Osteoporosis: Mechanism, Molecular Target and Current Status on Drug Development.

Osteoporosis: Mechanism, Molecular Target and Current Status on Drug Development.
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骨质疏松:机制、分子靶点及药物开发现状。

DOI:
10.2174/0929867327666200330142432
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发表时间:
2021
影响因子:
4.1
通讯作者:
Li W
Li W
中科院分区:
医学3区
文献类型:
--
作者:
Li H;Xiao Z;Quarles LD;Li W

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骨质疏松症是由于破骨细胞介导的骨吸收超过成骨细胞介导的骨形成,导致骨骼脆性和骨折的骨重建失衡导致的骨量的病理性丢失。抗吸收药物,如双膦酸盐和SERM,以及刺激骨形成的合成代谢药物,包括甲状旁腺素类似物和硬化素抑制剂,是目前治疗骨质疏松症的方法。尽管它们有效,但严重的副作用和效力丧失可能会限制单一药物的长期使用。当前药物的顺序和联合使用,例如从合成代谢药物转换为抗吸收药物,可能提供一种替代方法。此外,正在开发针对新出现的新靶点的新药,如组织蛋白酶K和17β-HSD2,它们可能具有较少的副作用。本文将对骨质疏松症的分子机制、目前治疗骨质疏松症的药物以及新药开发策略进行综述。
Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents, such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone formation, including PTH analogues and sclerostin inhibitors, are current treatments for osteoporosis. Despite their efficacy, severe side effects and loss of potency may limit the long term usage of a single drug. Sequential and combinational use of current drugs, such as switching from an anabolic to an anti-resorptive agent, may provide an alternative approach. Moreover, there are novel drugs being developed against emerging new targets such as Cathepsin K and 17β-HSD2 that may have less side effects. This review will summarize the molecular mechanisms of osteoporosis, current drugs for osteoporosis treatment, and new drug development strategies.
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