Benzodiazepines and Risk of Hip Fractures in Older People

Robert G. Cumming, David G. Le Conteur

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.