Natural history and treatment of bone complications in prostate cancer

Bone metastases are highly prevalent in patients with prostate cancer, and they commonly present a therapeutic challenge. The natural history of prostatic bone metastases is characterized by skeletal morbidity, often producing distressing symptoms for individual patients and reducing patient autonomy and mobility. These bone metastases are usually radiologically osteoblastic, but there is also a strong osteolytic component as evidenced by marked increases in bone resorption markers. Malignant bone lesions can reduce the structural integrity of the skeleton, resulting in skeletal complications such as pathologic fracture, spinal cord compression, and severe bone pain, which adversely affect quality of life. Preclinical and clinical studies have provided insight into the pathophysiology of malignant bone disease from prostate cancer and suggest that bone-directed therapies, including radionuclides, endothelin-1 antagonists, and bisphosphonates, may provide both palliative and therapeutic benefits. Clinical investigations with these agents are underway in patients with prostate cancer to gain insight into the pathophysiology of bone metastases and to evaluate the role of bone-specific therapies in treating and preventing bone metastases.