Polygenic Risk Score as a Predictor of Bone Fracture or Osteoporosis in Prostate Cancer Patients Receiving Androgen Deprivation Therapy

Background The association between single nucleotide polymorphisms (SNPs) and fracture risk has been established in various studies. Androgen‐deprivation therapy (ADT) for prostate cancer, while extending survival, increases the risk of osteoporosis and bone fracture. This study aimed to assess the predictive value of polygenic risk scores (PRSs) on bone events among prostate cancer patients undergoing ADT. Methods We enrolled 24,778 male participants, including 903 prostate cancer patients treated at Taichung Veterans General Hospital. These patients were divided into ADT and non‐ADT groups. Nine PRSs related to bone mineral density from the PGS Catalog were tested and categorized into quartiles. Cox proportional hazards regression analysis was performed to evaluate the risk of bone fracture and osteoporosis between groups by PRS quartiles. Results Among the PRSs, PGS002632, PGS002681, and PGS001955 demonstrated the highest areas under the curve (AUCs) for predicting bone events. For PGS002632, the risk was significantly higher in the first quartile (Q1) compared to the fourth quartile (Q4) for patients receiving ADT (HR = 5.934, p = 0.0013), after adjusting for age and comorbidities. Furthermore, within the subgroup of prostate cancer patients in Q1 of PGS002632, the risk was higher for those receiving ADT compared to those not receiving ADT (HR = 3.698, p = 0.0093). Similar results were observed for PGS002681 and PGS001955. Conclusion This hospital‐based cohort study among Han Chinese highlights PRS as a potential biomarker for bone fracture and osteoporosis risk in prostate cancer patients initiating ADT. It provides a basis for personalized risk assessment and early intervention with bone protective strategies.