THE ACTIVITY OF PEPTIDES OF THE CALCITONIN FAMILY IN BONE

Calcitonin was discovered over 50 yr ago as a new hormone that rapidly lowers circulating calcium levels. This effect is caused by the inhibition of calcium efflux from bone, as calcitonin is a potent inhibitor of bone resorption. Calcitonin has been in clinical use for conditions of accelerated bone turnover, including Paget's disease and osteoporosis; although in recent years, with the development of drugs that are more potent inhibitors of bone resorption, its use has declined. A number of peptides that are structurally similar to calcitonin form the calcitonin family, which currently includes calcitonin gene-related peptides (alpha CGRP and beta CGRP), amylin, adrenomedullin, and intermedin. Apart from being structurally similar, the peptides signal through related receptors and have some overlapping biological activities, although other activities are peptide specific. In bone, in vitro studies and administration of the peptides to animals generally found inhibitory effects on osteoclasts and bone resorption and positive effects on osteoblasts and bone formation. Surprisingly, studies in genetically modified mice have demonstrated that the physiological role of calcitonin appears to be the inhibition of osteoblast activity and bone turnover, whereas amylin inhibits osteoclast activity. The review article focuses on the activities of peptides of the calcitonin family in bone and the challenges in understanding the relationship between the pharmacological effects and the physiological roles of these peptides.