Risk of fracture following androgen receptor pathway inhibitors (ARPIs): A population-based study.

11164 Background: Androgen deprivation therapy is associated with an increased risk of fracture. ARPIs are widely used to manage advanced prostate cancer (PCa). However, there is limited long-term data on fracture risk following ARPIs and how the risk might vary with different health conditions. This study aims to fill these gaps. Methods: This study used the SEER-Medicare linked files to identify men diagnosed with PCa between 1/1/1999 and 12/31/2019 and who received abiraterone with prednisone (AAP) or enzalutamide (ENZA) between 1/1/2013 and 12/31/2020. The primary endpoint is the time to first fracture after the index date (first date of AAP or ENZA). The history of fracture was based on claims one year before the index date. Fine and Gray’s sub-distribution hazard model was used to estimate the effect of various risk factors. We used the cumulative incidence function to quantify fracture risk. Results: This study comprised 10,463 patients (6,037 with AAP and 4,426 with ENZA). Most patients were over 75 with a comorbidity score of 1 or higher. Among 1,445 patients who had a fracture the year before the index date, the risk of fracture after ARPI reached 50% (95% CI 47% - 53%) within 3 years, compared to 26% (95% CI 25%-27%) among those without a fracture. After adjusting for bone health agent use, comorbidities, and sociodemographic factors, a history of fracture was associated with 2.8 fold risk of fracture after AAP (RR=2.80, 95% CI 2.47 – 3.18) and 2.85 fold risk after ENZA (RR=2.85, 95% CI 2.45-3.30). Use of bone health agents within 3 months before the index date was associated with a 20-25% lower fracture risk. Conclusions: This large population-based study shows that the risk of fracture following ARPIs is substantial, especially among those who suffered a fracture before ARPIs. It is crucial to consider the history of fracture when making treatment choices and monitoring strategies. Better management of bone health is crucial for men treated with ARPIs.