Osteoporosis in beta-thalassaemia major patients: analysis of the genetic background

Regular blood transfusions from infancy until adulthood in beta -thalassaem ia major patients have substituted severe bone deformities with less marked skeletal lesions as osteoporosis. Osteoporosis is characterized by low bon e mass and disruption of bone architecture, resulting in reduced bone stren gth and increased risk of fractures. Genetic factors have an important role in determining bone mineral density (BMD). We have investigated the possib le association between BMD and two polymorphisms in 135 beta -thalassaemic patients: (i) a substitution G --> T in a regulatory region of the COLIA1 g ene encoding for the major protein of bone (type 1 collagen), and (ii) a on e-base deletion in intron 4 (713-8del C) of transforming growth factor beta 1 (TGF-beta1) gene. We have found a remarkable incidence (90%) of osteopen ia and osteoporosis among regularly transfused patients. Bone mass was lowe r in men than in women (P = 0.0023), with a more prevalent osteopenia/osteo porosis of the spine in men than in women (P = 0.001). The sample was strat ified on the basis of BMD expressed as Z-score, i.e. normal, osteopenic and osteoporotic patients, and genotype frequencies of each group were evaluat ed. TGF-beta1 polymorphism failed to demonstrate a statistical difference i n BMD groups. However, subjects with heterozygous or homozygous polymorphis m of the COLIA1 gene showed a lower BMD than subjects without the sequence variation (P = 0.012). The differences among genotypes were still present w hen the BMD was analysed as adjusted Z-score and when men and women were an alysed separately (P = 0.022 and 0.004 respectively), with men more severel y affected. Analysis of COLIA1 polymorphism could help to identify those th alassaemic patients at risk of osteoporosis and fractures.