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.


Background: Data have shown that healthy children and adolescents have an inadequate intake of zinc, an essential nutrient for growth. It is unclear whether zinc supplementation can enhance bone health during this rapid period of growth and development.

Objective: The primary aim of this study was to determine the effect of zinc supplementation on biochemical markers of bone turnover and growth in girls entering the early stages of puberty. The secondary aim was to test moderation by race, body mass index (BMI) classification, and plasma zinc status at baseline.

Methods: One hundred forty seven girls aged 9-11 y (46% black) were randomly assigned to a daily oral zinc tablet (9 mg elemental zinc; n = 75) or an identical placebo (n = 72) for 4 wk. Fasting plasma zinc, procollagen type 1 amino-terminal propeptide (P1NP; a bone formation marker), carboxy-terminal telopeptide region of type 1 collagen (ICTP; a bone resorption marker), and insulin-like growth factor I (IGF-I) were assessed at baseline and post-test. Additional markers of bone formation (osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline) were also measured.

Results: Four weeks of zinc supplementation increased plasma zinc concentrations compared with placebo [mean change, 1.8 μmol/L (95% CI: 1.0, 2.6) compared with 0.2 μmol/L (95% CI: -0.3, 0.7); P < 0.01]. Zinc supplementation also increased serum P1NP concentrations compared with placebo [mean change, 23.8 μmol/L (95% CI: -14.9, 62.5) compared with -31.0 μmol/L (95% CI: -66.4, 4.2); P = 0.04). There was no effect from zinc supplementation on osteocalcin, ICTP, pyridinoline, deoxypyridinoline, or IGF-I. There was no moderation by race, BMI classification, or plasma zinc status at baseline.

Conclusions: Our data suggest that 4 wk of zinc supplementation increases bone formation in premenarcheal girls. Further studies are needed to determine whether supplemental zinc can improve childhood bone strength. This trial was registered at clinicaltrials.gov as NCT01892098.

Keywords: bone; bone turnover; children; growth; zinc.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / urine
  • Biomarkers / blood
  • Body Weight
  • Bone Development / drug effects*
  • Bone Development / physiology
  • Bone Remodeling / drug effects
  • Bone Remodeling / physiology
  • Child
  • Collagen Type I / blood
  • Dietary Supplements*
  • Female
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Osteocalcin / blood
  • Peptide Fragments / blood*
  • Peptides / blood
  • Placebos
  • Procollagen / blood*
  • Puberty / physiology*
  • Zinc / administration & dosage*
  • Zinc / blood


  • Amino Acids
  • Biomarkers
  • Collagen Type I
  • Peptide Fragments
  • Peptides
  • Placebos
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Osteocalcin
  • pyridinoline
  • Insulin-Like Growth Factor I
  • deoxypyridinoline
  • Zinc

Associated data

  • ClinicalTrials.gov/NCT01892098