Fracture Risk in Men with Metastatic Prostate Cancer Treated With Radium-223

Radium-223 increases the risk of fracture in combination with abiraterone and prednisolone. The fracture risk of radium-223 monotherapy is unclear. This prospective study assessed fracture incidence in men treated with radium-223 matched with a cohort that did not have radium-223. We identified 74 new fractures in 20 patients receiving radium-223. Most fractures occurred in bones without apparent metastases. Bone health agents should be mandatory before starting radium-223. 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: This was a prospective, multicenter phase II study of radium-223 in 36 men with mCRPC and a reference cohort ( n = 36) matched for fracture risk and not treated with radium-223. Bone fractures were assessed using whole-body magnetic resonance imaging. The pr imary outcome was r isk of new fractures. Results: Thirty-six patients were treated with up to six 4-week cycles of radium-223. With a median follow-up of 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% (95% confidence interval, 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 a median follow-up of 24 months. Across both cohorts, 67% of all fractures 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 the risk of fragility fractures.

Automated summary

Radium-223 combined with abiraterone and prednisolone increases the risk of fracture, while the fracture risk of radium-223 monotherapy is unclear. A prospective study found that men treated with radium-223 are at risk of fractures, especially in bones without metastases, and should receive bone health agents before treatment.