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. Rapid increases in bone mass occur during puberty. Optimizing calcium absorption (Ca-abs) and bone calcium deposition (Vo+) during puberty can enhance peak bone mass and ultimately decrease the lifetime risk of osteoporosis. In this study, we will determine the influence of hormonal, genetic and dietary factors that lead to maximal Ca-abs and Vo+ in pubertal boys and girls. Hypotheses: Our overall hypotheses are that dynamic changes in mineral metabolism in early adolescence are based on identifiable hormonal and genetic factors and that specific nutritional interventions can enhance bone mass accumulation. Specifically, in this proposal we will evaluate the following: 1) Early nighttime increases in pubertal hormones will be closely correlated to Ca-abs and Vo+ in both boys and girls. In contrast, serum leptin will be negatively correlated with Vo+; 2) Putative genetic markers of osteoporosis, including vitamin D receptor polymorphisms, will be significantly correlated to Ca-abs and Vo+; 3) The addition of NDO will increase Ca-abs and Vo+ in pubertal children receiving recommended dietary calcium intakes. We will enroll 50 girls and 50 boys who are healthy, 10th to 90th %ile body mass index for age, and Tanner Stage 2 or 3. They will participate in comprehensive dual-tracer calcium stable isotopic kinetic studies. Results will be compared with pubertal hormonal studies, biochemical bone turnover markers, and dual-energy X-ray absorptiometry (DXA) measures of whole body and regional bone mineral content. Genetic markers related to bone mass will be assessed and related to both hormonal and calcium kinetic measurements. After these baseline studies, subjects will be randomized to receive calcium fortified foods either with or without added NDO. Calcium absorption will be measured again after 2 months. After 12 months, the baseline calcium kinetic, hormonal and DXA studies will be repeated to assess the effects both of pubertal development and the dietary intervention. At the conclusion of that study, supplementation with NDO will be stopped and a final DXA study performed 12 months later to assess whether bone mass differences identified during supplementation were maintained post-intervention. Conclusions: By identifying the relationships among hormonal changes of puberty, genetics and calcium metabolism, the characteristics leading to maximal calcium absorption and utilization can be identified. These insights will enable interventional strategies to enhance bone mass to be specifically related to identifiable population characteristics, with the ultimate goal of decreasing the incidence and severity of bone loss and osteoporosis.
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