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Anti-epileptic drugs associated with increased risk of fracture in older adults
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Most anti-epileptic drugs can be linked to an increased risk of non-traumatic fracture in individuals 50 years of age and older, according to a study recently published in Archives of Neurology.
The study is one of the first to associate individual anti-epileptic drugs with bone loss.
 Nathalie Jetté |
“Two population-based studies … confirmed that [anti-epileptic drug] use increases the rate of bone loss in adults older than 65 years but, aside from phenytoin and gabapentin, these studies were unable to examine the association of individual [anti-epileptic drugs] with bone loss,” the authors wrote.
A matched-cohort study
Nathalie Jetté, MD, Msc, and her colleagues used the Population Health Research Data Repository from Manitoba, Canada, to study the medical records of 15,792 individuals who experienced non-traumatic fractures of the wrist, hip and vertebra between April 1996 and March 2004. Each patient was matched with up to three controls – patients without a history of fracture – giving the study a total of 47,289 controls.
Individual anti-epileptic drugs studied included carbamazepine, clonazepam, ethosuximide, gabapentin, phenobarbital, phenytoin and valproic acid. Additional anti-epileptic drugs with fewer numbers of users were included together in a group labeled “other anti-epileptic drugs.”
Odds ratios for fracture from anti-epileptic drug exposure were adjusted for socio-demographic and comorbidity factors known to affect fracture risk.
Most drugs carry risk
The study found the highest likelihood of fractures to exist for patients taking phenytoin, followed by carbamazepine, “other anti-epileptic drugs,” phenobarbital, gabapentin and clonazepam.
The only anti-epileptic drug not associated with an increased likelihood of fracture was valproic acid.
The investigators reported that similar results were found when testing for the use of anti-epileptic drugs in monotherapy and in polytherapy. All anti-epileptic drugs used in monotherapy were associated with a “significantly increased risk” of fracture except valproic acid, phenobarbital and “other anti-epileptic drugs.”
Individuals in the polytherapy subgroups were found to have the greatest risk of fracture.
“Our study showed that most anti-epileptic drugs, except for valproic acid, are associated with an increased likelihood of non-traumatic fracture in individuals aged 50 years or older,” the authors wrote. “Future prospective studies of anti-epileptic drugs in newly-treated drug-naive patients are needed to better examine the individual effects of anti-epileptic drugs on bone health.”
The study was supported in part by an operating grant and New Investigator Awards from the Canadian Institutes of Health research and a research salary award from the Alberta Innovates Health Solutions.
Reference:
- Jetté N. Arch Neurol.2011. doi:10.1001/archneurol.2010.341
Disclosure: Jetté Dorfman has reported no relevant disclosures.
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