Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality.

Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment options, and these need to be carefully evaluated before the initiation of treatment. This article summarizes data from in vitro and animal studies, as well as clinical trials, on the effect of calcitonin on bone turnover. Calcitonin was found to exert its antiresorptive effects via directly reducing osteoclastic resorption, and thus leads to an increase in bone mineral density and bone strength. Furthermore, calcitonin appears to mainly target the most active osteoclasts, and in contrast to most other antiresorptive agents it does not reduce the number of osteoclasts. Finally, in humans, while attenuating resorption, calcitonin treatment does not interfere markedly with bone formation, in contrast to other currently available antiresorptive agents. Thus, we speculate that calcitonin treatment will lead to a continuously positive bone balance in contrast with other antiresorptive agents currently on the market and thereby, in a physiologic manner, result in improved bone quality. Calcitonin is currently only available in injectable and nasal formulations. An oral formulation may, however, improve patient acceptance and compliance. Currently, several different routes are being pursued to identify an optimal oral formulation, of which the technology based on 5-CNAC is the most advanced. There are promising clinical data available for this formulation from both osteoarthritis and osteoporosis clinical trials, although the antifracture efficacy is not yet known.