Bone mineral density in prepubertal children with β-thalassemia: Correlation with growth and hormonal data

Abstract

Patients with β-thalassemia major (β-thalassemia) frequently have bone disorders of multifactorial etiology. We attempted to analyze the relationship between the bone mineral density ([BMD] measured by dual-photon absorptiometry) and auxanologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 (IGFBP3) axis, calcium-phosphate balance, parathyroid hormone (PTH), and cytokines (interleukin-1β [IL-1] and tumor necrosis factor-alpha [TNF-α]) in 30 prepubertal children with β-thalassemia major and 15 age-matched children with constitutional short stature (CSS), who have normal glucose tolerance and thyroid function. Children with β-thalassemia had a significantly decreased BMD and mean BMD% for age and sex (0.75 ± 0.24 g/cm 2 and 71% ± 10%, respectively) versus children with CSS (1.06 ± 0.3 g/cm 2 and 92% ± 7%, respectively). Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 (49 ± 21 ng/mL and 1.2 ± 0.25 mg/L, respectively) compared with control children (153 ± 42 ng/mL and 2.1 ± 0.37 mg/L, respectively). The GH response to provocation by clonidine and glucagon was defective (peak GH < 7 μg/L) in 12 of the 30 thalassemic children. Serum concentrations of IL-1β and TNF-α did not differ among the two study groups. Hypocalcemia was detected in five of the 30 thalassemic patients: hypoparathyroidism was diagnosed in two of the five and rickets in the other three. BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, height standard deviation score [HSDS], and body mass index [BMI]). It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and/or GH/IGF-I therapy with supplementation with vitamin D and/or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients. Such therapy requires blinded controlled trials.