Calcium and vitamin D improve bone density in patients taking antiepileptic drugs

November 07, 2013

A recent prospective, randomized, placebo-controlled clinical trial reports that calcium and vitamin D supplementation improves bone density in a group of male veterans with epilepsy who were treated chronically with antiepileptic drugs (AEDs). The results published in Epilepsia, a journal of the International League Against Epilepsy (ILAE), suggest that risedronate, a bisphosphonate, may help to prevent new vertebral fractures when taken with calcium and vitamin D supplementation.

Many patients with epilepsy are required to take chronically an AED such as phenytoin, phenobarbital, carbamazepine, primidone, and valproate alone or in combination to control seizures. There is much medical evidence reporting that these AEDs may accelerate bone loss, increasing the risk of osteoporotic fractures. In fact, previous studies found that more than 50% of adults with epilepsy who use AEDs showed decreased bone mass in their hips or spine and the overall fracture risk of patients with epilepsy is considered to be larger than the normal population.

"Long-term use of AEDs is associated with loss of bone mass and increased risk of osteoporosis," explains Dr. Antonio Lazzari with the VA Boston Healthcare System in Massachusetts and lead author of the present study. "Our study is the first longitudinal trial of a bisphosphonate (risedronate), along with calcium and vitamin D supplementation, in preventing and treating bone loss in male veterans with epilepsy receiving AED therapy."

The antiepileptic drug and osteoporosis prevention trial (ADOPT) was a prospective two-year randomized, double-blind, placebo-controlled phase IV clinical trial of 80 male veterans with epilepsy who were treated with an AED for a minimum of two years. All participants received calcium and vitamin D supplements, and were randomized to risedronate or placebo. Subjects received total body, hip, and spine bone density assessments at baseline, one year and two years following their study enrollment.

Baseline characteristics of subjects were similar and 53 patients completed the two-year study. Significant improvement in bone density compared to baseline was observed in 69% and 70% of patients in the placebo and active drug groups, respectively. Patients taking risedronate displayed a significant increase in bone density at the lumbar spine, compared to subjects in the placebo group.

Dr. Lazzari concludes, "Our findings suggest calcium and vitamin D with or without risedronate improves bone density in epilepsy patients taking AEDs. However five new vertebral fractures were observed in the placebo group and none in the active medication group. Adding risedronate to the supplements appears to prevent new fractures in this group of veterans."

The authors caution that therapy with antiresorptive agents should be limited to five years to reduce side effects associated with long-term use of this group of drugs including osteonecrosis of the jaw and atypical femoral fractures. Researchers recommend future studies of efficacy and safety with the long-term use of bisphosphonates in patients with epilepsy.
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This study is published in Epilepsia. Media wishing to receive a PDF of this article may contact sciencenewsroom@wiley.com.

Full citation: "Prevention of Bone Loss and Vertebral Fractures in Patients with Chronic Epilepsy--Antiepileptic Drug and Osteoporosis Prevention Trial." Antonio A. Lazzari, Philip M. Dussault, Manisha Thakore-James, David Gagnon, Errol Baker, Samuel A. Davis and Antoun M. Houranieh. Epilepsia; Print Publication: November, 2013 (DOI: 10.1111/epi.12351).

URL:http://doi.wiley.com/10.1111/epi.12351

Author Contact: Media wishing to speak with Dr. Lazzari may contact antonio.lazzari@va.gov.

About the Journal

Epilepsia is the leading, most authoritative source for current clinical and research results on all aspects of epilepsy. As the journal of the International League Against Epilepsy, subscribers every month will review scientific evidence and clinical methodology in: clinical neurology, neurophysiology, molecular biology, neuroimaging, neurochemistry, neurosurgery, pharmacology, neuroepidemiology, and therapeutic trials. For more information, please visit http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1528-1167.

About the International League Against Epilepsy

The International League Against Epilepsy (ILAE) is the world's preeminent association of physicians and health professionals working toward a world where no person's life is limited by epilepsy. Since 1909 the ILAE has provided educational and research resources that are essential in understanding, diagnosing and treating persons with epilepsy. The ILAE supports health professionals, patients, and their care providers, governments, and the general public worldwide by advancing knowledge of epilepsy.

About Wiley

Wiley is a global provider of content-enabled solutions that improve outcomes in research, education, and professional practice. Our core businesses produce scientific, technical, medical, and scholarly journals, reference works, books, database services, and advertising; professional books, subscription products, certification and training services and online applications; and education content and services including integrated online teaching and learning resources for undergraduate and graduate students and lifelong learners.

Founded in 1807, John Wiley & Sons, Inc. (NYSE: JWa, JWb), has been a valued source of information and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations. Wiley and its acquired companies have published the works of more than 450 Nobel laureates in all categories: Literature, Economics, Physiology or Medicine, Physics, Chemistry, and Peace. Wiley's global headquarters are located in Hoboken, New Jersey, with operations in the U.S., Europe, Asia, Canada, and Australia. The Company's website can be accessed at http://www.wiley.com.

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