Abstract

Osteoporosis is a major cause of disability in the United States. Numerous factors contribute to the decline in bone mineral density (BMD) that characterizes this disease, and the importance of heredity is now widely appreciated. We evaluated the joint contributions of genes and environmental factors on variation in BMD in 895 participants of the San Antonio Family Osteoporosis Study (SAFOS). Participants of the SAFOS ranged in age from 18 to 96 years and were members of 34 large families of Mexican American ancestry. BMD was measured at the spine, hip, and forearm by dual-energy X-ray absorptiometry. Information about medical history, lifestyle habits, dietary intake, and physical activity patterns was obtained by questionnaire. Age and body mass index were strongly associated with BMD at nearly every site; these and other measured risk factors accounted in aggregate for up to 46% of the total variation in BMD. In general, the environmental risk factors accounted for proportionately more of the total variation in BMD in men than in women. Genes accounted for 65–80% of the residual variation in spine and hip BMD, and 25–55% of the residual variability in forearm BMD. Although residual heritabilities were generally comparable between men and women across all ages combined, heritabilities at all sites tended to be higher in premenopausal women than in men younger than 50 years of age. Identifying the individual genes involved will shed insights into the processes that govern bone remodeling and may suggest strategies for the prevention of osteoporosis.

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