The proposed R-01 builds upon the Study of Woman's Health Across the Nation (SWAN) osteoporosis project. SWAN is a multi-center, longitudinal study, designed to characterize the biological and psychosocial changes that occur during the menopausal transition in a community-based sample of African-American, Caucasian, Chinese, Japanese, and Hispanic women. An overarching goal of SWAN is """"""""to elucidate factors that differentiate women most susceptible to long-term pathophysiological consequences of ovarian hormone deficiency from women who are protected."""""""" One of the key physiological consequences of ovarian aging that was specifically targeted in SWAN was change in skeletal mass. Thus, five of the seven SWAN clinical sites are making annual measures of bone mineral density (BMD) by Dual X-ray Absorptiometry (DXA). All SWAN ethnic groups except the Hispanic women are represented in the SWAN bone project. However, BMD is only one of several factors that contribute to bone strength;bone structural properties including size, thickness, shape and spatial distribution of bone mass in a cross-section also contribute. Additionally, fractures result from an imbalance between bone strength and the load the bone bears. Thus, fracture risk depends on bone strength relative to the load it has to bear;the latter depends on body size. We propose to measure hip geometry and strength using the Hip Structural Analysis Program developed by Dr. Thomas Beck, and the Composite Strength Indices developed by Dr. Arun Karlamangla. We also propose to compare hip structural parameters and strength indices obtained from areal DXA scans with those obtained from 3-dimensional imaging using Quantitative Computed Tomography (QCT) on a subset of women.
The specific aims of our study are to: 1) Determine the correlations between areal DXA based estimates of hip geometry and strength with QCT measures;2) Determine the direction and magnitude of ethnic differences in femoral neck size, structure, and composite strength indices at baseline;3) Identify predictors of baseline femoral neck size, structure, and strength;4) Determine the rate of longitudinal change in femoral neck size and structural and composite strength indices with aging and with transition through menopause in different ethnic groups;5) Identify factors associated with longitudinal changes in femoral neck size and strength indices and to compare their effects on size and strength with their effects on bone density;6) Test the hypothesis that baseline femoral neck size and structural and composite strength indices predict incident fracture risk in midlife women. Our long-term objective is to substantially improve our understanding of the impact of aging and menopause on measures of hip size, structure, and strength in a well-characterized multiethnic cohort of mid-life women.
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