? We have conducted a series of studies to evaluate calcium and bone mineral status in children. Subsequent to our competitive renewal in 2001, we are beginning the 8th year of our studies to evaluate methods of improving bone mineralization in children. Our goal is to identify dietary factors to enhance calcium absorption and bone mineralization in vulnerable populations. We use stable isotope methods that are safe and applicable globally to assess mineral metabolism (calcium, zinc, magnesium, iron, copper). We propose to extend our research to evaluate dietary antecedents of mineral deficiency in a unique population of children with severe calcium deficiency-related rickets in Nigeria. We propose to develop a novel collaboration for conducting comprehensive mineral research. Hypotheses: Our overall hypotheses are that clinical and radiological signs of rickets in Nigeria are primarily related to dietary mineral insufficiency, especially in the presence of dietary inhibitors of mineral absorption. Therefore, enhanced mineral absorption should be possible by decreasing the effects of these inhibitors. Although calcium is the most important bone mineral, it is well recognized that other minerals, including zinc, are crucial for growth and bone mineralization. Inadequate zinc status may contribute to slow overall growth which may be a particular problem in Nigeria due to the high phytate content of the diets. It may be optimal, therefore, to provide mineral supplementation to children receiving typical Nigerian meals or to reduce the phytate contents of the meal. Specifically, we hypothesize that; 1) Supplemental calcium and zinc will be absorbed significantly better when given without a meal than when given with a typical Nigerian meal; 2) Dephytinization of a typical meal will enhance calcium and zinc absorption. Study Methods: We will enroll 18 children age 2-8 yrs with clinical and biochemical evidence of rickets and 18 age- and gender-matched healthy, children in Jos, Nigeria. Children will receive therapy with calcium and vitamin D for 6 weeks prior to measurement of mineral absorption. A multiple stable isotope method will be used to compare calcium and zinc absorption from 250 mg calcium and 10 mg zinc given with and without a typical Nigerian meal. One week later, the study will be repeated evaluating the effects of dephytinization on mineral absorption. At that time, the subjects will be randomized to receive one of two different popular weaning foods. Absorption from these foods will be measured both with and without dephytinization prior to the meal. After the studies, children with rickets will receive clinical treatment for their disease. Conclusions: We hypothesize that dephytinization will lead to markedly improved calcium and zinc absorption. Fractional absorption of calcium and zinc after dephytinization will be similar to that from supplementation given without a meal. This may be important in developing strategies for mineral supplementation in Nigeria. Key technologies including stable isotope absorption techniques and methods for measuring PTH and 25(OH)D concentrations will be transferred to the Nigerian research team. There are no other research centers in Africa with the capacities to conduct such studies and the ability to prepare samples for mass spectrometric analysis of multiple minerals. Comparisons of calcium and zinc absorption will be possible between children in Nigeria and age and gender-matched African-American children living in Houston, TX. Training programs in the US and Nigeria will enable further studies of mineral requirements, including calcium and zinc kinetic measurements to be conducted in Nigeria. ? ?

National Institute of Health (NIH)
Fogarty International Center (FIC)
Small Research Grants (R03)
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International and Cooperative Projects 1 Study Section (ICP)
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Primack, Aron
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Baylor College of Medicine
Schools of Medicine
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Thacher, Tom D; Obadofin, Michael O; O'Brien, Kimberly O et al. (2009) The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets. J Clin Endocrinol Metab 94:3314-21
Thacher, Tom D; Aliu, Oluseyi; Griffin, Ian J et al. (2009) Meals and dephytinization affect calcium and zinc absorption in Nigerian children with rickets. J Nutr 139:926-32