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骨质疏松症治疗的现有及新兴疗法。

Current and emerging therapies for the treatment of osteoporosis.

作者信息

Waalen Jill

机构信息

Department of Molecular and Experimental Medicine, The Scripps Research Institute, CA, USA.

出版信息

J Exp Pharmacol. 2010 Aug 27;2:121-34. doi: 10.2147/JEP.S7823. eCollection 2010.

Abstract

Osteoporosis represents a weakening of bone tissue due to an imbalance in the dynamic processes of bone formation and bone resorption that are continually ongoing within bone tissue. Most currently available osteoporosis therapies are antiresorptive agents. Over the past decade, bisphosphonates, notably alendronate and risedronate, have become the dominant agents with newer bisphosphonates such as ibandronate and zoledronic acid following a trend of less frequent dosing regimens. Synthetic estrogen receptor modulators (SERMs) continue to be developed as drugs that maintain the bone-protective effects of estrogen while avoiding its associated adverse side effects. Currently available agents of this class include raloxifene, the only SERM available in the United States (US), and lasofoxifene and bazedoxifene, available in Europe. Calcitonin, usually administered as a nasal spray, completes the list of currently approved antiresorptive agents, while parathyroid hormone analogs represent the only anabolic agents currently approved in both the US and Europe. Strontium ranelate is an additional agent available in Europe but not the US that has both anabolic and antiresorptive activity. New agents expected to further expand therapeutic options include denosumab, a monoclonal antibody inhibitor of the resorptive enzyme cathepsin K, which is in the final stages of Food and Drug Administration approval. Other agents in preclinical development include those targeting specific molecules of the Wnt/β-catenin pathway involved in stimulating bone formation by osteoblast cells. This review discusses the use of currently available agents as well as highlighting emerging agents expected to bring significant changes to the approach to osteoporosis therapy in the near future.

摘要

骨质疏松症是由于骨组织中持续进行的骨形成和骨吸收动态过程失衡而导致的骨组织弱化。目前大多数可用的骨质疏松症治疗方法是抗吸收剂。在过去十年中,双膦酸盐,尤其是阿仑膦酸盐和利塞膦酸盐,已成为主要药物,新型双膦酸盐如伊班膦酸盐和唑来膦酸则遵循给药方案频率降低的趋势。合成雌激素受体调节剂(SERM)继续作为一类药物进行研发,这类药物可维持雌激素的骨保护作用,同时避免其相关的不良副作用。目前该类可用药物包括雷洛昔芬(美国唯一可用的SERM)、拉索昔芬和巴多昔芬(在欧洲可用)。降钙素通常以鼻喷雾剂形式给药,是目前已批准的抗吸收剂之一,而甲状旁腺激素类似物是目前在美国和欧洲均已批准的唯一合成代谢药物。雷奈酸锶是一种在欧洲可用但在美国不可用的药物,它具有合成代谢和抗吸收活性。预计将进一步扩大治疗选择的新药包括地诺单抗,一种抗吸收酶组织蛋白酶K的单克隆抗体抑制剂,该药正处于美国食品药品监督管理局批准的最后阶段。其他处于临床前开发阶段的药物包括那些靶向参与刺激成骨细胞形成骨的Wnt/β-连环蛋白途径特定分子的药物。本综述讨论了目前可用药物的使用情况,并着重介绍了预计在不久的将来会给骨质疏松症治疗方法带来重大变化的新兴药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2422/4863293/5f0c42c8202b/jep-2-121Fig1.jpg

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