title: Calcium metabolism & hypercalcemia in adults.
abstract: Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.
authors.affiliation: Department of Surgical & Gastroenterological Sciences, University of Padua, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy. flumachi@unipd.it
authors.forename: F
authors.initials: F
authors.lastname: Lumachi
authors.forename: R
authors.initials: R
authors.lastname: Motta
authors.forename: D
authors.initials: D
authors.lastname: Cecchin
authors.forename: S
authors.initials: S
authors.lastname: Ave
authors.forename: V
authors.initials: V
authors.lastname: Camozzi
authors.forename: S M M
authors.initials: SM
authors.lastname: Basso
authors.forename: G
authors.initials: G
authors.lastname: Luisetto
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D049950:Hyperparathyroidism, Primary / Q000150:complications; D000090265:Klotho Proteins; D009369:Neoplasms / Q000150:complications; D010281:Parathyroid Hormone / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D053245:RANK Ligand; D044168:Receptor, Parathyroid Hormone, Type 1; D044169:Receptors, Calcium-Sensing; D050916:TRPV Cation Channels; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium