A real‐world study on the prevalence and risk factors of medication related osteonecrosis of the jaw in cancer patients with bone metastases treated with Denosumab

AIM: Assessing the incidence of Medication Related Osteonecrosis of the Jaw (MRONJ) in cancer patients with bone metastases receiving Denosumab (Dmab) and identifying potential risk factors. METHODS: A retrospective observational study on consecutive cancer patients with bone metastases, who received at least one dose of Dmab and one follow‐up visit. MRONJ crude cumulative incidence (CCI) was estimated considering death without MRONJ as competing event. Multiple regression models were used to study the association between MRONJ incidence and potential risk factors: age, cancer diagnosis, previous bisphosphonates, dental treatments before starting Dmab, extraction or other dental treatment during Dmab, chemotherapy, hormone therapy, and antiangiogenic (AA) agents concurrent use. RESULTS: On 780 patients included (median follow‐up 17 months), 54% and 18% had, respectively, breast and prostate cancer. The mean number of Dmab administration was 12. Fifty‐six patients developed MRONJ with a 24‐ and a 48‐month crude cumulative incidence of 5.7% (95% Cl: 4.2%–7.8%) and 9.8% (95% CI: 7.6%–12.7%), respectively. Higher MRONJ incidence was significantly associated with middle aged group (>56 and ≤73), both at univariate and multivariate analysis (p = 0.029 and 0.0106). Dental treatments (Hazard Ratio [HR] = 3.67; p = 0.0001), dental extractions (HR = 23.40; p < 0.0001), and previous BP administration (HR = 2.62; p = 0.0024) were significantly associated with higher MRONJ incidence at multivariate Cox analysis. Although not statistically significant, MRONJ incidence was lower for patients receiving chemotherapy or hormone therapy and higher for those receiving AAs. CONCLUSIONS: The results confirm a clinically relevant incidence of Dmab‐induced MRONJ. Dental treatments, especially extraction, during and before Dmab, constitute a serious risk factor. The role of AA concurrent administration deserves further investigations.