Based on Centers for Disease Control data, fractures are a leading cause of disability in the United States, and are increased two to four fold in persons with epilepsy. Although incompletely understood, factors related to poor bone health have emerged as important components of the increased risk for fracture in epilepsy. Therefore, the candidate proposes a multidisciplinary educational program and research project to gain expertise in areas applicable to epilepsy, and bone and hormonal health. The educational program will include formal coursework in clinical study design, implementation, and analysis at the Columbia University Mailman School of Public Health and also a structured longitudinal preceptorship in bone metabolism with Dr. Elizabeth Shane, Professor of Medicine in the Endocrine Division. In addition, she will participate as a junior investigator in Dr. Frank's Gilliam's NINDS sponsored K24 program entitled, """"""""Clinical Research in Epilepsy and Related Disorders. ? ? The specific aims of the research proposal are to determine the separate and combined contribution of seizure activity and treatment with cytochrome P450 enzyme-inducing antiepileptic drugs, on 1) measurements of bone mineral density and rates of bone loss; 2) bone remodeling activity and bone microarchitecture by both measurement of biochemical markers of bone turnover and quantitative histomorphometry; 3) the vitamin D-parathyroid hormone system and evaluate its relationship to bone mineral density and rates of bone loss; 4) reproductive hormones and their relationship to bone mineral density and microarchitecture, bone remodeling and rates of bone loss. We will test our hypotheses through a prospective 3X2 factorial design study of subjects with well controlled and active epilepsy on antiepileptic drug treatment. The design and analysis will differentiate the contributions of recurrent seizures and cytochrome P450 hepatic enzyme inducing antiepileptic drugs. We anticipate that the results of our study will provide a rationale basis for targets in research and improved management of consequences of epilepsy and its treatment. Public Health Statement: Epilepsy affects 1% of the population. Persons with epilepsy treated with antiepileptic drugs are at risk for adverse effects on bone health, most importantly fracture. By defining and understanding the risk that epilepsy and antiepileptic drugs have on bone health, we will significantly impact those persons with epilepsy treated with antiepileptic drugs. ? ? ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Mentored Patient-Oriented Research Career Development Award (K23)
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Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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Mcgowan, Joan A
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Pack, Alison M (2012) Falls and fractures in patients with epilepsy: is there an increased risk? If so, why? Neurology 79:119-20
Pack, Alison M; Morrell, Martha J; McMahon, Don J et al. (2011) Normal vitamin D and low free estradiol levels in women on enzyme-inducing antiepileptic drugs. Epilepsy Behav 21:453-8