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.
