Molecular biology of bone remodeling: implications for new therapeutic targets for osteoporosis.
Molecular biology of bone remodeling: implications for new therapeutic targets for osteoporosis.
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DOI：
10.1016/j.maturitas.2010.01.002
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发表时间：
2010-04
期刊：
影响因子：
4.9
通讯作者：
Sai, A. J.
中科院分区：
文献类型：
--
作者：
Gallagher, J. Chris;Sai, A. J.
骨质疏松症是55岁以上成年人的主要公共卫生问题，耗资数十亿欧元/美元。在过去的20年里，抗骨吸收药物是治疗骨质疏松症的首选药物，大多数是从双膦酸盐分子中提取的。在过去的7年里，分子生物学和遗传学的显著进步导致了对骨重塑周期的详细了解，并因此出现了新的治疗靶点。这些新化合物根据其在骨重塑周期中的作用有不同的作用模式。一个重要的发现是RANKL（受体激活因子核κ B配体）的重要作用，由成骨细胞分泌，负责刺激破骨细胞骨吸收。这导致了一种阻断其作用的强效单克隆抗体的发展。这种药物将很快成为治疗骨质疏松症的新方法。吸收中的其他分子靶点已经确定，一些特异性拮抗剂是潜在的治疗方法。然而，一种新的抗骨吸收药物的一个重要限制因素是将其推向市场的成本，因为骨折试验的成本很高。虽然抗骨吸收药物一直是骨质疏松症治疗的支柱，但它们不能重建骨结构，合成代谢药物的开发是必要的。这些可能是从对LRP/Wnt信号通路的理解演变而来的。一种针对硬化蛋白的抗体已经在动物研究中显示出希望，不要忘记甲状旁腺激素，它是第一个临床有用的骨质疏松症合成代谢治疗药物。
Osteoporosis is a major public health problem for adults over age 55 years costing billions of Euros/Dollars. Over the last 20 years antiresorptive drugs were the treatment of choice for osteoporosis and most were derived from the Bisphosphonate molecule. In the last 7 years remarkable advances in molecular biology and genetics have led to a detailed understanding of the bone remodeling cycle and as a result new therapeutic targets for treatment emerged. These new compounds have different modes of action depending on their role in the bone remodeling cycle. A major discovery was the important role of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) secreted by osteoblasts and responsible for stimulating osteoclastic bone resorption. This led to development of a potent monoclonal antibody that blocks its action. This drug should be available soon as a new treatment for osteoporosis. Other molecular targets in resorption have been identified and several specific antagonists are potential treatments. However, a significant limiting factor for a new anti resorptive drug is the cost of bringing it to the market because of the huge costs of a fracture trial. Although anti resorptive agents have been the backbone of osteoporosis treatment they do not rebuild bone architecture and development of anabolic agents are needed. These are likely to evolve from an understanding of the LRP/Wnt signaling pathway. Already an antibody against sclerostin has shown promise in animal studies, and not to forget parathyroid hormone which was the first clinically useful anabolic treatment for osteoporosis.
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影响因子：
4.1
作者：
Jilka, Robert L.;O'Brien, Charles A.;Ali, A. Afshan;Roberson, Paula K.;Weinstein, Robert S.;Manolagas, Stavros C.
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Manolagas, Stavros C.
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影响因子：
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