The pharmacology and therapeutic utility of bisphosphonates.

Bisphosphonates have clinical application in diseases associated with increased bone turnover that inhibit osteoclast-mediated bone resorption by direct and indirect actions on osteoblasts and macrophages. Bisphosphonates are the treatment of choice for Paget's disease of bone, in which they return to normal the increased rate of bone turnover and slow radiographic disease progression. The agents reduce hypercalcemia associated with malignancy, and may reduce bone pain and prevent radiographic progression of metastatic bone disease. In patients with postmenopausal osteoporosis, they prevent further bone loss and reduce fracture rates. The drugs also ameliorate osteoporosis associated with long-term corticosteroid treatment. Bisphosphonates are well tolerated; gastrointestinal disturbances are the most common adverse events. Potential bone mineralization defects that occur with first-generation bisphosphonates are not of concern with therapeutic doses of newer ones.