The calcium-sensing receptor in bone--mechanistic and therapeutic insights

The extracellular calcium-sensing receptor, CaSR, is a member of the G protein-coupled receptor superfamily and has a critical role in modulating Ca(2+) homeostasis via its role in the parathyroid glands and kidneys. New evidence suggests that CaSR expression in cartilage and bone also directly regulates skeletal homeostasis. This Review discusses the role of CaSR in chondrocytes, through which CaSR contributes to the development of the cartilaginous growth plate, as well as in osteoblasts and osteoclasts, through which CaSR has effects on skeletal development and bone turnover in young and mature animals. The interaction of skeletal CaSR activation with parathyroid hormone (PTH), which is secreted by the parathyroid gland, can lead to net bone formation in trabecular bone or net bone resorption in cortical bone. Allosteric modulators of CaSR are beneficial in some clinical conditions, with effects that are mediated by the ability of these agents to alter levels of PTH and improve Ca(2+) homeostasis. However, further insights into the action of CaSR in bone cells might lead to CaSR-based drugs that maximize not only the effects of the receptor on the parathyroid glands and kidneys but also on bone.