Zinc and Bone Turnover Study in Adolescent Females

The purpose of the study is to determine the effects of zinc supplementation on bone growth over four weeks. Participants will agree to attend two visits to our laboratory and at each will complete blood and urine samples, questionnaires related to diet and physical activity and will receive a bone scan at the first appointment.

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 Insulin-like growth factor one (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 4 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.

Serum Zinc will be measured at the Baseline and 4 week time point to determine effects of placebo vs. supplement.

Plasma IGF-1 and IGFBP-3 will be measured at Baseline and 4-weeks and analyzed using ELISA to determine changes.

Inclusion Criteria: Healthy Female Ages 9-11 Pre-menarchal Caucasian or African American Exclusion Criteria: Menses Disease known to affect bone Drugs known to affect bone Vitamin/mineral supplements

Lobene AJ, Kindler JM, Jenkins NT, Pollock NK, Laing EM, Grider A, Lewis RD. Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents. J Nutr. 2017 Jul;147(7):1296-1300. doi: 10.3945/jn.117.248013. Epub 2017 Jun 7.

Kindler JM, Pollock NK, Laing EM, Jenkins NT, Oshri A, Isales C, Hamrick M, Lewis RD. Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls. J Clin Endocrinol Metab. 2016 Jan;101(1):199-205. doi: 10.1210/jc.2015-3451. Epub 2015 Nov 17.

Berger PK, Pollock NK, Laing EM, Chertin V, Bernard PJ, Grider A, Shapses SA, Ding KH, Isales CM, Lewis RD. Zinc Supplementation Increases Procollagen Type 1 Amino-Terminal Propeptide in Premenarcheal Girls: A Randomized Controlled Trial. J Nutr. 2015 Dec;145(12):2699-704. doi: 10.3945/jn.115.218792. Epub 2015 Oct 21.