GENETICS OF BONE STRENGTH IN MEN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related osteoporotic fracture, particularly hip fracture, is a major health problem in the United States and worldwide. Age-related decrease in bone strength is a major risk factor for osteoporotic fracture. Components of bone strength are highly heritable, and in our studies using premenopausal sister pairs, we have detected linkage to several measures of both bone mass and bone structure. Heritability studies on measure of bone strength in men are very limited. Futhermore, studies in mice suggest that sex specific genes may underlie differences in bone strength between men and women. The hypothesis that will be tested in this study is that in men bone mass, bone structure , bone quality and bone turnover have components that are genetically determined and are similar in magnitude to those we have established in women. However, while many loci will be the same in both sexes, certain loci will be sex specific. The skeletal sites that are being measured by dual X-ray absorptiometry are right femoral neck, trochanter and wards, lumbar vertebrae L2 to L4 and total body. Radiographs of the lower pelvis with upper femura in 15 degrees internal rotation are taken on standard X-ray equipment. All structural measurements are made on the right hip (the same measured by DXA) using a digital caliper. Fasting blood and urine will be collected for measurement of calcium regulating hormones and biochemical markers of bone turnover. Anthropometrics are measured on dedicated instruments; total body lean and fat are measured by DXA. The questionnaires include personal, family and medical history, medication history, smoking, physical activity and dietary questionnaires. All questionnaires have been verified and have been use over the last five years in GCRC Protocol 578.