Bisphosphonates in the treatment of bone metastases.

Bone metastases are one of the most common problematic complications of advanced cancers. In addition to causing significant pain, bone metastases often result in fractures and debilitation. Stimulation of osteoclast activity by factors secreted by tumor cells is believed be the primary mechanism of bone destruction. Bisphosphonates inhibit osteoclast-related bone resorption, and have become standard therapy in the treatment of hypercalcemia of malignancy and postmenopausal osteoporosis. More recently, bisphosphonates have been shown to decrease pain and skeletal fractures associated with bone metastases. Structural changes in bisphosphonates influence their relative potency as well as other potentially beneficial effects such as inhibition of tumor growth factors, alteration of adhesion molecules, and apoptosis of tumor cells.