Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial

Am J Clin Nutr. 2013 Oct;98(4):960-71. doi: 10.3945/ajcn.112.049221. Epub 2013 Aug 14.


Background: Patients with thalassemia major (Thal) frequently have low plasma zinc, which has been associated with low bone mass.

Objective: The objective was to determine the effect of zinc supplementation on bone mass in patients with Thal.

Design: Forty-two subjects (21 females aged 10-30 y) with Thal and low bone mass were randomly assigned to receive 25 mg Zn/d or placebo. Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed by using dual-energy X-ray absorptiometry, and fasting blood was collected for the measurement of plasma zinc at 0, 12, and 18 mo.

Results: Thirty-two subjects, 81% of whom were transfusion dependent, completed the study (mean ± SD: 17.1 ± 5.2 y). Plasma zinc was ≤70 μg/dL in 11 subjects at baseline and increased significantly with zinc supplementation (P = 0.014). Use of intention-to-treat analysis and linear models for longitudinal data, adjusted for baseline and pubertal stage, showed that the zinc group had significantly greater increases in whole-body BMC (adjusted mean ± SE: 63 ± 15 g; P = 0.02), and aBMD (0.023 ± 0.006 g/cm(2); P = 0.04) than did the placebo group after 18 mo. Furthermore, adjusted spine and hip aBMD z scores each decreased by 0.3 SDs (both P = 0.04) in the placebo compared with the zinc group over the 18-mo study.

Conclusions: In young patients with Thal, zinc supplementation resulted in greater gains in total-body bone mass than did placebo. Zinc was well tolerated and is worthy of investigation in larger trials in Thal patients across a range of ages and disease severity. This trial was registered at clinicaltrials.gov as NCT00459732.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Bone Density / drug effects*
  • Child
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Placebos
  • Young Adult
  • Zinc / administration & dosage*
  • Zinc / blood
  • beta-Thalassemia / drug therapy*
  • beta-Thalassemia / physiopathology


  • Placebos
  • Zinc

Associated data

  • ClinicalTrials.gov/NCT00459732