Most antiepileptic 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.

Antiepileptic 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, antiepileptic 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. Dr. Nathalie Jetté from the Hotchkiss Brain Institute at the University of Calgary’s Faculty of Medicine and colleagues studied administrative healthcare data of 15,792 individuals who experienced non-traumatic fractures between April 1996 and March 2004. Each person was matched with up to three persons without a history of fracture, for a total of 47,289 controls.

The individual antiepileptic drugs studied included carbamazepine, clonazepam, ethosuximide, gabapentin, phenobarbital, phenytoin and valproic acid. Additional antiepileptic drugs (felbamate, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, primidone, topiramate and vigabatrin)  with fewer numbers of users were included together under “other antiepileptic drugs.”

The likelihood of fractures was highest for persons taking phenytoin followed by carbamazepine, others included phenobarbital, gabapentin and clonazepam. The only antiepileptic drug not associated with an increased likelihood of fracture, after adjusting for sociodemographic variables, homecare use and comorbidities, was valproic acid.

Similar results were found when testing for the use of antiepileptic 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 antiepileptic drugs.” The greatest risk of fracture was found in individuals in the polytherapy subgroups.

“In conclusion, our study showed that most antiepileptic 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 antiepileptic drugs in newly treated drug-naïve patients are needed to better examine the individual effects of anti-epileptic drugs on bone health.”

Source: University of Calgary Medical Center

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