Burkiewicz Jill S, Scarpace Sarah L, Bruce Susan P
Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, IL 60515, USA.
Ann Pharmacother. 2009 Sep;43(9):1445-55. doi: 10.1345/aph.1M102. Epub 2009 Jul 21.
To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma.
Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966-July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-kappaB ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer.
All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone.
In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization.
Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.
综述地诺单抗在骨质疏松症、乳腺癌、前列腺癌和多发性骨髓瘤中的药理学、药代动力学、药效学、安全性、疗效及应用。
通过MEDLINE和国际药学文摘（1966年 - 2009年7月）检索研究和摘要。关键检索词包括地诺单抗、AMG - 162和核因子κB受体激活剂配体系统。以摘要形式提供的信息从主要的肿瘤学和骨代谢会议中获取。其他数据从制造商处获得。
纳入所有可用的人体研究，但不包括类风湿关节炎和骨巨细胞瘤的研究。
在骨质疏松症患者中，地诺单抗显著降低骨吸收和骨折发生率。地诺单抗预防和治疗骨质疏松症的研究表明，骨矿物质密度显著增加，骨转换标志物降低。地诺单抗与安慰剂治疗骨质疏松症的研究表明，椎体、髋部和非椎体骨折减少。在肿瘤学方面，接受乳腺癌和前列腺癌内分泌治疗的患者临床试验取得阳性结果，表明骨丢失和骨相关事件减少。在地诺单抗在肿瘤学环境中降低骨转换标志物方面，其效果似乎至少与静脉注射双膦酸盐一样有效。骨质疏松症患者最常见的不良反应是关节痛、鼻咽炎、背痛和头痛。癌症患者最常见的不良反应是感染、肢体疼痛、关节痛、骨痛、疲劳和疼痛。严重不良反应包括需要住院治疗的感染。
地诺单抗在骨质疏松症、乳腺癌和前列腺癌患者中已证明有效且安全。需要更多的临床试验数据来更全面地确定地诺单抗在治疗骨质疏松症和肿瘤性疾病方面的有效性及其成本效益和长期安全性。
