Risk of Fracture Following Androgen Receptor Pathway Inhibitors in Men With Advanced Prostate Cancer
Document Type
Article
Publication Date
7-1-2026
Abstract
BACKGROUND: This population-based study aimed to quantify fracture risk after androgen receptor pathway inhibitors in advanced prostate cancer patients by preexisting health conditions.
METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results-Medicare files who received abiraterone acetate with prednisone or enzalutamide between January 1, 2013, and December 31, 2020. Health and fracture history were based on claims 1 year before androgen receptor pathway inhibitor with follow-up through December 31, 2020. The main outcome of the study was the cumulative fracture risk after first date of androgen receptor pathway inhibitor. Fine and Gray subdistribution hazard model was used to obtain adjusted relative risks with confounding factors.
RESULTS: This study included 10 463 patients (6037 treated with abiraterone acetate with prednisone; 4426 treated with enzalutamide). The 3-year fracture risk after androgen receptor pathway inhibitor was high, exceeding 25% among those without a prior fracture. Among 1445 men with a fracture the year before androgen receptor pathway inhibitor, 3-year fracture risk exceeded 50% and remained high (above 44%) despite using bone health agents. A recent history of fracture was associated with a 2.84-fold fracture risk (adjusted hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 2.58 to 3.12). Preexisting osteoporosis and a comorbidity score of 2 or higher were associated with 15% (adjusted HR = 1.15, 95% CI = 1.03 to 1.29) and 11% (adjusted HR = 1.11, 95% CI = 1.00 to 1.24) higher fracture risks. Bone health agent use was associated with a 23% lower fracture risk (adjusted HR = 0.77, 95% CI = 0.70 to 0.83).
CONCLUSIONS: Fracture risk after androgen receptor pathway inhibitor was high, exceeding 44% within 3 years in those with prior fractures despite bone health agents, suggesting limited benefit in patients with poor bone quality. Early identification and intervention for patients at high risk of fractures are critical.
Recommended Citation
Lu-Yao, Grace; Nikita, Nikita; Keith, Scott W.; Gandhi, Krupa; Shaver, Amy L.; Sharma, Swapnil; Steinbock-Malfer, Christina; Yang, Hushan; Yang, Christopher; Zarrabi, Kevin K.; Freedland, Stephen J.; and Kelly, William K., "Risk of Fracture Following Androgen Receptor Pathway Inhibitors in Men With Advanced Prostate Cancer" (2026). Kimmel Cancer Center Faculty Papers. Paper 182.
https://jdc.jefferson.edu/kimmelccfp/182
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
41795824
Language
English
Comments
This article is the author’s final published version in Journal of the National Cancer Institute, Volume 118, Issue 7, 2026, Pages 1290-1298.
The published version is available at https://doi.org/10.1093/jnci/djag061. Copyright © The Author(s) 2026.