The management of hypercalcemia of malignancy

Hypercalcemia (HCM) occurs in 10-15% of all malignancies, predominantly in patients with solid tumors. This metabolic complication leads to significant morbidity and impairment of quality of life. Recent insights into the pathophysiology of HCM include an understanding of the role of parathyroid-hormone-related peptide and several cytokines secreted by tumors. The osteoclast plays a central role as the final common pathway through which these hormones and cytokines act to cause bone lysis. These findings have led to the development of new treatment strategies. Foremost among these has been the introduction of agents such as the newer bisphosphonates and gallium nitrate, which are potent inhibitors of osteoclast-mediated bone resorption. The clinician can now choose from an array of therapeutic approaches based on a consideration of the mechanisms of action, individual clinical circumstances, efficacy, toxicities and costs of available agents. In addition to their use in the management of HCM, non-toxic drugs that effectively inhibit osteoclast function, such as the bisphosphonates, are playing an emerging role in the palliative treatment of the more common clinical problems of painful lytic bone metastases and osteoporosis.