RA Comorbidity Bone Health in Men and African Americans

描述(由申请人提供)： Mikuls博士的职业目标是参与肌肉骨骼疾病的流行病学和结果的有意义的调查，并在此过程中在NIH持续资助的情况下在临床研究方面发展独立的职业生涯。为了达到他的近期和长期目标，申请人提出了一项职业发展计划，该计划主要依赖于具有队列设计、管理和分析的实践研究经验。教学培训将包括研讨会和与经验丰富的NIH资助的调查人员面对面的指导会议。职业发展培训将涵盖与拟议研究项目直接相关的领域。该项目包括对参加美国国立卫生研究院资助的非裔美国人Eady类风湿性关节炎纵向评估联盟(Clear)的RA患者的横断面和前瞻性评估，以及VA类风湿性关节炎(VARA)登记。这项研究的目的是：1)确定患有早期RA的AA患者和患有既往疾病的男性退伍军人中的基线腰椎和股骨颈骨密度(BMD)值以及骨质减少/骨质疏松的患病率；2)确定环境因素和候选等位基因，这些因素和候选等位基因会增加AA早期RA患者和患有既往疾病的男性退伍军人基线骨密度和骨密度丢失的风险。受试者将在登记时和标准随访期(VARA为2年，CLEAR为3至5年)后，通过双能X射线骨密度仪测量股骨和腰椎的骨密度(BMD)。基线骨密度测量将以横断面方式与国家健康和营养检查调查(NHANES)III和霍洛奇公司的标准数据进行比较。患有IRA的绝经后再障女性的骨密度将与预期妇女健康倡议(Will)的数据进行纵向比较。使用多变量模型，我们将检验候选等位基因和环境因素(特别是糖皮质激素的使用)作为BMD和BMD丢失的决定因素的作用。这项队列研究将极大地增强我们对传统上研究不足的人群中与RA相关的骨丢失的了解，并将为Mikuls博士作为独立临床研究者的继续发展提供最佳环境。

DESCRIPTION (provided by applicant): Dr. Mikuls' career goals are to participate in meaningful investigations of the epidemiology and outcomes of musculoskeletal disorders and in the process develop an independent career in clinical research with consistent NIH funding. In order to meet his immediate and long-term objectives, the applicant has proposed a career development plan that relies predominantly on hands-on research experience with cohort design, management, and analysis. Didactic training will include seminars and face-to-face mentoring sessions with experienced NIH-funded investigators. The career development training will cover areas that are directly pertinent to the proposed research project. This project includes cross-sectional and prospective evaluations of patients with RA participating in the NIH-funded Consortium for the Longitudinal Evaluation of African- Americans with eady Rheumatoid Arthritis (CLEAR) the VA Rheumatoid Arthritis (VARA) registries. The aims of the study are: 1) to determine baseline lumbar spine and femoral neck bone mineral density (BMD) values and osteopenia / osteoporosis prevalence among AA patients with early RA and among male veterans with established disease and, 2) to identify environmental factors and candidate alleles, which confer increased risk of reduced baseline BMD and BMD loss over time among AA patients with early RA and among male veterans with established disease. Subjects will undergo bone mineral density (BMD) measurement of the femur and lumbar spine via duel energy x-ray absorptiometry at the time of enrollment and again after a standard period of follow-up (2 years for VARA, 3 to 5 years for CLEAR). Baseline BMD measurements will be compared in a cross-sectional manner with normative data from the National Health and Nutrition Examination Survey (NHANES) III and from Hologic, Inc. Longitudinal comparisons in BMD will be made among post-menopausal AA women with IRA with data from the prospective Women's Health Initiative (WIll). Using mulitvadable modeling we will examine the role of candidate alleles and environmental factors (particularly glucocorticoid use) as determinants of BMD and BMD loss. This cohort study will greatly enhance our understanding of RA-associated bone loss in traditionally understudied populations and will provide an optimal context for Dr. Mikuls' continued development as an independent clinical investigator.