Cumming Robert G, Le Couteur David G
School of Public Health and Centre for Education and Research on Ageing, University of Sydney, Sydney, New South Wales, Australia.
CNS Drugs. 2003;17(11):825-37. doi: 10.2165/00023210-200317110-00004.
A hip fracture epidemic is occurring in developed countries in association with population aging. The increasing number of people with a hip fracture has major implications for clinicians and health service managers. More importantly, a hip fracture is a devastating event in the life of an older person, as it often leads to loss of independence and death. Identification of risk factors for hip fracture is an essential first step towards prevention. The use of psychotropic medications is an established risk factor for hip fracture. The purpose of this article is to systematically review epidemiological studies of the relationship between use of benzodiazepines and risk of hip fracture and, then, to see how the findings of these studies fit with what is known about the pharmacology of benzodiazepines. Eleven primary epidemiological studies were identified. The results of these studies were not consistent; however, the inconsistency appeared to be almost entirely explained by research design. The studies that did not show an association between increased hip fracture risk and benzodiazepine use were nearly all hospital-based case-control studies, a type of study that often lacks validity because of the difficulty of finding an appropriate control group. After excluding the hospital-based case-control studies, all but one of the remaining seven studies found that use of benzodiazepines was associated with an increased risk of hip fracture that varied between 50% and 110%. The only higher quality study that did not find an association between benzodiazepine use and hip fracture was also the only study conducted entirely in nursing homes. There was no evidence that the risk of hip fracture differed between short- and long-acting benzodiazepines. People using higher doses of benzodiazepines and those who had recently started using benzodiazepines were at the highest risk of hip fracture. In very old people, there was some preliminary evidence that benzodiazepines that undergo oxidation in the liver may be associated with a higher risk of hip fracture than other benzodiazepines. The epidemiological evidence strongly suggests that the use of benzodiazepines by older people increases their risk of hip fracture by at least 50%. The benefits of benzodiazepines for older people are unclear. Given the high morbidity and mortality of hip fracture, it can be concluded that older people should rarely be prescribed benzodiazepines and that many older people already taking these drugs should have them withdrawn under appropriate supervision.
随着人口老龄化,发达国家正面临髋部骨折的流行。髋部骨折患者数量的增加对临床医生和医疗服务管理者具有重大影响。更重要的是,髋部骨折对老年人的生活来说是一场灾难性事件,因为它常常导致失去独立生活能力甚至死亡。识别髋部骨折的风险因素是预防工作至关重要的第一步。使用精神药物是已确定的髋部骨折风险因素。本文的目的是系统回顾关于苯二氮䓬类药物使用与髋部骨折风险之间关系的流行病学研究,然后考察这些研究结果与已知的苯二氮䓬类药物药理学知识如何契合。共识别出11项主要的流行病学研究。这些研究结果并不一致;然而,这种不一致似乎几乎完全可以由研究设计来解释。那些未显示髋部骨折风险增加与使用苯二氮䓬类药物之间存在关联的研究几乎都是基于医院的病例对照研究,这类研究往往缺乏效度,因为难以找到合适的对照组。排除基于医院的病例对照研究后,其余7项研究中除一项外,均发现使用苯二氮䓬类药物与髋部骨折风险增加相关,风险增幅在50%至110%之间。唯一一项未发现苯二氮䓬类药物使用与髋部骨折之间存在关联的高质量研究也是唯一一项完全在养老院开展的研究。没有证据表明短效和长效苯二氮䓬类药物在髋部骨折风险上存在差异。使用高剂量苯二氮䓬类药物的人群以及最近开始使用苯二氮䓬类药物的人群髋部骨折风险最高。在高龄老人中,有一些初步证据表明在肝脏中发生氧化代谢的苯二氮䓬类药物可能比其他苯二氮䓬类药物与更高的髋部骨折风险相关。流行病学证据有力地表明,老年人使用苯二氮䓬类药物会使他们的髋部骨折风险至少增加50%。苯二氮䓬类药物对老年人的益处尚不明确。鉴于髋部骨折的高发病率和高死亡率,可以得出结论,老年人应极少被开具苯二氮䓬类药物,并且许多已经在服用这些药物的老年人应在适当监督下停药。