Drug and hormone effects on calcium release from bone.

The mobilization of calcium from the bone to the extracellular fluid proceeds in parallel with the dissolution of bone matrix, and is subject to the same influences. The role of circulating hormones has been discussed, and the importance of the skeleton as a store of calcium, even though skeletal calcium release is a relatively slow process in maturity. The major circulating hormones stimulating the processes are parathyroid hormone, 1,25-dihydroxyvitamin D3, and epidermal growth factor related substances. These represent three different classes of hormone with respect to their initial mechanisms of action. The most potent known hormonal inhibitor of bone resorption is the peptide, calcitonin, which acts directly upon the osteoclasts to inhibit their activity and generation. Local factors are undoubtedly important in the regulation of bone resorption, especially the prostaglandins. Prostaglandin E2 is the most potent bone resorber of the arachidonic acid metabolites, and is much more likely to be important locally than as a circulating factor especially in disease states such as metastatic bone cancer and arthritis. In understanding the ways in which drugs can influence bone mineral release it is important to appreciate how bone cells interact to resorb mineral and matrix. In this review the view is presented that cells of the osteoblast lineage (perhaps at the stage of osteocytes, or 'lining' cells) are the prime target of the resorbing hormones. Once having been acted upon, they initiate events which result in activation of osteoclasts. If this involves the passage of a message from osteoblast/osteocyte to osteoclast, it will be important to define this in further research.