Clinical characteristics of medication-related osteonecrosis of the jaw in breast cancer patients receiving zoledronic acid versus denosumab: a retrospective cohort study

BACKGROUND: Breast cancer is the most common malignancy in women worldwide, and bone-targeting agents (BTAs) - particularly zoledronic acid and denosumab - are widely administered for bone metastasis, carrying a recognized risk of medication-related osteonecrosis of the jaw (MRONJ) with reported incidence rates of 1-15% in oncologic populations. Drug-dependent differences in MRONJ characteristics, anatomical distribution, and the causal role of dentoalveolar procedures remain incompletely characterized in breast cancer patients. METHODS: This single-center retrospective cohort study included 101 breast cancer patients diagnosed with MRONJ per 2022 AAOMS criteria, who received zoledronic acid (n = 66) or denosumab (n = 35) exclusively at this institution between January 2009 and December 2025. All diagnoses were confirmed by a single board-certified oral and maxillofacial surgeon. Between-group comparisons were performed using the Mann-Whitney U, chi-square, and Fisher's exact tests as appropriate. RESULTS: Cumulative BTA dose count at MRONJ onset did not differ significantly between groups (mean 38.9 vs. 25.7; p = 0.076). The denosumab group developed MRONJ at an older mean age than the zoledronic acid group (59.5 vs. 55.7 years; p = 0.013). A significant drug-dependent anatomical difference was observed: mandibular predominance in the zoledronic acid group (59.1%) versus maxillary predominance in the denosumab group (54.3%; p = 0.015). The majority of patients developed MRONJ without prior dentoalveolar procedures (53.0% zoledronic acid; 65.7% denosumab). Periodontal disease prevalence was comparable between groups (60.5%; p = 1.000). CONCLUSION: Cumulative injection count alone does not reliably predict MRONJ onset in oncologic populations. The majority of cases arose without prior dentoalveolar procedures, challenging the paradigm of tooth extraction as the primary causative trigger. A drug-dependent MRONJ predilection in jaws- mandibular in zoledronic acid users, maxillary in denosumab users - warrants validation in larger prospective cohorts.