Kherani Raheem B, Papaioannou Alexandra, Adachi Jonathan D
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Drug Saf. 2002;25(11):781-90. doi: 10.2165/00002018-200225110-00003.
Osteoporosis in postmenopausal women is a growing health concern for society. Bisphosphonates have become the mainstay of prevention and treatment with the mounting evidence of their efficacy over the past two decades. This review article examines the use of the etidronate, alendronate and risedronate. The pivotal trials are reviewed for long-term tolerability, evidence regarding histological safety and gastrointestinal tolerance. Etidronate, alendronate and risedronate have also been examined in meta-analyses, which reviewed methodologically sound trials. Length of treatment, adverse events and medication discontinuation and patients lost to follow-up were evaluated. Etidronate trials and the recent meta-analysis support the safe clinical use of cyclical etidronate with no signs of osteomalacia or other skeletal pathology over 2 to 3 years. In addition to increased bone mineral density (BMD) and vertebral fracture risk reduction, patients tolerated cyclical etidronate well up to 4 years in randomised studies. Non-randomised data has shown safety up to 7 years with clinical and bone biopsy data. Alendronate studies demonstrated similar overall adverse event rates, study discontinuation rates and loss to follow-up rates between placebo and treatment arms, in addition to consistent improvements in BMD, vertebral and non-vertebral fracture risk reductions over 3 to 4 years. Histological safety has been demonstrated up to 3 years. Longer-term therapy in non-randomised trials up to 7 years showed similar clinical safety between alendronate and placebo. Risedronate trials and the meta-analysis also showed similar adverse event profiles between placebo and treatment arms, as well as improvements in BMD, vertebral and non-vertebral fracture risk reductions up to 3 years. Rates of discontinuation due to gastrointestinal events were similar between groups. Histological safety has also been demonstrated for risedronate up to 3 years. Each of these bisphosphonates have been shown to have comparable safety with placebo up to 3 to 4 years, with the most rigourous trials carried out for alendronate and risedronate. Long-term comparative studies are awaited.
绝经后女性的骨质疏松症日益引起社会对健康问题的关注。在过去二十年里，随着双膦酸盐疗效证据的不断增加，它们已成为预防和治疗的主要手段。这篇综述文章探讨了依替膦酸、阿仑膦酸和利塞膦酸的使用情况。对关键试验进行了回顾，以评估其长期耐受性、组织学安全性和胃肠道耐受性方面的证据。依替膦酸、阿仑膦酸和利塞膦酸也在荟萃分析中得到了研究，这些分析回顾了方法学合理的试验。评估了治疗时长、不良事件、药物停用情况以及失访患者。依替膦酸试验和近期的荟萃分析支持了周期性使用依替膦酸在临床中的安全性，在2至3年期间未出现骨软化症或其他骨骼病变的迹象。除了骨密度（BMD）增加和椎体骨折风险降低外，在随机研究中，患者对周期性使用依替膦酸的耐受性良好，长达4年。非随机数据显示，根据临床和骨活检数据，其安全性可达7年。阿仑膦酸研究表明，安慰剂组和治疗组之间的总体不良事件发生率、研究中断率和失访率相似，此外，在3至4年期间，骨密度持续改善，椎体和非椎体骨折风险降低。已证明其组织学安全性可达3年。在非随机试验中长达7年的长期治疗显示，阿仑膦酸和安慰剂之间的临床安全性相似。利塞膦酸试验和荟萃分析还显示，安慰剂组和治疗组之间的不良事件情况相似，以及在长达3年的时间里骨密度得到改善且椎体和非椎体骨折风险降低。因胃肠道事件导致的停药率在各组之间相似。利塞膦酸的组织学安全性也已证明可达3年。在长达3至4年的时间里，这些双膦酸盐中的每一种都已显示出与安慰剂具有相当的安全性，其中对阿仑膦酸和利塞膦酸进行了最严格的试验。期待进行长期比较研究。
