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预防骨质疏松症的新靶点——从代谢性骨病研究中获得的经验教训。

Novel targets for the prevention of osteoporosis - lessons learned from studies of metabolic bone disorders.

作者信息

Henriksen Kim, Thudium Christian Schneider, Christiansen Claus, Karsdal Morten Asser

机构信息

a Department of Musculoskeletal Diseases, Nordic Bioscience Biomarkers and Research , Herlev Hovedgade 207, DK-2730 Herlev, Denmark

出版信息

Expert Opin Ther Targets. 2015;19(11):1575-84. doi: 10.1517/14728222.2015.1045415. Epub 2015 May 10.

Abstract

INTRODUCTION

Osteoporosis is a major health care problem, and whereas efficacious treatments for vertebral fracture reduction are available for osteoporosis patients, these therapies are still limited with respect to capacity for restoration of bone loss, as well as efficacy on non-vertebral fractures, such as hip fractures, which are the source of morbidity and mortality.

AREAS COVERED

Studies of rare bone diseases in humans, such as osteopetrosis, sclerosteosis, pycnodysostosis and more, have shed light on a series of drug targets in bone that have the potential to result in therapies for osteoporosis with novel mechanisms of action, and the potential to improve the standard of care substantially. We focus on how they are separated from classic treatments for osteoporosis, in terms of novel modes of action, additional beneficial effects on bone turnover and importantly also safety. We focus on the status of anti-sclerostin antibodies, novel parathyroid hormone-related protein analogs, inhibitors of cathepsin K and ClC-7 in osteoclasts, all of which are currently in development.

EXPERT OPINION

There is a good possibility that the treatment of osteoporosis will be greatly improved within the coming years; however, with numerous effective and safe drugs already available careful attention to the safety of these novel candidates is crucial.

摘要

引言

骨质疏松症是一个重大的医疗保健问题,虽然有有效的治疗方法可减少骨质疏松症患者的椎体骨折,但这些疗法在恢复骨质流失的能力以及对非椎体骨折(如髋部骨折,这是发病和死亡的根源)的疗效方面仍然有限。

涵盖领域

对人类罕见骨病的研究,如骨硬化症、骨肥厚症、致密性骨发育不全等,揭示了一系列骨中的药物靶点,这些靶点有可能带来具有新作用机制的骨质疏松症治疗方法,并有可能大幅提高护理标准。我们关注它们与骨质疏松症经典治疗方法的区别,包括新的作用模式、对骨转换的额外有益影响以及重要的安全性。我们关注抗硬化蛋白抗体、新型甲状旁腺激素相关蛋白类似物、组织蛋白酶K抑制剂和破骨细胞中的ClC - 7的研发现状,所有这些目前都在开发中。

专家意见

未来几年骨质疏松症的治疗很有可能会得到极大改善;然而,鉴于已有众多有效且安全的药物,谨慎关注这些新型候选药物的安全性至关重要。

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