Hirao Makoto, Hashimoto Jun
Department of Orthopaedics, National Hospital Organization, Osaka Minami Medical Center, Japan.
Clin Calcium. 2011 Aug;21(8):1231-8.
Denosumab directly targets osteoclastgenesis by its specific action on the RANKL pathway, while bisphosphonate acts as antiresorptive agents mainly by their suppression on function of osteoclasts. The previous clinical trials showed that denosumab resulted in a quicker decrease in markers of bone resorption than bisphosphonate, that denosumab has beneficial effect against the prevention of fracture in postmenopausal women and bone erosion in patients with rheumatoid arthritis and that recombinant osteoprotegerin provided the therapeutic efficacy in two adult siblings with juvenile Paget's disease. Taken together, it is strongly expected that denosumab would be developed to be one of potent therapeutic agents for Paget's disease of bone which is characterized with the accerelated bone resorpton by osteoclasts as the primitive pathological condition.
地诺单抗通过对RANKL途径的特异性作用直接靶向破骨细胞生成,而双膦酸盐主要通过抑制破骨细胞功能发挥抗吸收剂的作用。先前的临床试验表明,地诺单抗导致骨吸收标志物的下降比双膦酸盐更快,地诺单抗对预防绝经后妇女骨折和类风湿性关节炎患者的骨侵蚀有有益作用,并且重组骨保护素对两名患有青少年佩吉特病的成年兄弟姐妹具有治疗效果。综上所述,人们强烈期望地诺单抗能够被开发成为治疗骨佩吉特病的有效治疗药物之一,该病的主要病理状况是破骨细胞加速骨吸收。