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The calcium-sensing receptor in bone metabolism: from bench to bedside and back

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Abstract

Summary

The calcium-sensing receptor (CaSR), a key player in the maintenance of calcium homeostasis, can influence bone modeling and remodeling by directly acting on bone cells, as demonstrated by in vivo and in vitro evidence. The modulation of CaSR signaling can play a role in bone anabolism.

Introduction

The calcium-sensing receptor (CaSR) is a key player in the maintenance of calcium homeostasis through the regulation of PTH secretion and calcium homeostasis, thus indirectly influencing bone metabolism. In addition to this role, in vitro and in vivo evidence points to direct effects of CaSR in bone modeling and remodeling. In addition, the activation of the CaSR is one of the anabolic mechanisms implicated in the action of strontium ranelate, to reduce fracture risk.

Methods

This review is based upon the acquisition of data from a PubMed enquiry using the terms “calcium sensing receptor,” “CaSR” AND “bone remodeling,” “bone modeling,” “bone turnover,” “osteoblast,” “osteoclast,” “osteocyte,” “chondrocyte,” “bone marrow,” “calcilytics,” “calcimimetics,” “strontium,” “osteoporosis,” “skeletal homeostasis,” and “bone metabolism.”

Results

A fully functional CaSR is expressed in osteoblasts and osteoclasts, so that these cells are able to sense changes in the extracellular calcium and as a result modulate their behavior. CaSR agonists (calcimimetics) or antagonists (calcilytics) have the potential to indirectly influence skeletal homeostasis through the modulation of PTH secretion by the parathyroid glands. The bone anabolic effect of strontium ranelate, a divalent cation used as a treatment for postmenopausal and male osteoporosis, might be explained, at least in part, by the activation of CaSR in bone cells.

Conclusions

Calcium released in the bone microenvironment during remodeling is a major factor in regulating bone cells. Osteoblast and osteoclast proliferation, differentiation, and apoptosis are influenced by local extracellular calcium concentration. Thus, the calcium-sensing properties of skeletal cells can be exploited in order to modulate bone turnover and can explain the bone anabolic effects of agents developed and employed to revert osteoporosis.

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Conflict of interest

Luisella Cianferotti, Ana Rita Gomes, Sergio Fabbri, and Annalisa Tanini declare that they have no conflict of interest. Maria Luisa Brandi declares that she has conflict of interest as consultant and recipient of grants from Amgen, Eli Lilly, MSD, Novartis, Roche, and Servier.

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Authors and Affiliations

  1. Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University of Florence, 50134, Florence, Italy

    L. Cianferotti, A. R. Gomes, S. Fabbri, A. Tanini & M. L. Brandi

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  1. L. Cianferotti
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  2. A. R. Gomes
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  3. S. Fabbri
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  4. A. Tanini
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  5. M. L. Brandi
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Correspondence to M. L. Brandi.

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Cianferotti, L., Gomes, A.R., Fabbri, S. et al. The calcium-sensing receptor in bone metabolism: from bench to bedside and back. Osteoporos Int 26, 2055–2071 (2015). https://doi.org/10.1007/s00198-015-3203-1

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  • DOI: https://doi.org/10.1007/s00198-015-3203-1

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