Calcium homeostasis is a key element in bone development and in the maintenance of normal bone architecture. Bone acts in conjunction with the kidneys and the parathyroid glands to maintain circulating calcium levels. In times of excess it functions as a reservoir, but it is also able to donate calcium to the body when circulating levels are low and its structure and mineral content vary accordingly. The calcium sensing receptor (CaR) in both the parathyroid glands and in the kidneys plays an important role in calcium homeostasis by regulating parathyroid hormone secretion and production of 1,25-dihydroxyvitamin D3, which among other functions co-ordinate skeletal calcium flux and therefore bone structure. However, fluctuations in local calcium concentrations within bone itself are also important. The function and activity of a number of bone cells is influenced by calcium and during periods of bone reabsorption local levels of calcium increase significantly beyond normal plasma concentrations. It therefore seems likely that bone contains a calcium sensing mechanism, but is it the CaR? Evidence for the involvement of the CaR in bone has come from a number of areas. CaR expression has been detected in a variety of bone cell types including osteoblasts, osteoclasts and their precursors and also chondrocytes. The CaR knockout mouse displays growth retardation, suggestive of a bone phenotype. However, it can be argued that the bone defects that this animal exhibits are as a consequence of generalised perturbations in calcium homeostasis. Additionally, osteoblasts from the CaR knockout animal remain responsive to calcium. More compelling evidence comes from studies that have demonstrated a direct effect of CaR agonists on bone and cartilage. Although this is still a controversial area, there is growing evidence that points to a CaR being important in bone development.
22 - 24 Mar 2004
British Endocrine Societies