Osteoclast-targeted therapy for prostate cancer.

Skeletal complications are a major cause of morbidity in men with metastatic prostate cancer. Bone metastases cause pain, fractures, spinal-cord compression, and ineffective hematopoiesis. Men without bone metastases are also at risk for skeletal complications. Androgen deprivation therapy (ADT), the mainstay of treatment for metastatic prostate cancer and a routine part of the management for many men with nonmetastatic prostate cancer, decreases bone mineral density, and increases fracture risk. Pathological osteoclast activation plays a central role in both disease and treatment-related skeletal morbidity. Bisphosphonates, potent inhibitors of osteoclast activity, are now an important part of the management for many men with prostate cancer. Zoledronic acid, a potent intravenous bisphosphonate, decreases the risk of skeletal complications in men with hormone-refractory prostate cancer and bone metastases. Zoledronic acid and pamidronate preserve bone mineral density in men receiving ADT for nonmetastatic prostate cancer. Ongoing clinical trials will evaluate the role of osteoclast-targeted therapy in other settings including prevention of treatment-related fractures, prevention of bone metastases in men with high-risk nonmetastatic prostate cancer, and prevention of skeletal complications in men with hormone-sensitive metastatic disease.