Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy.
Expert Opin Ther Targets. 2020 Feb;24(2):115-130. doi: 10.1080/14728222.2020.1726889. Epub 2020 Feb 12.
: Osteoporosis is a chronic, skeletal disorder characterized by compromised bone strength and increased fracture risk; it affects 50% of women and 20% of men. In the past two decades, there have been substantial improvements in the pharmacotherapy of osteoporosis which have yielded potent inhibitors of bone resorption or stimulators of bone formation.: This review discusses newly identified targets and pathways and conceptual approaches to the prevention of multiple age-related disorders. Furthermore, it summarizes existing therapeutic strategies for osteoporosis.: Our enhanced understanding of bone biology and the reciprocal interactions between bone and other tissues have allowed the identification of new targets that may facilitate the development of novel drugs. These drugs will hopefully achieve the uncoupling of bone formation from resorption and possibly exert a dual anabolic and antiresorptive effect on bone. Alas, limitations regarding adherence, efficacy on nonvertebral fracture prevention and the long-term adverse events still exist for currently available therapeutics. Moreover, the efficacy of most agents is limited by the tight coupling of osteoblasts and osteoclasts; hence the reduction of bone resorption invariably reduces bone formation, and vice versa. This field is very much 'a work in progress.'
骨质疏松症是一种慢性骨骼疾病，其特征是骨强度受损和骨折风险增加；它影响 50%的女性和 20%的男性。在过去的二十年中，骨质疏松症的药物治疗取得了实质性的进展，产生了强效的骨吸收抑制剂或骨形成刺激剂。本文讨论了新发现的靶点和途径以及预防多种与年龄相关疾病的概念方法。此外，还总结了现有的骨质疏松症治疗策略。我们对骨骼生物学和骨骼与其他组织之间的相互作用的理解的提高，使得能够确定新的靶点，这些靶点可能有助于开发新的药物。这些药物有望实现骨形成与骨吸收的解偶联，并可能对骨骼产生双重的促合成代谢和抗吸收作用。遗憾的是，目前可用的治疗方法在依从性、非椎体骨折预防的疗效和长期不良事件方面仍存在局限性。此外，大多数药物的疗效受到成骨细胞和破骨细胞紧密偶联的限制；因此，骨吸收的减少不可避免地会减少骨形成，反之亦然。这个领域还在不断发展。
