Calcitonin - A drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality
Calcitonin - A drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality
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DOI：
10.2165/00063030-200822030-00001
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发表时间：
2008-01-01
期刊：
影响因子：
6.8
通讯作者：
Christiansen, Claus
中科院分区：
文献类型：
--
作者：
Karsdal, Morten A.;Henriksen, Kim;Christiansen, Claus
绝经后骨质疏松症是由于骨吸收和骨形成之间的持续失衡，有利于骨吸收。越来越多的骨质疏松症治疗方法正在开发和上市。这些治疗方案之间存在一系列差异和相似之处，在开始治疗之前需要仔细评估。本文综述了降钙素对骨转换影响的体外、动物实验和临床试验数据，发现降钙素通过直接减少骨吸收而发挥其抗骨吸收作用，从而导致骨密度和骨强度的增加。此外，降钙素似乎主要靶向最活跃的破骨细胞，与大多数其他抗吸收剂相反，它不会减少破骨细胞的数量。最后，在人类中，与其他目前可用的抗再吸收剂相比，降钙素治疗在减弱再吸收的同时不会显著干扰骨形成。因此，我们推测，降钙素治疗将导致一个持续的积极骨平衡与其他抗骨吸收剂目前在市场上，从而在生理方式，导致改善骨质量。然而，口服制剂可以改善患者的接受性和依从性。目前，正在寻求几种不同的途径来确定最佳的口服制剂，其中基于5-CNAC的技术是最先进的。骨关节炎和骨质疏松症临床试验中有关于该制剂的有希望的临床数据，尽管抗骨折功效尚不清楚。
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.