The major goal of the proposed research is to investigate the determinants of bone dynamics in young women in order to develop strategies to prevent osteoporosis. Recent studies have confirmed that 1) peak bone density is a predictor of osteoporosis risk; 2) 50% of adult bone mass in females is acquired during adolescence; and 3) for most women, 95% of adult peak bone mass is achieved near the age of 20. The present study (in the first award period) was designed such that he cohort was homogeneous at entry at age 12 with respect to age, race, and pubertal development. BMI and baseline bone density values were used to balance the study groups with respect to genetic influences on bone. In this study, we used a randomized double- blind, placebo-controlled trial and determined that calcium supplementation of 350 mg/d calcium from calcium citrate malate initiated at either age 12 or at age 14 produces a 1.5% annualized increase (p=0.005) in normal bone gain. This increase, if continued for three years and maintained to peak bone mass, should lead to a significant reduction in risk of future osteoporotic fractures. We evaluated the interrelationships among physical activity, physical fitness, nutrient intake, pubertal progression and bone development in girls from age 12 through age 15 and determined that among well-nourished girls cumulative estrogen exposure and dietary calcium intake are the most powerful determinants of bone gain during early and mid-adolescence. We propose to continue to study the subjects from age 16-21 and to determine how dietary, endocrine and lifestyle factors affect bone dynamics and acquisition of peak bone mass. Of the 112 original volunteers, 90 remain in the present cohort and of these 89 (00%) are interested in remaining in the study. During the next 5 years, subjects will not receive calcium supplement or placebo pills;' and we will 1) Determine whether the increase in bone gain due to calcium supplementation from age 12 or from age 14 results increase in adult bone mass; 2) Determine how late adolescent bone gain is related to--a) cumulative adolescent dietary calcium intake; b) physical activity and physical fitness patterns; c) urinary collagen cross-link excretion; d) changes in body composition and anthropometric variables; and e) late adolescent and early adult reproductive hormone levels; 3) Quantify the effect of adolescent menstrual history, cumulative estrogen exposure and cumulative calcium intake on peak bone mass. Continuation of the longitudinal study design is essential to answering these questions. Each subject will be seen yearly. Comprehensive bone and body composition measurements will be made by dual energy x-ray absorptiometry (DEXA). We will also obtain medical and menstrual histories, anthropometric measurements, reproductive hormone measurement from serum samples, nutrient analyses from three day diet records, physical activity assessed by questionnaire, physical fitness measured by cycle ergometry, and bone-specific collagen crosslink excretion measured from urine specimens. The findings from this study will lead to a grater understanding of how modifiable life style factors affect peak bone mass dynamics. Such knowledge is essential to the development of bone health promotion strategies for young American women.
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