Risk of medication-related osteonecrosis of the jaw during romosozumab treatment

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but clinically important adverse event in antiresorptive osteoporosis care. The most recently approved osteoporosis medication, romosozumab, has a dual mechanism, combining antiresorptive and osteoanabolic effects. Thus, concern exists regarding a possible risk for MRONJ with romosozumab, although current evidence is limited mainly to isolated case reports. We performed a retrospective new-user active comparator propensity score-matched cohort study in the TriNetX Global Collaborative Network comparing women treated with romosozumab vs. parathyroid hormone (PTH) analogs (teriparatide or abaloparatide). Women aged ≥ 18 years with no prior osteonecrosis, jaw inflammatory disease, oral/head-neck cancer, or radiation exposure and no recent exposure to chemotherapy were eligible. After 1:1 propensity score matching, 15,689 patients remained in each cohort. During 1 year of follow-up, MRONJ occurred in 11 romosozumab-treated patients and 12 PTH analog-treated patients (hazard ratio [HR] 0.89, 95% CI 0.39–2.01; log-rank p = 0.78). Absolute event rates were very low in both groups (0.070% vs. 0.076%). As expected, the positive control outcome of hypercalcemia occurred less often with romosozumab (HR 0.66, 95% CI 0.58–0.75). These real-world data do not indicate a detectable excess short-term MRONJ risk with romosozumab compared with PTH analogs over the approved treatment window, although modest differences cannot be excluded because events were rare.