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.
Journal of the National Cancer Institute. 2026 Mar 07 [Epub ahead of print]
Grace Lu-Yao, Nikita Nikita, Scott W Keith, Krupa Gandhi, Amy L Shaver, Swapnil Sharma, Christina Steinbock-Malfer, Hushan Yang, Christopher Yang, Kevin K Zarrabi, Stephen J Freedland, William K Kelly
Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States., Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States., Division of Biostatistics and Bioinformatics, Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States., Department of Bioinformatics, Drexel University, Philadelphia, PA, United States., Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, United States.