Author/Authors :
Refaat, Samar M. Ain Shams University - Faculty of Medicine - Department of Internal Medicine, Egypt , Moussa, Mohamed M. Ain Shams University - Faculty of Medicine - Department of Internal Medicine, Egypt , Alhagrassy, Rehab S. Ain Shams University - Faculty of Medicine - Department of Internal Medicine, Egypt , Heiba, Nihal M Ain Shams University - Faculty of Medicine - Department of Clinical Pathology, Egypt
Abstract :
Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and receptor activator of the NF-KB ligand (RANKL) have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. We measured, in 28 thalassemic patients and in 14 healthy age-, height- and weight-matched control subjects, serum OPG and RANKL levels, and determined their correlations with age (years), the duration of interval between the onset of transfusions and chelation therapy, bone mineral density (BMD), sex steroid levels, serum ferritin, and hemoglobin. Thalassemics displayed lower BMD values than controls both at the lumbar and femoral levels. As far as the OPG/RANKL system is concerned, thalassemic patients had significantly lower levels of OPG compared with controls (90.49 ±86.42 pg/L vs. 40.71 +21.55 pg/L, respectively; p 0.05) and higher, albeit not statistically significant, serum levels of RANKL (257.79+105.050 pg/L vs149.79 ±32.79 pg/L, respectively; p 0.05). RANKL correlated negatively with age (r = -0.3, p 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, p 0.001) Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients. The OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, and may represent changes in the BMD of these patients. Furthermore, these data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis.
