Department of Medicine, Alexandra Hospital (Jurong Health), 378 Alexandra Road, Singapore 159964.
Rheumatology (Oxford). 2014 Jan;53(1):19-31. doi: 10.1093/rheumatology/ket236. Epub 2013 Jul 9.
Randomized controlled trials have demonstrated the efficacy of bisphosphonates (BP) in improving BMD and reducing fracture risk. Various safety issues that were not noted in clinical trials have, however, now emerged with post-marketing surveillance and increasing clinical experience. The risk of atypical femoral fracture could increase with long-term use of BP, although absolute risk is very small, particularly when balanced against benefits. A drug holiday should be considered after 5 years of treatment for patients at low risk of fracture, although there is no official recommendation regarding this to guide clinicians. Osteonecrosis of the jaw from low-dose BP used for osteoporosis is very rare, and mainly a complication with high-dose i.v. BP used in oncology. The risk of atrial fibrillation too is negligible, and a definite link cannot be established between BP and oesophageal cancer. BP should be avoided in patients with severe renal impairment and during pregnancy and lactation because of limited safety data. Further epidemiological and clinical data are required to establish safety of BP in long-term users (>5 years) and provide evidence-based management.
随机对照试验已经证明了双膦酸盐（BP）在改善骨密度和降低骨折风险方面的疗效。然而，随着上市后监测和临床经验的增加，现在出现了一些在临床试验中没有注意到的各种安全性问题。长期使用 BP 可能会增加非典型股骨骨折的风险，尽管绝对风险非常小，尤其是在权衡利弊之后。对于骨折风险低的患者，在治疗 5 年后应考虑停药，但目前尚无关于这方面的官方建议来指导临床医生。低剂量 BP 用于治疗骨质疏松症引起的颌骨坏死非常罕见，主要是与高剂量静脉 BP 用于肿瘤学治疗相关的并发症。房颤的风险也可以忽略不计，并且不能确定 BP 和食管癌之间存在必然联系。由于安全性数据有限，BP 应避免在严重肾功能不全、妊娠和哺乳期患者中使用。需要进一步的流行病学和临床数据来确定长期（>5 年）使用 BP 的安全性，并提供循证管理依据。
