Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by products produced by tumors or indirectly through other nonmalignant cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Because these agents were shown to be effective in treating other diseases associated with increased bone resorption, including cancer-related hypercalcemia and Paget's disease of bone, studies were initiated to explore the use of bisphosphonates in patients with osteolytic bone metastases.