Purpose: Radium-223 was associated with high incidence of non-vertebral fractures in patients with castration-resistant prostate cancer (CRPC). However, it is still unclear whether radium-223 may induce skeletal fragility regardless of other therapies for CRPC. We aimed at evaluating the prevalence, incidence, and determinants of vertebral fractures (VFs), i.e., the most frequent complication of skeletal fragility, in CRCP patients undergoing radium-223 therapy in the real-life clinical practice.
Methods: We retrospectively reviewed 49 CRPC patients with symptomatic bone metastases treated with radium-223. Patients received median number of four radium-223 doses (range: 2-6) and were followed-up for a median period of 11 months (range: 6-44). VFs were assessed by a quantitative morphometry using lateral images of spine 11C-Choline PET/CT, excluding from the analysis the vertebral bodies affected by bone metastases.
Results: Before radium-223 administration, 24 patients (49%) had VFs significantly associated with duration of androgen deprivation therapy (ADT; odds ratio 1.29) and previous abiraterone therapy (odds ratio 3.80). During radium-223 therapy, incident VFs occurred in 25% of patients, in relationship with prevalent VFs (hazard ratio 6.89) and change in serum total alkaline phosphatase values (hazard ratio 0.97), whereas the correlations with ADT and abiraterone therapy were lost. Noteworthy, the risk of VFs did not correlate with the therapeutic end points of radium-223.
Conclusions: This study provides a first evidence that in real-life clinical practice, radium-223 therapy may induce skeletal fragility with high risk of VFs, likely by inhibition of bone formation and independently of ADT and abiraterone therapy.
Keywords: Androgen deprivation therapy; Osteoporosis; Prostate cancer; Radium-223; Vertebral fractures.