Risk of fracture following androgen receptor pathway inhibitors in men with advanced prostate cancer

Abstract

This population-based study aimed to quantify fracture risk after ARPIs in PCa patients by pre-existing health conditions. Patients were identified from the SEER-Medicare files who received abiraterone with prednisone (AAP) or enzalutamide (ENZA) between 1/1/2013 and 12/31/2020. Health and fracture history were based on claims one year before ARPI with follow-up through 12/31/2020. The main outcome of the study was the cumulative fracture risk after first date of ARPI. Fine and Gray's sub-distribution hazard model was used to obtain adjusted relative risks with confounding factors. This study included 10,463 patients (6,037- AAP; 4,426-ENZA). The 3-year fracture risk after ARPI was high, exceeding 25% among those without a prior fracture. Among 1,445 men with a fracture the year before ARPI, 3-year fracture risk exceeded 50%, and remained high (above 44%) despite using bone health agents (BHA). A recent history of fracture was associated with a 2.84-fold fracture risk (aHR: 2.84, 95% CI 2.58-3.12). Pre-existing osteoporosis and a comorbidity score ≥ 2 were associated with 15% (aHR : 1.15, 95% CI 1.03-1.29) and 11% (aHR : 1.11, 95% CI 1.00 to 1.24) higher fracture risks. Bone health agent (BHA) use was associated with a 23% lower fracture risk (aHR: 0.77, 95% CI 0.70-0.83). Fracture risk after ARPI was high, exceeding 44% within 3 years in those with prior fractures despite BHA, suggesting limited benefit in patients with poor bone quality. Early identification and intervention for patients at high risk of fractures is critical.