骨质疏松新药——地洛单抗研究进展

Research progress in Denosumab:A newmedicine for osteoporosis

研究表明,RANKL/RANK通路对人体骨骼健康具有重要意义。自身抗体与OPG中和的患者出现进展迅速的骨质疏松,这证实OPG在人体内的重要性。RANKL和OPG平衡以及这种平衡打破所带来的影响,尤其当这种平衡偏向RANKL时提示,抑制RANKL是治疗骨质疏松症一个有吸引力的方法。地诺单抗是首个用于抑制RANKL并可用于骨质疏松症和其他骨骼疾病治疗的药物。本文介绍了地诺单抗的早期研究及Ⅰ期、Ⅱ期、Ⅲ期研究内容及其相关结果,并对其治疗效果做了初步评价。描述在运用地诺单抗的过程中存在的问题,并评价了其安全性和耐受性。最后综述了地诺单抗相对于其他抗骨质疏松药物的优势以及尚存在的不确定问题。

It is demonstrated that RANKL/RANK pathway is important for human skeletal health. Rapidly progressive osteoporosis is found in a patient with autoantibodies that neutralizes OPG activity, confirming the importance of OPG in humans. The effect that thet balance is shifted in favor of RANKL indicates that inhibition of RANKL is an appealing strategy to treat osteoporosis. Denosumab is the first inhibitor of receptor activator of nuclear factor K-B ligand available for the treatment of osteoporosis and other bone diseases. This paper introduces results of earlier studies and phase 1, phase 2, and phase 3 study of denosumab and the preliminary evaluation of the treatment effect. It also points out the problems in using of denosumab, and evaluates its safety and tolerability. And finally it points out the advantages and drawbacks of denosumab comparing with other anti-osteoporosis drugs.