This application has two major goals. The first is to extend follow-up in the Michigan Bone Health Study (MBHS) population for an additional 4 annual examinations. The 10-year MBHS longitudinal study, initiated in 1992, has characterized the natural history of musculoskeletal status and its alteration among women (aged 25-45 at their baseline) whose hormone status is changing because of menopause and obesity. Secondly, we propose to evaluate the influence of the metabolic environment generated by obesity on musculoskeletal status and physical functioning with a focus on oxidative stress and inflammation.
The aims are to: A) Describe the 13-year rate of change in body composition and the following: 1) rate of pre, perimenopausal and postmenopausal bone loss including bone mineral density (BMD), bone width, and bone mineral concentration, 2) incidence and prevalence of OAK, and 3) change in physical functioning. B) Describe changes in ovarian (i.e.. estradiol') and non-ovarian hormone concentrations (i.e., androstenedione) over a 13-year period and relate the hormone changes to 1) rate of pre, perimenopausal and postmenopausal bone loss, 2) incidence and prevalence of OAK, and 3) change in physical functioning in mid-aged women. C) Evaluate the potential mechanisms for the impact of change in fat and lean mass by assessing whether an exaggerated inflammatory state coupled with increasingly greater insulin resistance (seen in obesity) increases the likelihood of greater BMD loss, OA progression, and greater physical limitation. Data has been collected annually from the 604 enrollees of MBHS ten times over the period 1992/93 to 2002/3 and excluding 1996/1997. More than 60% of the study population has been assessed at all ten evaluations and 84% of the population had at least eight (8) of the ten (10) evaluations. Results related to the three major outcomes have been presented in more than 30 publications. The proposed 4 additional yearly assessments will cover a 13-year period that includes the reproductive life span of women to the postmenopause. Annual assessments will include BMD, measures of physical functioning, phlebotomy and urine collection to allow assessment of hormones and inflammation markers. X-rays will be taken in the 2nd-3nd year of the proposed time period to have a series of 4 hand and knee films over the time interval of interest. Stored specimens (serum and urine) will be assayed to have alternative year measures of selected hormones, inflammation markers, glucose and insulin over the 13-year period. This study will provide a unique setting to evaluate the impact of an aging related process (menopause) and an environmentally related process (increasing obesity) on the development and progression of musculoskeletal disease and their potential for contributing to degree of functioning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR051384-02
Application #
7046172
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Lester, Gayle E
Project Start
2005-04-01
Project End
2010-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
2
Fiscal Year
2006
Total Cost
$512,032
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Berent-Spillson, Alison; Marsh, Courtney; Persad, Carol et al. (2017) Metabolic and hormone influences on emotion processing during menopause. Psychoneuroendocrinology 76:218-225
Rillamas-Sun, Eileen; Harlow, Siobán D; Randolph Jr, John F (2014) Grandmothers' smoking in pregnancy and grandchildren's birth weight: comparisons by grandmother birth cohort. Matern Child Health J 18:1691-8
Zheng, Huiyong; Sowers, Maryfran; Karvonen-Gutierrez, Carrie et al. (2012) Semiparametric Mixed Effect Model with Application to the Longitudinal Knee Osteoarthritis (OAK) Data. J Syst Cybern Inf 10:87-93
Karvonen-Gutierrez, C A; Sowers, Mf R; Heeringa, S G (2012) Sex dimorphism in the association of cardiometabolic characteristics and osteophytes-defined radiographic knee osteoarthritis among obese and non-obese adults: NHANES III. Osteoarthritis Cartilage 20:614-21
Rillamas-Sun, Eileen; Sowers, MaryFran R; Harlow, Sioban D et al. (2012) The relationship of birth weight with longitudinal changes in body composition in adult women. Obesity (Silver Spring) 20:463-5
Zheng, Huiyong; Sowers, Maryfran; Randolph Jr, John F et al. (2011) An Integrated Quantitative Methodology to Longitudinally Characterize Complex Dynamic Processes Associated with Ovarian Aging and the Menopausal Transition. J Syst Cybern Inf 9:13-21
Griffin, Flojaune C; Gadegbeku, Crystal A; Sowers, MaryFran R (2011) Vitamin D and subsequent systolic hypertension among women. Am J Hypertens 24:316-21
Silver, Monica K; O'Neill, Marie S; Sowers, Maryfran R et al. (2011) Urinary bisphenol A and type-2 diabetes in U.S. adults: data from NHANES 2003-2008. PLoS One 6:e26868
Sowers, MaryFran R; Karvonen-Gutierrez, Carrie A (2010) The evolving role of obesity in knee osteoarthritis. Curr Opin Rheumatol 22:533-7
Sowers, MaryFran R; Zheng, Huiyong; Jannausch, Mary L et al. (2010) Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause. J Clin Endocrinol Metab 95:2155-62

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