China Pharmaceutical University, Key Lab of State Natural Medicine, Department of Pharmaceutics , Nanjing 210009 , PR China +86 25 83271092; +86 25 83271317 ; +86 25 83271092; +86 25 83271317 ;
Expert Opin Ther Targets. 2014 Jul;18(7):817-31. doi: 10.1517/14728222.2014.912632. Epub 2014 Apr 25.
To date, osteoporosis still remains a major public health burden especially for the aging populations. Over the last few decades treatments for osteoporosis have largely focused on anti-resorptive agents represented by bisphosphonates and estrogen therapy that dominated the market. Unsatisfactory efficacy, non-specificity and long-term safety of current therapies necessitate the need for new targets effectively preventing and treating of osteoporosis.
This review expatiates on the mechanism of osteoporosis occurrence and bone remodeling cycle in detail. New targets of antiresorptive and anabolic agents based on the functions of osteoblasts and osteoclasts as well as associated signaling pathways are outlined.
Advanced understanding in the fields of bone remodeling, functions of osteoblasts, osteoclasts and osteocytes associated with osteoporosis occurrence offers the emerging bone-resorptive or bone-formative targets. Currently, molecules involving RANK-RANKL-OPG system and Wnt/β-catenin signaling pathway act as the most promising targets.
迄今为止,骨质疏松症仍然是一个主要的公共卫生负担,特别是对老龄化人口而言。在过去的几十年中,骨质疏松症的治疗主要集中在以双膦酸盐和雌激素治疗为代表的抗吸收剂上,这些药物主导了市场。目前治疗方法的疗效不理想、特异性差和长期安全性差,需要新的靶点来有效预防和治疗骨质疏松症。
本文详细阐述了骨质疏松症发生和骨重塑周期的机制。概述了基于成骨细胞和破骨细胞功能以及相关信号通路的抗吸收和合成代谢药物的新靶点。
在骨重塑、成骨细胞、破骨细胞和骨细胞功能领域的深入了解与骨质疏松症的发生有关,为新兴的骨吸收或骨形成靶点提供了依据。目前,涉及 RANK-RANKL-OPG 系统和 Wnt/β-catenin 信号通路的分子是最有前途的靶点。