Fracture risk in men with metastatic prostate cancer treated with radium-223

Abstract Background Radium-223 is a bone-seeking, alpha-emitting radionuclide used in metastatic castration resistant prostate cancer (mCRPC). Radium-223 increases the risk of fracture when used in combination with abiraterone and prednisolone. The risk of fracture in men receiving radium-223 monotherapy is unclear. Patients and Methods Prospective, multicentre phase II study of radium-223 in 36 men with mCRPC, and a reference cohort (n=36), matched for fracture risk, not treated with radium-223. Bone fractures were assessed using whole body MRI (WB MR). The primary outcome was risk of new fractures. Results 36 patients were treated with up to six 4-weekly cycles of radium-223. With a median follow-up 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% (95% CI: 35.3-71.6) at 12 months.  On multivariate analysis, prior corticosteroid use was associated with risk of fracture.  In the reference cohort (n=36), 16 new fractures were identified in 12 patients over median 24 months follow-up. 67% of all fractures across both cohorts occurred at uninvolved bone. Conclusions Men with mCRPC, and particularly those treated with radium-223, are at risk of fracture. They should receive a bone health agent to reduce risk of fragility fractures.