Bone demineralization in adult thalassaemic patients : contribution of GH and IGF-I at different skeletal sites

Background and objective: GH and IGF-I exert an important role in the control of bone formation, as shown by decreased bone mineral density and increased fracture risk in adult hypopituitary patients untreated for GH deficiency (GHD). Different degrees of bone demineralization are frequently reported in patients affected by β-thalassaemia. Considering the high prevalence of GHD recently observed by our group among adult thalassaemic patients, we elected to study the possible role of GH-IGF-I abnormalities in the pathogenesis of the osteopenia/osteoporosis of this disease. Design: Sixty-four adult thalassaemic patients (49 with thalassaemia major and 15 with thalassaemia intermedia, 23 men and 41 women, aged 31.4 ± 6.8 years) were studied. Methods: Bone mineral density was assessed by dual energy X-ray absorptiometry at lumbar spine in 62 patients and at proximal femur in 58. All patients underwent GHRH (1 μg/kg as an i.v. bolus) plus arginine (0.5 g/kg as a 30-min i.v. infusion) testing. Severe GHD was defined by GH peaks < 9 μg/l, whereas partial GHD was defined by GH peaks ranging from 9 to 16.5 μg/l. Blood samples for IGF-I measurement were collected. Results: Lumbar osteoporosis and osteopenia were demonstrated in 46/62 (74.1%) and 14/62 (22.5%) patients, respectively. Femoral osteoporosis and osteopenia were documented in 22/58 (37.9%) and 32/58 (55.1%) patients, respectively. Severe GHD was demonstrated in 16/64 patients (25%), while 11 additional patients (17.1%) displayed partial GHD. IGF-I standard deviation score (SDS) was low, that is, below -1.88, in the majority (54.6%) of patients. Lumbar T-score values were not correlated with either GH peaks or IGF-I SDS values. Femoral T-score values were positively correlated with GH peaks (r = 0.38, P < 0.005) and IGF-I SDS values (r = 0.39, P < 0.005). Multiple regression analysis pointed to both GH peak and IGF-I SDS as predictors of femoral T-score. Furthermore, mean femoral T-score was significantly lower in patients with severe GHD than in those with normal GH secretion (-2.94 ± 0.25 vs. -2.15 ± 0.12, P < 0.01). Conclusion: This study, while confirming the high prevalence of both osteopenia/osteoporosis and somatotropin-somatomedin deficiency in adult thalassaemic patients, indicates that defective GH secretion and diminished serum IGF-I levels may contribute to femoral demineralization in these patients. Further studies are worth carrying out to evaluate the efficacy of biosynthetic GH administration on bone abnormalities of GH-deficient thalassaemic adults