The molecular mechanisms of action of bisphosphonates

被引：11
作者：
Thompson K. [1 ]
Rogers M.J. [1 ]
机构：
[1] Bone Research Group, Institute of Medical Sciences, Aberdeen AB25 2ZD, Foresterhill
来源：
Clinical Reviews in Bone and Mineral Metabolism | 2007年 / 5卷 / 3期
基金：
英国医学研究理事会;
关键词：
γδ T-cell; Bisphosphonate; Bone resorption; Farnesyl diphosphate; GTPase; Mevalonate; Osteoclast; Prenylation;
D O I：
10.1007/s12018-007-9004-0
中图分类号：
学科分类号：
摘要：
BPs can be grouped into two general classes according to their chemical structure and the molecular mechanism by which they inhibit osteoclast-mediated bone resorption. The simple BPs can be metabolically incorporated into non-hydrolysable analogues of ATP that accumulate intracellularly in osteoclasts, causing osteoclast cell death by apoptosis. By contrast, the more potent N-BPs inhibit FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids that are required for the prenylation of small GTPase signalling proteins necessary for osteoclast function. Inhibition of FPP synthase in cells other than osteoclasts also appears to account for the adverse effects of N-BPs in vivo (including the acute phase reaction) and for the anti-tumour effects of N-BPs in vitro. © 2007 Humana Press Inc.
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页码：130 / 144
页数：14
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