McClung Michael
Oregon Osteoporosis Center, Portland, Oregon 97213, USA.
Arthritis Res Ther. 2007;9 Suppl 1(Suppl 1):S3. doi: 10.1186/ar2167.
When the rate of bone resorption exceeds that of bone formation, destruction of bone tissue occurs, resulting in a fragile skeleton. The clinical consequences, namely osteoporosis and fragility fractures, are common and costly problems. Treatments that normalize the balance of bone turnover by inhibiting bone resorption preserve bone mass and reduce fracture risk. The discovery of receptor activator of nuclear factor-kappaB ligand (RANKL) as a pivotal regulator of osteoclast activity provides a new therapeutic target. Early studies have demonstrated that denosumab, an investigational, highly specific anti-RANKL antibody, rapidly and substantially reduces bone resorption. Pharmacokinetics of the antibody allow dosing by subcutaneous injection at an interval of 6 months. Inhibiting RANKL appears to be a promising new treatment for osteoporosis and related disorders. More information about the effectiveness of denosumab in reducing fracture risk, its tolerability and safety, and the response to discontinuing therapy will be provided by ongoing clinical studies.
当骨吸收速率超过骨形成速率时，骨组织会遭到破坏，导致骨骼脆弱。其临床后果，即骨质疏松症和脆性骨折，是常见且代价高昂的问题。通过抑制骨吸收使骨转换平衡恢复正常的治疗方法可维持骨量并降低骨折风险。核因子κB受体活化因子配体（RANKL）作为破骨细胞活性的关键调节因子的发现提供了一个新的治疗靶点。早期研究表明，地诺单抗，一种处于研究阶段的、高度特异性的抗RANKL抗体，能迅速且显著地减少骨吸收。该抗体的药代动力学特性允许每6个月皮下注射给药一次。抑制RANKL似乎是一种治疗骨质疏松症及相关疾病的有前景的新方法。正在进行的临床研究将提供更多关于地诺单抗在降低骨折风险方面的有效性、耐受性和安全性以及停药反应的信息。
