Should bisphosphonates be the treatment of choice for metastatic bone disease?

Bone metastases commonly occur in cancer patients, most frequently in patients with breast and prostate cancers, and are associated with considerable morbidity. Cancer cells secrete a number of paracrine factors that stimulate osteoclast function, resulting in osteolysis. Bisphosphonates are potent inhibitors of both normal and pathologic osteolysis, localizing preferentially to sites of active bone formation and resorption. Clinical studies have shown that long-term bisphosphonate treatment in patients with breast cancer and multiple myeloma decreases skeletal morbidity, skeletal-related events, pain, and improves quality of life. On the basis of the available clinical evidence, bisphosphonates should be part of the standard treatment for breast cancer and multiple myeloma. Currently, there is insufficient data to recommend their routine use for other types of tumors. Preliminary evidence indicates that bisphosphonates may prolong survival in cancer patients, but this needs to be confirmed in controlled clinical trials. Bisphosphonate treatment should start as soon as bone metastases have been identified and be continued for as long as they are a significant clinical problem. At present, the adjuvant role of bisphosphonates is unproven. The new third-generation agents in clinical development, ibandronate and zoledronate, should lead to improvements in therapy compared with current treatment regimens. Improvement in treatment could also be provided by better selection of patients for therapy.