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From the Center for Chronic Disease Outcomes Research (K.E.E.), VA Medical Center, Minneapolis; Department of Medicine and Division of Epidemiology & Community Health (K.E.E.) and Department of Neurology (T.S.W.), University of Minnesota, Minneapolis; Minnesota Comprehensive Epilepsy Program (T.S.W.), Minneapolis; Research Institute (T.L.B.), California Pacific Medical Center, San Francisco; Department of Neurology (E.R.E.), VA Medical Center, Boston, MA; Department of Family & Preventive Medicine (E.B.-C.), Division of Epidemiology, University of California, San Diego; and Bone and Mineral Unit (E.S.O.), Oregon Health and Sciences University, Portland.
Address correspondence and reprint requests to Dr. Kristine E. Ensrud, VA Medical Center, One Veterans Drive (111-0), Minneapolis, MN 55417 ensru001{at}umn.edu
Objective: To test the hypotheses that older community dwelling men taking non–enzyme-inducing antiepileptic drugs (NEIAEDs) and those taking enzyme-inducing antiepileptic drugs (EIAEDs) have increased rates of hip bone loss.
Methods: We ascertained antiepileptic drug (AED) use (interviewer-administered questionnaire with verification of use by containers) and measured hip bone mineral density (BMD) (using dual energy x-ray absorptiometry) at baseline and an average of 4.6 years later in a cohort of 4,222 older community-dwelling men enrolled in the Osteoporotic Fractures in Men study. Men were categorized as nonusers (no AED use at either examination, n = 4060), NEIAED user (use of NEIAED only at either examination, n = 100), or EIAED user (use of EIAED only at either examination, n = 62).
Results: After adjustment for multiple potential confounders (age, race, clinic site, health status, pain interfering with work or activity, physical activity, smoking status, alcohol use, total calcium intake, diabetes, chronic kidney disease, vitamin D supplement use, bisphosphonate use, selective serotonin reuptake inhibitor use, inability to rise from a chair, body mass index, and baseline BMD), the average rate of decline in total hip BMD was –0.35%/year among nonusers compared with –0.53%/year among NEIAED users (p = 0.04) and –0.46%/year among EIAED users (p = 0.31). Multivariable adjusted rate of loss was –0.60%/year among men taking NEIAED at both examinations, –0.51%/year among men taking NEIAED at one examination only, and –0.35%/year among nonusers (p for trend = 0.03). Findings were similar at hip subregions.
Conclusion: Use of non–enzyme-inducing antiepileptic drugs was independently associated with increased rates of hip bone loss in this cohort of older community-dwelling men.
Abbreviations: AED = antiepileptic drug; BMD = bone mineral density; CKD = chronic kidney disease; CV = coefficient of variation; DXA = dual energy x-ray absorptiometry; EIAED = enzyme-inducing antiepileptic drugs; IDIS = Iowa Drug Information Service; MrOS = Osteoporotic Fractures in Men; NEIAED = non–enzyme-inducing antiepileptic drugs; PASE = Physical Activity Scale for the Elderly; SOF = Study of Osteoporotic Fractures; SSRI = selective serotonin reuptake inhibitors.
The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, and UL1 RR024140.
Disclosure: The authors report no disclosures.
Received February 18, 2008. Accepted in final form May 23, 2008.
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