Novel approaches to the management of bone metastases in patients with breast cancer.

Bone metastases appear frequently in patients with advanced breast cancer. They are associated with substantial morbidity and occasionally produce life-threatening complications. Systemic anticancer therapies (chemotherapy and hormonal therapies) represent the treatment of choice for these and other distant metastases from breast cancer. Aggressive use of prophylactic and therapeutic orthopedic surgery is warranted, especially for lesions in weight-bearing areas. Judicious use of external radiotherapy and bone-seeking radionuclides contributes to the control of pain and local control of lesions in strategic locations. In recent years, the development of osteoclast-inhibitory therapy added a new dimension to symptom control and prevention of skeletal complications. The bisphosphonates, clodronate, pamidronate, and zoledronic acid, are potent osteoclast inhibitors with marked clinical effects. They represent the drugs of choice for control of hypercalcemia of malignancy, and they are critical adjuvants to systemic anticancer therapy of metastatic disease. More recently, the development of recombinant osteoprotegerin and an anti-parathyroid hormone-related protein monoclonal antibody represent promising new options for the treatment of patients with bone metastases.