New opportunities in the management of prostate cancer–related bone complications

Bone metastases and skeletal events related to bone loss are common complications of prostate cancer and its treatment with androgen deprivation therapy. Skeletal-related events, particularly fractures, reduce functional independence and overall survival. Strategies to prevent cancer-related bone loss and restore or maintain bone integrity are thus critical in managing patients with prostate cancer. Management of bone metastases includes radiotherapy, surgery, vertebroplasty, kyphoplasty, and pharmacotherapy with bisphosphonates. Intravenous pamidronate and zoledronic acid are among the bisphosphonates that have been most extensively studied in the treatment of bone metastases. Toxicities associated with bisphosphonates include acute-phase reactions, nephrotoxicity, and osteonecrosis of the jaw. Targeted therapies for prostate cancer–related bone metastases are rapidly being developed. Agents in early stages of clinical development include denosumab, odanacatib, atrasentan, and other mediators of osteoclast activity. Increased use of androgen deprivation therapy for prostate cancer and at earlier stages in the disease course requires that clinicians understand the implications for greater bone loss and monitor patients appropriately. Skeletal morbidity has become an increasing concern, as men survive this disease for longer periods of time. In the absence of any drug treatments specifically approved for the prevention of bone loss from cancer treatment, management is guided by available data from studies showing reduced bone loss with the use of bisphosphonates and selective estrogen-receptor modulators, as well as with emerging agents in patients receiving androgen deprivation therapy.