Delmas Pierre D
Université de Lyon and INSERM Research Unit 831, Lyon, France.
J Clin Densitom. 2008 Apr-Jun;11(2):325-38. doi: 10.1016/j.jocd.2008.02.002. Epub 2008 Apr 2.
Osteoporosis affects millions of people worldwide, causing decreases in bone strength and a marked increase in fracture risk. Current therapies increase bone mineral density and reduce the risk of fractures, but dosing requirements are often considered inconvenient, and patient compliance with therapy is poor. This review will discuss recent discoveries in bone biology, which have demonstrated that the interaction of osteoprotegerin (OPG), receptor activator of nuclear factor--kappa B (RANK), and RANK ligand (RANKL) is critical for the regulation of bone remodeling. Collectively, these preclinical studies have shown that endogenous RANKL inhibition by OPG underlies the normal mechanism for maintaining the correct balance between bone resorption and bone formation. Multiple clinical trials are in progress to investigate the therapeutic potential of RANKL inhibition by denosumab, a fully human monoclonal anti-RANKL antibody, in the treatment of postmenopausal osteoporosis and other bone loss diseases. The results of these human trials will also be discussed.
骨质疏松症影响着全球数百万人，导致骨强度下降和骨折风险显著增加。目前的治疗方法可增加骨矿物质密度并降低骨折风险，但给药要求往往被认为不方便，患者对治疗的依从性较差。本综述将讨论骨生物学的最新发现，这些发现表明骨保护素（OPG）、核因子κB受体激活剂（RANK）和RANK配体（RANKL）之间的相互作用对于骨重塑的调节至关重要。总的来说，这些临床前研究表明，OPG对内源性RANKL的抑制作用是维持骨吸收和骨形成之间正确平衡的正常机制。多项临床试验正在进行中，以研究地诺单抗（一种完全人源化的抗RANKL单克隆抗体）抑制RANKL在治疗绝经后骨质疏松症和其他骨质流失疾病方面的治疗潜力。这些人体试验的结果也将进行讨论。
