Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents

Introduction The incidence rate and risk factors of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate cancer patients with bone metastasis are not clear. Materials and Methods We retrospectively reviewed patients' records of prostate cancer patients with bone metastasis who were treated with zoledronic acid or denosumab between 1/Dec/2008 and 31/Mar/2019. ARONJ-free survival rate was analyzed with Kaplan-Meier analysis, and risk factors for ARONJ were analyzed with Cox proportional hazard model. Results We identified 124 and 67 patients treated with zoledronic acid and denosumab, respectively. Seventy-six patients were hormone sensitive, and 115 patients were castration resistant when they started bone-modifying agents (BMA). Twenty-eight patients developed ARONJ during the observation period (median: 23 months, range 1-130 months). Their number of doses of BMA ranged 3-69 (median: 21.5). The 2-year ARONJ-free survival rate was 91.1%, and the 5-year ARONJ-free survival rate was 72.5%. There was no significant difference in the incidence rate of ARONJ between zoledronic acid and denosumab. However, multivariate analysis revealed that use of denosumab (hazard ratio [HR] 3.67, 95% confidence interval [CI] 1.01-13.31;p = 0.0484), serum calcium < 9.2 mg/dL (HR 3.16, 95% CI 1.10-9.13;p = 0.033)), and concomitant or prior use of chemotherapeutic agents (HR 4.71, 95% CI 1.51-14.71;p = 0.0076) were independent risk factors for the development of ARONJ. Conclusion Almost one-quarter of patients had a risk of developing ARONJ within 5 years after starting BMA. Low serum calcium, use of chemotherapeutic agents, and use of denosumab might contribute to the development of ARONJ.