Treatment and prevention of bone complications from prostate cancer

Bone metastases and skeletal complications are major causes of morbidity in prostate cancer patients. Despite the osteoblastic appearance of bone metastases on imaging studies, patients have elevated serum and urinary markers of bone resorption, indicative of high osteoclast activity. Increased osteoclast activity is independently associated with higher risk of subsequent skeletal complications, disease progression, and death. Osteoclast-targeted therapies are therefore a rational approach to reduction of risk for disease-related skeletal complications, bone metastases, and treatment-related fractures. This review focuses on recent advances in osteoclast-targeted therapy in prostate cancer. Bisphosphonates have been extensively studied in men with prostate cancer. Zoledronic acid significantly decreased the risk of skeletal complications in men with castration-resistant prostate cancer and bone metastases, and it is FDA-approved for this indication. Denosumab is a human monoclonal antibody that binds and inactivates RANKL, a critical mediator of osteoclast differentiation, activation, and survival. Recent global phase 3 clinic trials demonstrated an emerging role for denosumab in the treatment of prostate cancer bone metastases and prevention of fractures associated with androgen deprivation therapy.