GENETIC DETERMINANTS OF PEAK BMD IN WOMEN

Indiana Univ-Purdue Univ At Indianapolis, Indianapolis IN

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Abstract

Age related osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength. Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is the most important determinant of bone strength and fracture risk. Between 60 and 80% of the variance in peak bone mineral density of adult Caucasian women has been estimated to be due to heritable factors. Osteoporosis in later life is a function of peak bone mass attained during young adulthood and rate of loss. The goals of this study are to use non- parametric linkage analysis techniques in a large sample of pre- menopausal sister pairs to map, and ultimately clone, genes that play important roles in determining peak BMD. The hypothesis that will be tested are: 1) there are genes that have major effects on attainment of peak bone mineral density; 2) genes with major effects on peak bone mineral density can be cloned using a positional cloning/candidate strategy; 3) the genes that regulate attainment of peak bone mass are the same in African Americans and Caucasians; however, African Americans have a higher frequency of favorable "functional polymorphisms" leading to higher peak BMD and lower fracture rates.