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© 2005 American Academy of Neurology Effect of antiepileptic medication on bone mineral measuresFrom The University of Melbourne (Drs. Petty, O'Brien, Wark, L.M. Paton), Department of Medicine, Bone and Mineral Service (Dr. Wark, L.M. Paton) and Department of Neurology (Drs. Petty, O'Brien), The Royal Melbourne Hospital, Victoria, Australia; Institute of Bone and Joint Research (Dr. Sambrook, J. Makovey), Royal North Shore Hospital, NSW, Australia; Epilepsy Research Centre (Dr. Berkovic), The University of Melbourne, Austin Health, Victoria, Australia; Department of Genetic Epidemiology (Dr. Erbas), The University of Melbourne, Victoria, Australia. Address correspondence and reprint requests to Professor John Wark, The Department of Medicine, The Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia; e-mail: jdwark{at}unimelb.edu.au Objective: Long-term antiepileptic drug (AED) use has been associated with bone disease, but many previous studies have been limited by inadequate control subjects. We used a cotwin affected sib-pair model to investigate this issue. Methods: The authors studied 31 female twin (15 monozygous and 16 dizygous) and four sibling pairs (<3 years age difference) aged 21 to 75 years, in which one member had >12 months of AED treatment. Areal bone mineral density (ABMD, g/cm2) was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN), and total forearm (FA). Three primary a priori defined subgroups were analyzed: a) use for >2 years, b) use of enzyme-inducing AEDs, or c) age older than 40 years. Results: For all pairs (n = 35), there were no significant within-pair differences in any ABMD measure. However, in Subgroup a (n = 27), there was a within-pair difference at the FA (0.513 vs 0.534, –3.9%, p = 0.016). In Subgroup b (n = 29), there was also a within-pair difference at the FA for AED user vs nonuser (0.508 vs 0.529, –3.8%, p = 0.010). In Subgroup c (n = 15), there were within-pair differences at the FA (0.492 vs 0.524, –6.1%, p = 0.017) and the LS (0.884 vs 0.980, –9.8%, p = 0.036). Conclusions: Patients using AEDs for >2 years, in particular those taking enzyme-inducing AEDs and those older than 40 years, have significantly lower bone mineral density at clinically relevant fracture risk sites.
Commentary, see page 1343 Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 8 issue to find the title link for this article. The AED bone project is funded by the Epilepsy Association, Eli Lilly, and The Victor Hurley Grants-in-Aid at The Royal Melbourne Hospital. Dr. Petty is funded by a NHMRC Postgraduate Research Scholarship and the Epilepsy Association. Disclosure: The authors report no conflicts of interest. Received November 16, 2004. Accepted in final form July 18, 2005.
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