Bone resorption and formation are normally linked and therefore maintain bone strength. When the metabolic linkage is altered, bone structural and material properties decline. Postmenopausal and glucocorticoidinduced osteoporosis, Paget's disease of bone, and fibrous dysplasia are some of the conditions in which there is high-turnover bone resorption, leading to bone with impaired structure susceptible to fracture. Low bone mineral density (BMD) occurs when the rate of resorption exceeds that of formation. High-turnover states ensue with disproportionately increased osteoclastic activity, resulting in increased resorption. Bisphosphonates interfere with osteoclast activity and thus decrease the rate of bone resorption. Similarly, metastatic disease of bone, especially the lytic phase, appears to be mediated by both osteoclastic resorption and other mechanisms. The use of bisphosphonates has dramatically changed the clinical course of some patients with cancer by decreasing the morbidity of skeletal involvement.