following dentoalveolar surgery. Although timing of surgical intervention has been proposed as a modifiable risk factor, evidence defining an optimal treatment window remains limited.

Methods: We conducted a retrospective cohort study of 258 osteoporotic patients receiving Dmab who attended a tertiary oral and maxillofacial surgery center between 2013 and 2023. Patient-level analyses were complemented by intervention-level analyses of 185 dentoalveolar procedures performed in 91 patients. Multivariable logistic regression and generalized estimating equation models were used to identify independent predictors of MRONJ.

Results: MRONJ developed in 14 patients (5.43% of the overall cohort). All cases occurred following dentoalveolar procedures performed within three months of the last Dmab injection. A longer interval between Dmab administration and surgery was independently associated with a significantly reduced risk of MRONJ (OR 0.35, 95% CI 0.16-0.77; P=0.0089). Prolonged antiresorptive therapy duration also remained an independent risk factor (OR 1.33, 95% CI 1.07-1.65; P=0.0101). No specific dentoalveolar procedure demonstrated an independent association with MRONJ development after adjustment.

Conclusions: Surgical timing appears to be the principal modifiable determinant of MRONJ risk in osteoporotic patients treated with denosumab. Our findings suggest that avoiding dentoalveolar surgery during the first three months after Dmab administration and, when clinically feasible, delaying intervention until at least four months after the last injection may substantially reduce MRONJ risk while minimizing the risk of rebound vertebral fractures associated with prolonged treatment interruption. These findings provide clinically relevant guidance for coordinating care between oral and maxillofacial surgeons and osteoporosis specialists.

Daya Masri, DMD, is a senior resident in the Department of Oral and Maxillofacial Surgery at Rabin Medical Center (Beilinson Hospital), Petah Tikva, Israel. He serves as the head of the department's dedicated MRONJ clinic and is actively involved in the management of complex jaw reconstruction cases in osteoporotic & oncology patients. His clinical and research interests focus on medication-related osteonecrosis of the jaw (MRONJ), and he has authored more than 30 peer-reviewed scientific publications in the field. Dr. Masri also serves as a lecturer in the Oral and Maxillofacial Surgery curriculum at the Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University.