Genetic and acquired predisposing factors and treatment of osteoporosis inthalassaemia major

We have previously shown a high incidence of osteopenia and osteoporosis in patients with thalassaemia major. These bone changes were more severe in m ales than females, in those with diabetes mellitus and with hypogonadal-hyp ogonadism, Our recent studies concern the relationship of erythroid activit y, assessed by serum transferrin receptors as an overall measure of anaemia , to osteoporosis. Serum transferrin receptor levels correlated with the me an pre-transfusion haemoglobin level, but there was no correlation with the incidence of osteopenia and osteoporosis. As osteoporosis has a strong gen etic component we have also studied the COLIA1 and COLIA2 genes which code for the major protein of bone (type 1 collagen), Studies by others have sho wn in non-thalassaemic patients that a polymorphism G-->T or TT in a regula tory region of COLIA1 at the recognition site for transcription factor Spl is associated with the presence of osteoporosis. Our studies suggest that S pl polymorphism is not specific to any one ethnic group; the polymorphism o ccurs more commonly in females (female to male ratio 2:1). In male thalassa emia major patients the presence of the Spl mutation was associated with mo re severe osteoporosis of the spine and the hip compared with female patien ts. There is failure of improvement in spinal osteoporosis with bisphosphon ate therapy (intravenous Pamidronate) in male patients with the Spl mutatio n.