title: Cancer-induced hypercalcemia.
abstract: Cancer-induced hypercalcemia (CIH) occurs in 5% to 30% of patients with cancer during the course of their disease, depending on the type of tumor. This review provides information on the pathophysiology and treatment of CIH. Enhanced bone resorption is the primary cause of CIH and the release of tumor-derived mediators induces this increase in osteoclast-mediated resorption. The interactions between osteoclasts and cancer cells are mainly mediated by parathyroid hormone-related protein (PTHrP), that activates osteoblasts to produce receptor activator of nuclear factor-kappa ligand (RANKL) and osteoclast precursors, with subsequent bone osteolysis. Low parathyroid hormone serum levels together with high calcium levels in a cancer patient may suggest a CIH. There are two different therapeutic approaches for treating CIH, to increase the urinary excretion of calcium, or to inhibit osteoclastic bone resorption, RANKL or the action of PTHrP. In patients with CIH the first step of therapy is usually to restore renal function which is often impaired due to dehydration. Bisphosphonates administration is at present the main-stay of treatment, while calcitonin, gallium nitrate and mithramycin have limited activity and several side-effects. Anti-RANKL therapy (denosumab) and antibodies against PTHrP are promising therapies, but their clinical use should be further explored to more clearly document the effects.
authors.affiliation: University of Padua, School of Medicine, Department of Surgical and Gastroenterological Sciences, via Giustiniani 2, 35128 Padova, Italy. flumachi@unipd.it
authors.forename: Franco
authors.initials: F
authors.lastname: Lumachi
authors.forename: Antonella
authors.initials: A
authors.lastname: Brunello
authors.forename: Anna
authors.initials: A
authors.lastname: Roma
authors.forename: Umberto
authors.initials: U
authors.lastname: Basso
mesh_terms: D004164:Diphosphonates / Q000627:therapeutic use; D006801:Humans; D006934:Hypercalcemia / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D009369:Neoplasms / Q000150:complications*; D044162:Parathyroid Hormone-Related Protein / Q000097:blood
chemical_list: D004164:Diphosphonates; D044162:Parathyroid Hormone-Related Protein