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合成代谢制剂与骨质量。

Anabolic agents and bone quality.

机构信息

Department of Orthopaedic Surgery, Boston University Medical Center, 720 Harrison Avenue, Suite 808, Boston, MA 02118, USA.

出版信息

Clin Orthop Relat Res. 2011 Aug;469(8):2215-24. doi: 10.1007/s11999-010-1722-9.

Abstract

BACKGROUND

The definition of bone quality is evolving particularly from the perspective of anabolic agents that can enhance not only bone mineral density but also bone microarchitecture, composition, morphology, amount of microdamage, and remodeling dynamics.

QUESTIONS/PURPOSES: This review summarizes the molecular pathways and physiologic effects of current and potential anabolic drugs.

METHODS

From a MEDLINE search (1996-2010), articles were identified by the search terms "bone quality" (1851 articles), "anabolic agent" (5044 articles), "PTH or parathyroid hormone" (32,229 articles), "strontium" or "strontium ranelate" (283 articles), "prostaglandin" (77,539 articles), and "statin" or "statins" (14,233 articles). The search strategy included combining each with the phrase "bone quality." Another more limited search aimed at finding more novel potential agents.

RESULTS

Parathyroid hormone is the only US Food and Drug Administration-approved bone anabolic agent in the United States and has been the most extensively studied in in vitro animal and human trials. Strontium ranelate is approved in Europe but has not undergone Food and Drug Administration trials in the United States. All the studies on prostaglandin agonists have used in vivo animal models and there are no human trials examining prostaglandin agonist effects. The advantages of statins include the long-established advantages and safety profile, but they are limited by their bioavailability in bone. Other potential pathways include proline-rich tyrosine kinase 2 (PYK2) and sclerostin (SOST) inhibition, among others.

CONCLUSIONS

The ongoing research to enhance the anabolic potential of current agents, identify new agents, and develop better delivery systems will greatly enhance the management of bone quality-related injuries and diseases in the future.

摘要

背景

骨质量的定义正在不断演变,特别是从合成代谢药物的角度来看,这些药物不仅可以提高骨矿物质密度,还可以改善骨微结构、组成、形态、微损伤程度和重塑动力学。

问题/目的:本文综述了目前和潜在的合成代谢药物的分子途径和生理作用。

方法

通过 MEDLINE 搜索(1996-2010 年),使用的检索词包括“骨质量”(1851 篇文章)、“合成代谢药物”(5044 篇文章)、“甲状旁腺激素或 PTH”(32229 篇文章)、“锶或雷奈酸锶”(283 篇文章)、“前列腺素”(77539 篇文章)和“他汀类药物或 statins”(14233 篇文章)。搜索策略包括将每个检索词与“骨质量”组合使用。另一个更有限的搜索旨在寻找更多新的潜在药物。

结果

甲状旁腺激素是美国食品和药物管理局批准的唯一一种骨合成代谢药物,已在体外动物和人体试验中得到广泛研究。雷奈酸锶在欧洲获得批准,但尚未在美国食品和药物管理局进行试验。所有关于前列腺素激动剂的研究都使用了体内动物模型,目前还没有研究前列腺素激动剂作用的人体试验。他汀类药物的优势包括其长期确立的优势和安全性,但它们受到其在骨骼中生物利用度的限制。其他潜在途径包括富含脯氨酸的酪氨酸激酶 2(PYK2)和骨硬化蛋白(SOST)抑制等。

结论

目前正在进行研究以增强现有药物的合成代谢潜力,发现新的药物,并开发更好的递送系统,这将极大地改善未来与骨质量相关的损伤和疾病的治疗。

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