RANK Ligand-targeted Therapy: A Novel Approach to Prevent Bone Loss and Fractures in Men with Prostate Cancer

Abstract

Abstract Context The importance of bone loss associated with both prostate cancer (PCa) and its treatment is being increasingly recognised, and new options to manage this complication are in development. Objective To assess the impact of androgen-deprivation therapy (ADT) on bone and to outline recently reported and ongoing phase 3 studies of agents designed to prevent bone loss and fractures in men with PCa. Evidence acquisition This article is based on a presentation at an Amgen-sponsored satellite symposium held at the European Association of Urology Congress in Stockholm, Sweden, in March 2009. Evidence synthesis ADT for PCa is associated with bone loss and an increased fracture risk. Several bisphosphonates have been shown to improve bone mineral density (BMD) during ADT, but their effects on treatment-related fractures are unknown. Denosumab, a fully human monoclonal antibody to RANK Ligand, is being investigated for the management of bone loss associated with PCa. The results of a phase 3 randomised, placebo-controlled trial of denosumab to prevent bone loss and fractures during ADT in men with PCa have recently been reported. Compared with placebo, denosumab (60mg subcutaneously every 6 mo) significantly reduced the incidence of new vertebral fractures by 62% after 3 yr. Denosumab also increased BMD significantly at various skeletal sites, including the spine, hip, and wrist. Conclusions ADT decreases BMD and increases fracture risk in men with PCa. A recent phase 3 study has demonstrated that denosumab increases BMD and significantly reduces the risk of new vertebral fractures in men with PCa. Two ongoing phase 3 studies are evaluating denosumab for the prevention and treatment of bone metastases in men with castration-resistant prostate cancer.