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Apparent Efficacy of Food-Based Calcium Supplementation in Preventing Rickets in Bangladesh

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Abstract

To determine whether increased Ca intakes can prevent rickets in a susceptible group of children living in a rickets-endemic area of Bangladesh, we conducted a 13-month long, double-blind, clinical trial with 1-to 5-year-old children who did not present with rickets but ranked in the upper decile of plasma alkaline phosphatase (AP) activity of a screening cohort of 1,749 children. A total of 158 children were randomized to a milk-powder-based dietary supplement given daily, 6 days/week, and providing either 50, 250, or 500 mg Ca, or 500 mg Ca plus multivitamins, iron, and zinc. Upon initial screening, 194 healthy children presented with no rachitic leg signs and had serum AP in the upper decile (>260 u/dl) of the cohort. When 183 of those subjects were re-screened after a 7-month pre-trial period, 23 (12.6%) had developed rachitic leg signs, suggesting an annual risk of 21.5% in this cohort. Of those still not presenting with leg signs and completing 13 months of dietary intervention, none showed rachitic leg signs, none showed significant radiological evidence of active rickets, and all showed carpal ossification normal for age after that intervention. These results are consistent with even the lowest amount of supplemental Ca (50 mg/day) being useful in supporting normal bone development in this high-risk population.

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Notes

  1. Actual analysis: 47 ± 5 mg Ca, 21 ± 3 mg Mg, 0.4 ± 0.1 mg Zn, 1 ± 0.2 mg Fe, 0.4 ± 0.1 mg Cu; also formulated to provide 2.6 g protein and 95 kcal.

  2. Actual analysis: 232 ± 20 mg Ca, 37 ± 5 mg Mg, 0.5 ± 0.1 mg Zn, 0.8 ± 0.3 mg Fe, 0.4 ± 0.1 mg Cu; also formulated to provide 2.6 g protein and 95 kcal.

  3. Actual analysis: 528 ± 35 mg Ca, 84 ± 10 mg Mg, 1.2 ± 0.2 mg Zn, 1.5 ± 2 mg Fe, 0.9 ± 1.2 mg Cu; also formulated to provide 5.1 g protein and 184 kcal.

  4. Actual analysis: 573 ± 52 mg Ca, 81 ± 15 mg Mg, 2.1 ± 0.2 mg Zn, 11.6 ± 1.5 mg Fe, 0.9 ± 1.2 mg Cu; also formulated to provide 640 mg RE all-trans-retinyl palmitate, 4 mcg cholecalciferol, 8 mg all-rac-tocopheryl acetate, 48 mg ascorbic acid, 1.1 mg thiamin, 0.8 mg riboflavin, 14.4 mg niacin, 1.6 mg pyridoxine, 160 mcg folate, 0.8 mg vitamin B12, 0.12 mg D-biotin, 4.8 mg pantothenic acid, 5.1 g protein and 184 kcal.

  5. The Committee provides human subjects oversight for the Grand Forks Human Nutrition Research Center.

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Acknowledgments

This study was supported by a grant from the Rockefeller Foundation and support from US Agency for International Development through the Soil Management CRSP and the Cornell International Institute for Food and Agricultural Development. The intervention supplements were formulated and generously provided by SmithKline Beecham, through the agency of Dr. Bruce Daggy. The authors are indebted to the children and their families who gave of their time and hospitality for this work. We gratefully acknowledge the essential contributions of the following persons: Mr. Andrew Daly, who served as project coordinator in Bangladesh,; Ms. Afzalunessa, Ms. Hamida Begum, Ms. Momtaz Begum, Ms. Salma Begum, Ms. Farhana Haseen, Ms. Lucky Parveen, Ms. Asia Siddiqua, who served as field workers; Mr. Shahidul Haque and Mr. Mohammed Noman, SARPV, who provided field support; Dr. Steve Abrams, USDA Children’s Nutrition Research Center, Baylor College of Medicine, who provided advice concerning experimental design; Ms. Sandy Gallagher, USDA Grand Forks Human Nutrition Research Center (GFHNRC), who provided assistance in some clinical chemical analyses; Mr. Craig Lacher and Mr. Terry Schuler, GFHNRC, who provided assistance with the instrumental analyses of minerals; Ms. Kay Keehr, GFHNRC, who provided assistance in the digital analysis of radiographs; Ms. LuAnn Johnson, GFHNRC, who provided statistical analytical assistance; Dr. Craig Meisner, International Wheat and Maize Improvement Center, Bangladesh, who provided logistical support. We are particularly indebted to Mr. Mizanur Rhaman, the field manager of this trial, whose recent death is felt by the entire team.

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Correspondence to Gerald F. Combs Jr..

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Contributors: GFC was the principal investigator of the study; NH was the co-PI and, as such, assisted in the planning of the intervention trial and was responsible for implementing its implementation; ND, DS and SK provided medical oversight, radiography and clinical chemical analyses; PF participated in designing the study and conducted blind evaluations of radiographs; CH performed radiographic analyses of bone morphology; JW performed chemical analyses.

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Combs, G.F., Hassan, N., Dellagana, N. et al. Apparent Efficacy of Food-Based Calcium Supplementation in Preventing Rickets in Bangladesh. Biol Trace Elem Res 121, 193–204 (2008). https://doi.org/10.1007/s12011-007-8053-z

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