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Anti-epileptic drugs associated with increased risk of fracture in older adults

The JAMA Network Journals

Most anti-epileptic drugs are associated with an increased risk of non-traumatic fracture in individuals 50 years of age and older, according to a report in the January issue of Archives of Neurology, one of the JAMA/Archives journals.

Anti-epileptic drugs are considered a secondary risk factor for osteoporosis, according to background information in the article, because epilepsy is highly prevalent in older adults, a population already at risk for osteoporosis. Additionally, anti-epileptic drugs are associated with greater bone density reduction in post-menopausal women with epilepsy.

While there have been studies that examined the link between anti-epileptic drugs and bone density loss in adults older than 65, little evidence exists for the association of individual anti-epileptic drugs with bone loss. Nathalie Jetté, M.D., M.Sc., of the University of Calgary, Foothills Hospital, Alberta, Canada, and colleagues studied medical records of 15,792 individuals who experienced non-traumatic fractures between April 1996 and March 2004. Each person was matched with up to three controls, persons without a history of fracture, for a total of 47,289 controls.

The 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 under "other anti-epileptic drugs."

The likelihood of fractures was highest for persons taking phenytoin followed by carbamazepine, other, phenobarbital, gabapentin and clonazepam. The only anti-epileptic drug not associated with an increased likelihood of fracture was valproic acid.

Similar results were found when testing for the use of anti-epileptic drugs in monotherapy (individuals taking only one anti-epileptic drug) and in polytherapy (individuals taking more than one anti-epileptic drug). All anti-epileptic drugs used in monotherapy were associated with a significantly increased risk of fracture except for valproic acid, phenobarbital and "other anti-epileptic drugs." The greatest risk of fracture was found in individuals in the polytherapy subgroups.

"In conclusion, 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 write. "Future prospective studies of anti-epileptic drugs in newly treated drug-naïve patients are needed to better examine the individual effects of anti-epileptic drugs on bone health."

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(Arch Neurol. 2011;68[1]:107-112. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This 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. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

To contact Nathalie Jetté, M.D., M.Sc., call Marta Cyperling at 403-210-3835 or e-mail marta.cyperling@ucalgary.ca.

For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org.

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