Parathyroids, bone and mineral metabolism: Edited by Vin TangprichaMechanisms and treatment of hypercalcemia of malignancyClines, Gregory A.Author Information aDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham bVeterans Affairs Medical Center, Birmingham, Alabama, USA Correspondence to Gregory A. Clines, MD, PhD, Assistant Professor of Medicine and Cell Biology, Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, 1808 7th Avenue South, BDB 730 Birmingham, AL 35294-0012, USA Tel: +1 205 934 4187; fax: +1 205 975 9372; e-mail: [email protected] Current Opinion in Endocrinology & Diabetes and Obesity: December 2011 - Volume 18 - Issue 6 - p 339-346 doi: 10.1097/MED.0b013e32834b4401 Buy Metrics Abstract Purpose of review Hypercalcemia of malignancy is a common paraneoplastic syndrome and a frequent complication of advanced breast and lung cancer, and multiple myeloma. The development of this malignancy complication often purports a poor prognosis. Thorough evaluation to establish the cause of hypercalcemia is essential because some patients may actually have undiagnosed primary hyperparathyroidism. Recent findings Production of humoral factors by the primary tumor, collectively known as humoral hypercalcemia of malignancy (HHM), is the mechanism responsible for 80% of cases. The vast majority of HHM is caused by tumor-produced parathyroid hormone-related protein followed by infrequent tumor production of 1,25-dihydroxyvitamin D and parathyroid hormone. The remaining 20% of cases are caused by bone metastasis with consequent bone osteolysis and release of skeletal calcium. Key therapies are saline hydration to promote calciuresis and bisphosphonates to reduce pathologic osteoclastic bone resorption. Calcitonin and glucocorticoids, especially in 1,25-dihydroxyvitamin D-mediated HHM, also have calcium-lowering effects. Summary Recent discoveries on mechanisms of malignancy-associated hypercalcemia highlight the critical role of the osteoclast. Bisphosphonates and other novel therapies being evaluated in clinical trial target this bone-resorbing cell type and provide effective and durable serum calcium reduction. Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.