Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey.
Clin Ther. 2011 Nov;33(11):1547-59. doi: 10.1016/j.clinthera.2011.10.008.
Osteoporosis is a prevalent condition that may lead to increased risks for bone fracture and other morbidities and increased health care costs. Treatment modalities for osteoporosis aim to prevent further bone loss and to reduce the risk for fracture. Denosumab is a human monoclonal antibody developed for use in osteoporosis. It inhibits the receptor activator of nuclear factor κB ligand, a cytokine that mediates osteoclast-mediated bone resorption.
The intent of this article was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, efficacy, and tolerability of denosumab in the prevention and treatment of postmenopausal osteoporosis.
The MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations databases were searched for English-language reviews, abstracts, presentations, and clinical trials of denosumab in humans, published from 1995 through July 2011. Search terms included denosumab, osteoporosis, RANK ligand, and bone resorption. Available data were evaluated, and relevant clinical data were selected for inclusion.
Three Phase II and 4 Phase III studies that evaluated the efficacy of denosumab in postmenopausal women were identified. In a Phase III study, the percentage change from baseline in bone mineral density (BMD) was significantly greater with denosumab compared with placebo (+6.5% vs -0.6%, respectively; P < 0.0001). In another Phase III trial, the cumulative prevalence of vertebral fractures was significantly lower with denosumab compared with placebo (2.3% vs 7.2%; 95% CI, 0.26-0.41; P < 0.001). Denosumab treatment was associated with significantly greater changes in BMD at the total hip (+4.5% vs +3.4%; P < 0.0001) and distal radius (+1.1% vs +0.6%; P = 0.0001) compared with alendronate. Adverse events reported with the use of denosumab have included back pain (34.7%); pain in the extremities (11.7%); general musculoskeletal pain (7.6%); elevated cholesterol (7.2%); inflammation of the bladder (5.9%); and dermatologic conditions including dermatitis, eczema, and rashes (combined prevalence, 10.8%). Serious adverse events have included hypocalcemia (1.7%), pancreatitis (0.2%), and severe infection (0.2%). Several cases of osteonecrosis of the jaw have also been reported.
Based on the data from the available literature, denosumab is an efficacious and well-tolerated treatment for postmenopausal osteoporosis.
骨质疏松症是一种常见病症，可能会增加骨折风险和其他发病率，并增加医疗保健费用。骨质疏松症的治疗方法旨在防止进一步的骨质流失，并降低骨折风险。地舒单抗是一种用于治疗骨质疏松症的人源化单克隆抗体。它抑制核因子κB 配体受体激活剂，一种介导破骨细胞介导的骨吸收的细胞因子。
本文旨在综述地舒单抗在预防和治疗绝经后骨质疏松症中的临床药理学、药代动力学和药效学、疗效和耐受性。
检索了 1995 年至 2011 年 7 月期间在地舒单抗治疗人类骨质疏松症的英文评论、摘要、演示文稿和临床试验的 MEDLINE 和 MEDLINE In-Process & 其他非索引引文数据库。搜索词包括地舒单抗、骨质疏松症、RANK 配体和骨吸收。评估了现有数据，并选择了相关的临床数据进行纳入。
确定了三项评估地舒单抗在绝经后妇女中疗效的 II 期和四项 III 期研究。在一项 III 期研究中，与安慰剂相比，地舒单抗治疗的骨密度（BMD）从基线的变化百分比显著更大（分别为+6.5%对-0.6%；P<0.0001）。在另一项 III 期试验中，与安慰剂相比，地舒单抗治疗的椎体骨折累积发生率显著降低（2.3%对 7.2%；95%CI，0.26-0.41；P<0.001）。与阿仑膦酸钠相比，地舒单抗治疗的总髋部（+4.5%对+3.4%；P<0.0001）和桡骨远端（+1.1%对+0.6%；P=0.0001）的 BMD 变化显著更大。使用地舒单抗报告的不良反应包括背痛（34.7%）、四肢疼痛（11.7%）、一般肌肉骨骼疼痛（7.6%）、胆固醇升高（7.2%）、膀胱炎（5.9%）和皮肤病况，包括皮炎、湿疹和皮疹（总患病率为 10.8%）。严重不良事件包括低钙血症（1.7%）、胰腺炎（0.2%）和严重感染（0.2%）。也有几例下颌骨坏死的报告。
根据现有文献数据，地舒单抗是一种治疗绝经后骨质疏松症有效且耐受性良好的药物。
