Cumulative Incidence and Risk Factors for Anti-Resorptive Agent-Related Osteonecrosis of the Jaw during Long-Term Prostate Cancer Management

Abstract Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of anti-resorptive agent-related osteonecrosis of the jaw (ARONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of ARONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had ARONJ during the follow-up period (median, 19 months; interquartile range, 9–43 months). The 2-year, 5-year, and 10-year cumulative ARONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for ARONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93–11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of ARONJ (HR 0.08, 95% CI 0.01–0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13–11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68–15.2) were risk factors for stage 2 or more severe ARONJ. ARONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.