Does Drug Type Influence Surgical Outcome in MRONJ? A Comparison of Denosumab and Zoledronate

Abstract

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive therapy, and optimal surgical management remains challenging. Understanding whether drug type affects outcomes is clinically relevant for treatment planning. Purpose: The study purpose was to compare postoperative healing and reoperation between denosumab and zoledronate in surgically treated MRONJ. Center included MRONJ subjects treated surgically after exposure to denosumab or zoledronate; subjects with dual exposure, exposure to other antiresorptive agents, or insufficient follow-up data to ascertain study outcomes were excluded. Predictor Variable: The predictor variable was antiresorptive agent type (denosumab vs zoledronate). Main Outcome Variables: The primary outcome was therapeutic effect measured using time to complete clinical healing, defined as the time from surgery to complete mucosal coverage without exposed bone and no clinical evidence of infection; the secondary outcome was reoperation during follow-up, coded as yes or no. Covariates: Covariates included age, sex, indication, and duration of antiresorptive therapy, MRONJ stage and site, and surgical factors. Analyses: Kaplan-Meier/log-rank and Cox regression were used for healing, and logistic regression was used for reoperation. Results: A total of 90 subjects were included: denosumab, 61 (67.8%) and zoledronate, 29 (32.2%). The mean age was 70.5 +/- 10.7 years, and 79 (87.8%) were female. During a median follow-up of 10.5 months (interquartile range, 4 to 23), healing occurred in 76 subjects (84.4%). Median time to complete clinical healing was 3.0 months (95% CI, 2.0 to 4.0) for denosumab and 5.0 months (95% CI, 0.9 to 9.1) for zoledronate (log-rank P = .2). Antiresorptive agent type was not associated with time to complete clinical healing (adjusted hazard ratio, 1.20; 95% CI, 0.61 to 2.36; P = .6), whereas bone metastasis indication was associated with a lower hazard of healing (adjusted hazard ratio, 0.42; 95% CI, 0.20 to 0.89; P = .023). Reoperation occurred in 21 subjects (23.3%) and was not associated with antiresorptive agent type (adjusted odds ratio, 0.93; 95% CI, 0.21 to 4.07; P = .9), whereas bone metastasis indication and MRONJ stage 3 were associated with reoperation. Conclusions and Relevance: Outcomes after MRONJ surgery were more strongly associated with indication for antiresorptive therapy and MRONJ stage than with antiresorptive agent type, aligning with American Association of Oral and Maxillofacial Surgeons guidance emphasizing stage-based management and distinct clinical contexts across indications. (c) 2026 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 84:769-777, 2026