Significant accomplishments have been achieved with respect to our understanding of calcium and vitamin D and skeletal health, yet a body of scientific evidence has also identified understudied nutrients that have potential for reducing the burden of osteoporosis. Zinc has important roles in bone metabolism and there are indications from animal and human studies that beyond correcting skeletal and growth impairments under deficiency conditions, supplementation with zinc may have a bone health-promoting role. It has been postulated that the action of zinc on bone metabolism is partially mediated by IGF-I. Prior to undertaking a long-term bone trial, a short-term zinc supplementation trial is proposed to first determine if zinc alters intermediate markers of bone metabolism in healthy, early pubertal females (9-10.5 years of age). We hypothesize that healthy females receiving 24 mg zinc /day over 3 weeks will have elevated serum markers of bone formation and plasma growth factors compared to those receiving placebo. We further hypothesize that the differences between the zinc and placebo groups will vary by race. To test these hypotheses, we will screen early pubertal females to assure similar maturational status and conduct a 3-week, randomized, double-blind, placebo-controlled trial with a zinc supplementation (zinc sulfate; n=80) and a placebo (n=80) arm. The groups will be further divided by race (non-Hispanic White and non-Hispanic Black; n=40 per group).
The specific aims are to determine if early pubertal females supplemented with zinc compared to those receiving placebo will have: 1) greater increases in markers of bone turnover favoring bone formation; 2) greater increases in plasma IGF-1 and IGFBP-3; and 3) changes in bone turnover markers, IGF-1 and IGFBP-3 that differ by race. In addition, anthropometric measures, maturity offset, sexual maturation, erythrocyte superoxide dismutase activity, ceruloplasmin, dietary intakes and physical activity will be determined. Findings from this study will provide preliminary evidence of whether supplementation with zinc is a viable nutrition strategy to improve biochemical indices of bone turnover and growth factors in young females. Moreover, the results will help determine if a long-term clinical bone trial is warranted to more definitely assess the potential for supplemental zinc to reduce the risk for osteoporosis. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD054630-02
Application #
7363672
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Winer, Karen
Project Start
2007-02-20
Project End
2011-01-31
Budget Start
2008-02-01
Budget End
2011-01-31
Support Year
2
Fiscal Year
2008
Total Cost
$72,275
Indirect Cost
Name
University of Georgia
Department
Nutrition
Type
Other Domestic Higher Education
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Lobene, Andrea J; Kindler, Joseph M; Jenkins, Nathan T et al. (2017) Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents. J Nutr 147:1296-1300
Kindler, J M; Pollock, N K; Laing, E M et al. (2016) Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls. J Clin Endocrinol Metab 101:199-205
Grider, Arthur; Lewis, Richard D; Laing, Emma M et al. (2015) Zinc affects miR-548n, SMAD4, SMAD5 expression in HepG2 hepatocyte and HEp-2 lung cell lines. Biometals 28:959-66