Background: Rapid increases in bone mass occur during Liberty Optimizing calcium absorption (Ca abs) and bone calcium deposition (V0+) 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. This proposal is a logical extension of our recent findings that; 1) changes in calcium metabolism in early puberty are correlated to serum luteimzing hormone (LH) level, ethnicity, family history of osteoporosis, and the genotype of vitamin D receptor polymorphisms, and 2) the addition of small amounts of nondigestible oligosaccharides (NDO) can significantly increase calcium absorption in pubertal children on relatively high calcium-containing diets. 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 V0+ in both boys and girls. In contrast, serum leptin will be negatively correlated with V0+; 2) Putative genetic markers of osteoporosis, including vitamin D receptor polymorphisms, will be significantly correlated to Ca-abs and V0+; 3) The addition of NDO will increase Ca-abs and Vo+ in pubertal children receiving recommended dietary calcium intakes. Study Methods: We will enroll 50 girls and 50 boys who are healthy, 5th to 95th percentile 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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Reproductive Endocrinology Study Section (REN)
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Mcgowan, Joan A
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Baylor College of Medicine
Schools of Medicine
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Abrams, Steven A; Hawthorne, Keli M; Chen, Zhensheng (2013) Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: a double-blind randomized controlled trial. Am J Clin Nutr 97:217-23
Hill, Kathleen M; McCabe, George P; McCabe, Linda D et al. (2010) An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents. J Nutr 140:1983-8
Abrams, Steven A; Hicks, Penni D; Hawthorne, Keli M (2009) Higher serum 25-hydroxyvitamin D levels in school-age children are inconsistently associated with increased calcium absorption. J Clin Endocrinol Metab 94:2421-7
Abrams, Steven A; Griffin, Ian J; Hawthorne, Keli M et al. (2005) Height and height Z-score are related to calcium absorption in five- to fifteen-year-old girls. J Clin Endocrinol Metab 90:5077-81
Abrams, Steven A; Griffin, Ian J; Hawthorne, Keli M et al. (2005) Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents. J Clin Endocrinol Metab 90:5576-81
Abrams, Steven A; Griffin, Ian J; Hawthorne, Keli M et al. (2005) A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 82:471-6
Abrams, S A (2001) Calcium turnover and nutrition through the life cycle. Proc Nutr Soc 60:283-9
Girgis, R; Abrams, S A; Castracane, V D et al. (2000) Ethnic differences in androgens, IGF-I and body fat in healthy prepubertal girls. J Pediatr Endocrinol Metab 13:497-503
Abrams, S A; Copeland, K C; Gunn, S K et al. (2000) Calcium absorption, bone mass accumulation, and kinetics increase during early pubertal development in girls. J Clin Endocrinol Metab 85:1805-9
Abrams, S A; Copeland, K C; Gunn, S K et al. (1999) Calcium absorption and kinetics are similar in 7- and 8-year-old Mexican-American and Caucasian girls despite hormonal differences. J Nutr 129:666-71

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