Zinc and Bone Turnover Study in Adolescent Females

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Supplemental Zinc and Bone Turnover in Early Pubertal Females

Conditions
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Bone, Growth, Osteoporosis

Intervention / Treatment
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* Dietary Supplement: Zinc Sulfate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zinc Sulfate<br>Subjects enrolled in this arm will receive 9mg elemental zinc (23mg zn sulfate)/day for 4 weeks. | Dietary Supplement: Zinc Sulfate<br>* 9mg elemental zinc via 23mg zinc sulfate/day<br>|
| Placebo Comparator: Cellulose Pill<br>Subject enrolled in this arm will receive a placebo. | Dietary Supplement: Placebo<br>* Cellulose pill given as placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Zinc | Serum Zinc will be measured at the Baseline and 4 week time point to determine effects of placebo vs. supplement. | 4 weeks | 
| Plasma IGF-1 and IGFBP-3 | Plasma IGF-1 and IGFBP-3 will be measured at Baseline and 4-weeks and analyzed using ELISA to determine changes. | 4 weeks | 
| procollagen type 1 amino-terminal propeptide (P1NP) | Bone turnover marker procollagen type 1 amino-terminal propeptide, | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zinc, Bone, Adolescents, Growth