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生长激素和胰岛素样生长因子-1作为骨质疏松症的治疗药物。

GH and IGF-I as therapeutic agents for osteoporosis.

作者信息

Agnusdei D, Gentilella R

机构信息

Eli Lilly and Co., Florence, Italy.

出版信息

J Endocrinol Invest. 2005;28(8 Suppl):32-6.

Abstract

Current strategies for the treatment of osteoporosis rely almost exclusively on agents whose pharmacological actions are primarily antiresorptive. There is, therefore, growing interest in developing agents able to stimulate bone formation, such as GH and IGF-I, which play an important role in bone metabolism, being essential for the development and growth of the skeleton and for the maintenance of bone mass. Furthermore, the decline in GH/IGF-I axis with aging, is correlated with the increased risk of osteoporosis and fragility fractures in elderly population. Several studies investigated the potential of GH and/or IGF-I as therapeutic agents in osteoporotic patients (post-menopausal women and idiopathic osteoporotic men), showing a clear correlation between the used GH dosage (and the obtained IGF-I plasmatic levels) and the increase in bone turnover markers and/or bone mineral density (BMD) at different skeletal sites. In particular, the use of IGF-I/IGFBP-3 complex seems to be very useful and safe in older women with recent hip fracture. Also the possibility of combining GH/IGF-I treatment with antiresorptive drugs (such as calcitonin and alendronate) has been explored, showing controversial results on BMD at different skeletal sites. In summary, based on the current evidence, it is clear that circulating GH and IGF-I are critical for skeletal modeling, bone acquisition and age related bone loss. Nevertheless, controlled studies with fracture incidence as endpoints are needed to fully assess the potential of these bone anabolic agents in the treatment of osteoporosis.

摘要

目前骨质疏松症的治疗策略几乎完全依赖于其药理作用主要为抗吸收的药物。因此,人们对开发能够刺激骨形成的药物越来越感兴趣,如生长激素(GH)和胰岛素样生长因子-I(IGF-I),它们在骨代谢中起重要作用,对骨骼的发育和生长以及骨量的维持至关重要。此外,随着年龄增长,GH/IGF-I轴功能下降与老年人群骨质疏松症和脆性骨折风险增加相关。多项研究调查了GH和/或IGF-I作为治疗骨质疏松症患者(绝经后妇女和特发性骨质疏松症男性)药物的潜力,结果表明所用GH剂量(以及所获得的IGF-I血浆水平)与不同骨骼部位骨转换标志物和/或骨矿物质密度(BMD)的增加之间存在明显相关性。特别是,IGF-I/IGFBP-3复合物的使用在近期发生髋部骨折的老年女性中似乎非常有用且安全。人们还探索了将GH/IGF-I治疗与抗吸收药物(如降钙素和阿仑膦酸盐)联合使用的可能性,结果显示在不同骨骼部位的BMD方面存在有争议的结果。总之,根据目前的证据,很明显循环中的GH和IGF-I对骨骼建模、骨量获取以及与年龄相关的骨质流失至关重要。然而,需要以骨折发生率为终点的对照研究来全面评估这些骨合成代谢药物在治疗骨质疏松症方面的潜力。

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