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

Abstract

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.

Figures

FIGURE 1.

Recruitment and randomization scheme for subjects with thalassemia enrolled in the Think Zinc Trial.

FIGURE 2.

Fasting plasma zinc (A) and spot morning urinary zinc (B) by time and intervention group in subjects in the zinc-supplemented group (n = 18) and the placebo-supplemented group (n = 14) who completed the 18-mo intervention. Line = median; box = 25%–75%; bars = 5th to 95th. A significant increase was observed in plasma zinc at 3 mo and 6 mo compared with baseline in the zinc group, noted by an asterisk within the box plot, P < 0.014 (repeated-measures ANOVA). A trend toward an increase in urinary zinc excretion was observed from baseline in the zinc-supplemented group, P = 0.08 (repeated-measures ANOVA).

FIGURE 3.

Percentage change in lateral spine BMC (A), lateral spine aBMD (B), whole-body BMC (C), and whole-body aBMD (D) assessed by dual-energy X-ray absorptiometry from baseline to 12 and 18 mo, by intervention group [zinc (n = 20), placebo (n = 17)], in subjects who completed ≥12 mo of the study. P value for the mixed-effects linear model after control for baseline: group × time interaction (NS). P = 0.009 for difference by group for lateral spine BMC, P = 0.027 for lateral spine aBMD, P = 0.025 for whole-body BMC, and P = 0.04 for whole-body aBMD. Line = median; box = 25%–75%; bars = 5th to 95th. aBMD, areal bone mineral density; BMC, bone mineral content; BMD, bone mineral density.