New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia.
Osteoporosis represents an important cause of morbidity in adult patients with thalassaemia major (TM). The pathogenesis of osteoporosis in TM is multifactorial, and includes bone marrow expansion, endocrine dysfunction and iron overload. Additional genetic factors, such as the COLIA 1 gene polymorphism, seem to play an important role in the development of low bone mass in these patients. However, the mechanisms through which these factors lead to bone loss have not been completely clarified. The diminished osteoblast function is accompanied by a comparable or even greater increase in osteoclast activity. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway has been recently recognized as the final, dominant mediator of osteoclast proliferation and activation. There is increased evidence that this pathway interferes in the pathogenesis of thalassaemia-induced osteoporosis. Currently, bisphosphonates that are potent inhibitors of osteoclast function have been used in TM patients with encouraging results. This review attempts to summarize all the novel data for the biology of bone damage in TM. It also describes the results of all major studies that have investigated the effects of different treatment modalities for TM-induced osteoporosis, their mode of action, and the future implications of their use.
Voskaridou
Ersi
E
Thalassaemia Centre, Laikon General Hospital, Athens, Greece. ersi_voskaridou@yahoo.com
Terpos
Evangelos
E
D000328:Adult; D024042:Collagen Type I / Q000235:genetics; D004164:Diphosphonates / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D011110:Polymorphism, Genetic; D017086:beta-Thalassemia / Q000150:complications* / Q000188:drug therapy / Q000473:pathology
D024042:Collagen Type I; D004164:Diphosphonates