Bone Abstracts

Poor bone mineralization remains a major health problem in patients with Thal and has been linked to functional zinc deficiency despite adequate dietary intake. The global etiology of poor bone mineralization includes inadequate dietary intake of calcium and vitamin D, endocrinopathies leading to disturbed calcium homeostasis, dysregulation of the GH–IGF1 axis, and delayed puberty, all resulting in limited growth, decreased bone formation and increased bone resorption. These effects are further aggravated by chronic blood transfusions and chelation therapy, which are indispensable for survival. The aim of this study was to ascertain whether zinc supplementation leads to improved bone mineralization in adolescents and adults with Thal. 42 subjects (21 females, 10–30 years) with Thal and low bone mass were randomly assigned to receive 25 g zinc/day or placebo; 33 completed the study (16.9±5.1 years, mean±S.D.), 81% were transfusion dependent. Bone mineral content (BMC) and bone mineral areal density (aBMD) were assessed by dual energy X-ray absorptiometry. Dietary intake was assessed by food frequency questionnaire at 0, 12 and 18 months. Fasting blood was assessed for plasma zinc and copper at 0, 3, 6, 12 and 18 months. Plasma zinc was depressed (≤70 μg/dl) in 11 subjects (26%) at baseline and increased significantly with zinc supplementation (P=0.014). Zinc intake at baseline averaged 123±66% of US dietary recommendations. Using intention to treat analysis, and mixed effects linear modeling controlling for baseline, the zinc group (n=24) had significantly greater relative increases in whole body BMC (3.2%, P=0.027) and whole body aBMD (2.3%, P=0.046) compared to placebo after 18 months. Zinc-supplemented adults (n=15) had significantly greater relative increase in spine BMC (P=0.03), spine aBMD (P=0.039), whole body BMC (P=0.046) and whole body aBMD (P=0.019) compared to placebo. No significant change was observed in any of the bone variables in the adolescent subjects taking zinc, likely due to the increased variability and smaller sample size. These results suggest that Thal patients suffer a functional zinc deficiency which limits bone mineralization. This nutritional supplement was well-tolerated and merits further investigation in larger trials across a broader range of age and disease severity.