Nakamura Shinya, Tanaka Sakae
Graduate School of Medicine, Surgical Sciences, Orthopaedic Surgery, The University of Tokyo, Japan.
Clin Calcium. 2014 Jun;24(6):919-25.
Osteoporosis is a disorder of bone formation and resorption balance. Advances in our knowledge of the molecular mechanisms of bone formation and resorption led to promising therapeutic targets for osteoporosis. In the novel biological drugs, denosumab, a monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL) has been clinically applied by positive effect on bone mineral density, negative effect on bone resorption, preventive effect on fragility fractures and safety. Odanacatib, a cathepsin K inhibitor is drawing attention as an antiresorptive drug which has lower bone resorption potency than bisphosphoneate. On the other hand, BHQ-880, an anti-Dickkopf-1 (Dkk-1) antibody and romosozumab (AMG-785) , an anti-sclerostin antibody which activate Wnt/β-catenin signaling pathway are drawing attention as bone formation accelerators with no bone resorption acceleration. Clinical studies of these drugs are now ongoing and their clinical applications are expected.
骨质疏松症是一种骨形成与骨吸收平衡的紊乱疾病。我们对骨形成和骨吸收分子机制认识的进展,为骨质疏松症带来了有前景的治疗靶点。在新型生物药物中,地诺单抗,一种抗核因子κB受体活化剂配体(RANKL)的单克隆抗体,因其对骨密度的积极作用、对骨吸收的消极作用、对脆性骨折的预防作用及安全性,已在临床上得到应用。奥达卡替,一种组织蛋白酶K抑制剂,作为一种骨吸收抑制药物正受到关注,其骨吸收抑制效力低于双膦酸盐。另一方面,BHQ - 880,一种抗Dickkopf - 1(Dkk - 1)抗体,以及罗莫单抗(AMG - 785),一种激活Wnt/β - 连环蛋白信号通路的抗硬化蛋白抗体,作为不加速骨吸收的骨形成促进剂正受到关注。这些药物的临床研究正在进行中,其临床应用值得期待。