Benzodiazepines linked with increased risk of hip fracture in Alzheimer’s disease

People with Alzheimer’s disease (AD) who are prescribed benzodiazepines have a 43% increased risk of hip fracture, a large Finnish study has found.

In a retrospective analysis of 46,373 AD patients, researchers found that one in five patients (or 21.1%) had initiated benzodiazepine use over the six-year study period (2005–2011).

In contrast, only 12.8% of the 92,746 age-matched control population were prescribed with benzodiazepines, drugs used to alleviate anxiety, agitation, and sleep disturbances.

The authors, who report their findings in the Journal of the American Medical Directors Association
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(online, 12 November 2016), found that although use of benzodiazepines increased the risk of hip fracture across the board, patients with AD were more likely (odds ratio 1.90) to end up in hospital for longer than four months after the fracture.

The researchers say this could be because people with AD often suffer from delirium, may require more demanding rehabilitation, or because of functional decline – loss of independence in self-care capabilities usually linked to deterioration in mobility– resulting from the use of benzodiazepines themselves.

The results suggest more caution should be used before prescribing them.

Commenting on the research, Clare Walton, research communications manager at the charity Alzheimer’s Society, says: “Benzodiazepines are known to increase the risk of falls in older people, but this is the first study to specifically examine its effects in people with Alzheimer’s disease. This is important because the drug can be used to treat the anxiety, agitation and insomnia that often comes hand in hand with dementia.”

She adds: “People with Alzheimer’s disease are already more susceptible to falls and are twice as likely to experience hip fracture. This study finds that benzodiazepine increases that risk even further, reinforcing our view that person-centred care approaches should always be considered first for people living with dementia.”

The data show that 2.5 hip fractures occurred per 100 person-years in AD patients during treatment with benzodiazepine and related drugs (such Z-drugs, a class of medicines which act in a similar way), whereas in patients who didn’t take benzodiazepine the incidence was 1.6 hip fractures per 100 person-years.

The researchers also point out that the risk of hip fracture was higher in patients with Alzheimer’s disease taking benzodiazepine within the first six months of treatment with figures showing that between one and six months of treatment the fracture risk was 2.61 times higher.

Considering the “rapidly increasing” number of people being diagnosed with AD globally, and the more frequent use of benzodiazepines in this population, the researchers conclude that it is important to reduce the risk of hip fracture, which can be a ‘devastating event’.

Lead author Laura Saarelainen, a PhD researcher at the school of pharmacy at the University of Eastern Finland, says that other treatment options should be considered. “Benzodiazepines should be used only in short-term or infrequent treatment of behavioural symptoms of Alzheimer’s disease,” she says.

“We know from previous studies that persons with Alzheimer’s experience more hip fractures than other older populations.”

Walton adds: “Importantly, the researchers found that people with both Alzheimer’s and hip fracture are more likely to stay in hospital for longer if they are taking benzodiazepines than if they are not — which is concerning given the negative impact that prolonged stays in hospital can have on the general health and well-being of people with dementia.”