Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, 38163, United States.
Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38165, United States.
Curr Med Chem. 2021;28(8):1489-1507. doi: 10.2174/0929867327666200330142432.
CDATA[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.
骨质疏松症是一种由于骨重建失衡导致的骨量病理性丢失，在这种情况下，破骨细胞介导的骨吸收超过成骨细胞介导的骨形成，导致骨骼脆弱和骨折。抗吸收剂，如双膦酸盐和选择性雌激素受体调节剂，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骨素抑制剂，是目前治疗骨质疏松症的方法。尽管它们具有疗效，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。当前药物的序贯和联合使用，例如从合成代谢药物转换为抗吸收剂，可能是一种替代方法。此外，正在针对新兴靶点如组织蛋白酶 K 和 17β-HSD2 开发新型药物，这些药物可能具有更少的副作用。本文综述了骨质疏松症的分子机制、治疗骨质疏松症的现有药物以及新药物开发策略。
