Bone and Hormonal Health in Premenopausal Women with Epilepsy

描述(由申请人提供)：根据疾病控制中心的数据，在美国，骨折是导致残疾的主要原因，癫痫患者的骨折发生率增加了两到四倍。尽管还不完全了解，但与骨骼健康不良相关的因素已成为癫痫患者骨折风险增加的重要组成部分。因此，候选人提出了一个多学科的教育计划和研究项目，以获得适用于癫痫、骨骼和激素健康领域的专业知识。该教育计划将包括哥伦比亚大学梅尔曼公共卫生学院临床研究设计、实施和分析方面的正式课程，以及与内分泌科医学教授伊丽莎白·谢恩博士一起进行的骨代谢纵向指导。此外，她还将作为初级研究员参加Frank‘s Gilliam’s NINDS赞助的名为“癫痫及相关疾病的临床研究”的K24项目。 该研究建议的具体目的是确定癫痫发作活动和细胞色素P450酶诱导的抗癫痫药物治疗对以下方面的单独和联合贡献：1)测量骨密度和骨丢失率；2)通过测量骨转换生化标志物和定量组织形态计量学确定骨重塑活动和骨微结构；3)维生素D-甲状旁腺激素系统，并评估其与骨密度和骨丢失速率的关系；4)生殖激素及其与骨密度和微结构、骨重构和骨丢失速率的关系。我们将通过对控制良好的活动性癫痫患者进行抗癫痫药物治疗的前瞻性3x2析因设计研究来检验我们的假设。设计和分析将区分反复发作和细胞色素P450肝酶诱导的抗癫痫药物的贡献。我们预计，我们的研究结果将为癫痫及其治疗的研究和改进管理的目标提供理论基础。公共卫生声明：癫痫影响1%的人口。接受抗癫痫药物治疗的癫痫患者面临对骨骼健康，最重要的是骨折产生不良影响的风险。通过定义和了解癫痫和抗癫痫药物对骨骼健康的风险，我们将对那些接受抗癫痫药物治疗的癫痫患者产生重大影响。

DESCRIPTION (provided by applicant): 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.