BONE-MINERAL DENSITY IN PREPUBERTAL CHILDREN WITH BETA-THALASSEMIA - CORRELATION WITH GROWTH AND HORMONAL DATA

Patients with beta-thalassemia major (beta-thalassemia) frequently hav e bone disorders of multifactorial etiology. We attempted to analyze t he relationship between the bone mineral density ([BMD] measured by du al-photon absorptiometry) and auxanologic parameters, degree of sidero sis, 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 childre n with beta-thalassemia major and 15 age-matched children with constit utional short stature (CSS), who have normal glucose tolerance and thy roid function. Children with beta-thalassemia had a significantly decr eased 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 m u g/L) in 12 of the 30 thalassemic children. Serum concentrations of I L-1 beta and TNF-alpha did not differ among the two study groups. Hypo calcemia was detected in five of the 30 thalassemic patients: hypopara thyroidism was diagnosed in two of the five and rickets in the other t hree. BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, we ight, height, height standard deviation score [HSDS], and body mass in dex [BMI]). It is suggested that increasing the circulating IGF-I conc entration through aggressive nutritional therapy and/or GH/IGF-I thera py with supplementation with vitamin D and/or calcium might improve bo ne growth and mineralization and prevent the development of osteoporos is and consequent fractures in these patients. Such therapy requires b linded controlled trials. Copyright (C) 1998 by W.B. Saunders Company.