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

Patients with beta-thalassemia major (beta-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-1 beta [IL-1] and tumor necrosis factor-alpha [TNF-alpha]) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature (CSS), who have normal glucose tolerance and thyroid function. Children with beta-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 mu g/L) in 12 of the 30 thalassemic children. Serum concentrations of IL-1 beta and TNF-alpha 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. Copyright (C) 1998 by W.B. Saunders Company.