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除双膦酸盐和选择性雌激素受体调节剂之外的抗吸收药物用于绝经后骨质疏松症的管理

Antiresorptive drugs beyond bisphosphonates and selective oestrogen receptor modulators for the management of postmenopausal osteoporosis.

作者信息

Reginster J Y, Neuprez A, Beaudart C, Lecart M P, Sarlet N, Bernard D, Disteche S, Bruyere O

机构信息

Department of Public Health, Epidemiology and Health Economics, CHU Sart Tilman, University of Liège, 4020, Liège, Belgium,

出版信息

Drugs Aging. 2014 Jun;31(6):413-24. doi: 10.1007/s40266-014-0179-z.

Abstract

Osteoporotic fractures are a major cause of morbidity in the elderly population. Since postmenopausal osteoporosis is related to an increase in osteoclastic activity at the time of menopause, inhibitors of bone resorption have genuinely been considered an adequate strategy for prevention and treatment of osteoporosis. Bisphosphonates and selective oestrogen receptor modulators are widely prescribed to treat osteoporosis. However, other antiresorptive drugs have been developed for the management of osteoporosis, with the objective of providing a substantial reduction in osteoporotic fractures at all skeletal sites, combined with an acceptable long-term skeletal and systemic safety profile. Denosumab, a human monoclonal antibody to receptor activator for nuclear factor kappa B ligand, has shown efficacy against vertebral, nonvertebral and hip fractures. Its administration every 6 months as a subcutaneous formulation might significantly influence compliance and persistence to therapy. Additional results regarding long-term skeletal safety (i.e. osteonecrosis of the jaw and atypical diaphyseal femoral fracture) are needed. Odanacatib, a selective cathepsin K inhibitor, is a promising new approach to the inhibition of osteoclastic resorption, with the potential to uncouple bone formation from bone resorption. Results regarding its anti-fracture efficacy are expected in the coming months.

摘要

骨质疏松性骨折是老年人群发病的主要原因。由于绝经后骨质疏松与绝经时破骨细胞活性增加有关,骨吸收抑制剂已被真正视为预防和治疗骨质疏松的合适策略。双膦酸盐和选择性雌激素受体调节剂被广泛用于治疗骨质疏松症。然而,已开发出其他抗吸收药物来治疗骨质疏松症,目的是在所有骨骼部位大幅降低骨质疏松性骨折的发生率,并具有可接受的长期骨骼和全身安全性。地诺单抗是一种针对核因子κB受体活化因子配体的人单克隆抗体,已显示出对椎体、非椎体和髋部骨折的疗效。每6个月皮下注射一次的给药方式可能会显著影响治疗的依从性和持续性。还需要关于长期骨骼安全性的更多结果(即颌骨坏死和非典型股骨干骨折)。奥达卡替,一种选择性组织蛋白酶K抑制剂,是抑制破骨细胞吸收的一种有前景的新方法,有可能使骨形成与骨吸收解偶联。预计未来几个月将公布其抗骨折疗效的结果。

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