Effects of 12 months rec-GH therapy on bone and collagen turnover and bonemineral density in GH deficient children with thalassaemia major

Children suffering from thalassaemia major are reported to have growth dela y and bone alterations even when well transfused and chelated. In the prese nt study we evaluated bone and collagen turnover (bone Gla-protein, BGP; ca rboxyterminal telopeptide of type I collagen, ICTP; aminoterminal propeptid e of type III procollagen, PIIINP, respectively) and bone mineral density ( BMD) in 5 pre-pubertal GH deficient thalassaemic children before and during rec-GH treatment (0.6 IU/kg/week). Data were compared with those recorded in an age- and sex-matched control group. Before treatment, serum BGP and I CTP levels were significantly lower (p<0.0001) in children with thalassaemi a (9.3+/-0.7 ng/ml and 5.3+/-0.5 ng/ml, respectively) than in healthy contr ols (18.9+/-0.9 ng/ml and 14.4+/-0.6 ng/ml, respectively), while serum PIII NP levels did not significantly differ in the two groups (6.7+/-0.7 ng/ml v s 6.7+/-0.7 ng/ml). Mean lumbar BMD values of patients (0.62+/-0.05 g/cm(2) ) were significantly lower (p<0.05) than those recorded in healthy controls (0.78+/-0.01 g/cm2), while femoral BMD values were similar in the two grou ps (patients: 0.70+/-0.08 g/cm(2) vs controls: 0.74+/-0.01 g/cm2). One-year GH therapy significantly increased height velocity (from 2.3+/-0.2 cm/year to 6.1+/-0.4 cm/yr, p<0.0001) and IGF-I levers (from 61.6+/-15.4 to 342+/- 38.5 ng/ml, p<0.005). Serum BGP (basal: 9.3+/-0.7 ng/ml 6(th) month: 10.8+/ -0.6 ng/ml, 12(th) month: 14.9+/-1.4 ng/ml), ICTP (basal: 5.3+/-0.5 ng/ml, 6(th) month: 7.9+/-0.8 ng/ml, 12(th) month: 10.9+/-1.7 ng/ml) and PIIINP le vels (basal: 6.7+/-0.7 ng/ml, 6(th) month: 9.9+/-1.0 ng/ml, 12th month: 9.6 +/-1.4 ng/ml) significantly increased (p<0.05), while no significant effect s were observed on lumbar and femoral BMD values. Although the GH-induced s timulation of bone turnover markedly increased BGP (+60%) and ICTP (+105%) levels, one-year GH therapy was not sufficient to completely normalize thes e parameters, which remained significantly lower than in healthy controls. In conclusion, our study shows that pre-pubertal GH deficient children with thalassaemia major have reduced bone turnover (both bone formation and res orption) and lumbar BMD values, thus indicating that bone metabolism should be monitored and improved even in well-transfused patients. One-year GH tr eatment is able to increase, but not normalize, bone turnover, this effect being insufficient to improve BMD values. More prolonged periods of GH ther apy are probably requested to positively affect both bone turnover and BMD values in GH deficient thalassaemic patients, as occurs in children and adu lts with GH deficiency. (C) 2000, Editrice Kurtis.