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Is the calcium receptor a molecular target for the actions of strontium on bone?

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Abstract

The extracellular calcium-sensing receptor (CaR) plays key roles in maintaining extracellular calcium homeostasis by enabling several of the cells and tissues involved in this process to sense small changes in Ca2+ o and to respond with changes in cellular function that will restore Ca2+ o to its normal level. The chief cells of the parathyroid gland and the thyroidal C-cells, for example, respond to decreases in Ca2+ o with increased secretion of the Ca2+ o-elevating hormone, parathyroid hormone (PTH), and decreased secretion of the Ca2+ o-lowering hormone, calcitonin, respectively. The cells of the renal distal tubule are likewise capable of sensing Ca2+ o and respond to decreases in Ca2+ o with increased tubular reabsorption of Ca2+ and vice versa, alterations in tubular function that will contribute to normalization of Ca2+ o. The skeleton also plays key roles in maintaining Ca2+ o homeostasis and both osteoblasts and osteoclasts can sense Ca2+ o, with elevations in Ca2+ o promoting bone formation and inhibiting bone resorption. It has been suggested that Sr2+ could act on bone via the CaR; however, the molecular mechanisms through which Ca2+ o and Sr2+ o exert these actions on bone cells remain controversial. Therefore, identifying their molecular target(s) would have significant implications for the treatment of bone loss. Ideally, therapies should simultaneously inhibit bone resorption while stimulating bone formation. Administration of strontium produces exactly those effects. Previous studies with dispersed bovine parathyroid cells as well as a preliminary study using CaR-transfected Chinese hamster ovary (CHO) cells indicate that Sr2+ o is an agonist of the CaR, albeit with slightly lower efficacies and potencies than Ca2+ o. Given that Sr2+ o is distributed preferentially in bone, therefore, an action of this divalent cation on the CaR in bone cells represents one possible mechanism by which strontium ranelate, a new antiosteoporotic drug, exerts it skeletal actions in vivo.

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The author receives research support from the Institut de Recherches Internationales Servier.

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  1. Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA

    Edward M. Brown

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Brown, E.M. Is the calcium receptor a molecular target for the actions of strontium on bone?. Osteoporos Int 14 (Suppl 3), 25–34 (2003). https://doi.org/10.1007/s00198-002-1343-6

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