骨质疏松治疗药物的研究进展

Research progress of drugs for osteoporosis treatment

骨质疏松是一种以骨量减少和骨组织微结构破坏为特征,并能导致骨脆性增加和易于骨折的全身性疾病.目前治疗该病的主要目的是预防骨折的发生,但仍没有特效药.在治疗骨质疏松的3类药物中,骨吸收抑制剂是当前的主要药物,它通过抑制骨的重吸收来提高骨密度;骨形成促进剂可以直接刺激骨形成,并且有重建骨组织的效应;骨矿化物是防治骨质疏松的基础药物,包括钙剂和维生素D.然而,随着科学研究的不断深入,出现了一些新的治疗理念和策略,靶向治疗成为未来药物的发展趋势.当前以RANKL信号通路和Wnt信号通路的研究为依据的各种骨生长因子制剂(如denosumab,sclerostin antibody等)逐渐被开发,疗效也较好.另外,BMP信号通路作为骨生长的重要调节通路,其刺激骨形成的作用十分突出,且在该通路的调节蛋白中存在较多潜在靶点,如Smurf1,CKIP-1等.这在靶向治疗骨质疏松的新药研发领域值得深入探讨.

Osteoporosis is a systemic disease characterized by bone loss and bone tissue micro-structural damage, leading to bone fragility and an increased risk of bone fractures. The main purpose of osteoporosis treatment is to prevent the occurrence of fracture, but current drugs rarely achieve this goal with specific and notable therapeutic effects. There are mainly three types of drug used for osteoporosis treatment： bone resorption inhibitors is the largest class, it can increase bone mineral density through inhibiting bone resorption; bone anabolic agents can stimulate bone formation directly and rebuild bone tissue; bone mineralizers is the basic medicine of preventing and curing osteoporosis, and it includes calcium and vitamin D. However, with the development of scientific research, some new treatment concepts and strategies are proposed, and targeted therapy has become the development tendency of drugs in the future. Currently, various bone growth factor preparations （such as Denosumab, Sclerostin antibody, etc） have been gradually developed, which are based on studies of RANKL signaling pathway and Wnt signaling pathway, and their effect is better. In addition, as an important regulatory pathway, BMP signaling pathway plays a prominent role in stimulating bone formation. Regulatory proteins of this pathway have many potential targets, such as Smurfl, CKIP-1. It is worth discussing in the research and development of new drugs for osteoporosis treatment.