Taking most anti-epileptic drugs raises the increased risk of breaking a bone in individuals 50 years of age and older, according to a new study.

The results show that the likelihood of fractures was highest for people taking phenytoin, which was followed by carbamazepine. Phenobarbital, gabapentin and clonazepam also ranked highly. The only anti-epileptic drug not associated with an increased likelihood of fracture was valproic acid, according to a statement released by the University of Calgary in Alberta.

Anti-epileptic drugs are considered a secondary risk factor for osteoporosis, according the researchers, 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, the researchers said.

While previous studies have 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, of the University of Calgary Foothills Hospital, 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 people who did have a fracture during that time, for a total of 47,289 controls.

The 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 researchers found similar results when testing for the use of anti-epileptic drugs in monotherapy (taking only one anti-epileptic drug) and in polytherapy (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 wrote. "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."

The study was published in the January issue of Archives of Neurology.