Whitfield J F, Morley P, Willick G E
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Drugs Aging. 1999 Aug;15(2):117-29. doi: 10.2165/00002512-199915020-00005.
As populations age in the world's 7 major pharmaceutical markets, an increasing number of men and women, but especially women during their first postmenopausal decade, are falling victim to a bone disease that can result in hospitalisation, disability and death. This disease is osteoporosis. Indeed, by the year 2007, as many as 153,000,000 people will have experienced at least some significant osteopenia, if not osteoporosis. Although there are many different drugs, such as calcitonin, the bisphosphonates, estrogen and selective estrogen receptor modulators, that can slow or even stop further bone loss, there are currently few that can replace already lost bone by directly stimulating bone growth. However, a family of potent bone-building (or bone-anabolic) peptides is currently undergoing clinical development. These are the first-generation 84-amino acid native parathyroid hormone (PTH) and its 34- to 38-amino acid N terminal fragments, and the potent second-generation mini-PTHs. In this article, we briefly summarise what has so far been learned about how these molecules stimulate the production of new biomechanically strong bone in animals and humans.
在全球7个主要制药市场,随着人口老龄化,越来越多的男性和女性,尤其是绝经后的首个十年中的女性,正成为一种可能导致住院、残疾甚至死亡的骨病的受害者。这种疾病就是骨质疏松症。事实上,到2007年,多达1.53亿人将至少经历某种程度的明显骨质减少,即便不是骨质疏松症。虽然有许多不同的药物,如降钙素、双膦酸盐、雌激素和选择性雌激素受体调节剂,可减缓甚至阻止进一步的骨质流失,但目前能够通过直接刺激骨生长来替代已流失骨质的药物却很少。然而,一族强效的促骨生成(即骨合成代谢)肽目前正处于临床开发阶段。这些包括第一代含84个氨基酸的天然甲状旁腺激素(PTH)及其含34至38个氨基酸的N端片段,以及强效的第二代微型PTH。在本文中,我们简要总结了目前在动物和人类中关于这些分子如何刺激生成新的具有生物力学强度的骨方面所了解到的情况。