title: Iron chelation therapy in Upper Egyptian transfusion-dependent pediatric homozygous beta-thalassemia major: impact on serum L-carnitine/free fatty acids, osteoprotegerin/the soluble receptor activator of nuclear factor-kappabeta ligand systems, and bone mineral density.
abstract: Bone disease in beta-thalassemia major (betaTM) remains poorly understood. Receptor activator of nuclear factor-kappabeta ligand (RANKL) regulates osteoclast formation and function. RANKL activity is balanced by interaction with its receptor (RANK) and binding to osteoprotegerin (OPG). L-Carnitine (LC) enhances osteoblastic activity by furnishing fuel. This study hypothesized that abnormal bone metabolism in betaTM involves imbalanced RANKL/OPG and LC/free fatty acids (FFAs) metabolism. Sixty-nine transfusion-dependent betaTM patients and 15 healthy controls were enrolled. One group of patients (n=34) received desferrioxamine (DFO) and the other (n=35) did not. Serum OPG, soluble RANKL (sRANKL), FFAs, LC [total LC (TC), free LC (FC), and esterified LC (EC)], calcium, and inorganic phosphate were measured by specific immuno and colorimetric assays; bone mineral density was examined by dual x-ray absorptiometry. Patients showed lower levels of OPG, TC, FC, EC and higher levels of sRANKL, sRANKL/OPG ratio, and FFAs than controls. Patients on DFO showed lower levels of OPG, TC, FC and higher levels of sRANKL, sRANKL/OPG ratio, and FFAs than those without chelation. In patients, sRANKL correlated negatively with TC and OPG and FC correlated positively with OPG and negatively with sRANKL, sRANKL/OPG ratio, and FFAs. In conclusion, altered bone metabolism owing to imbalanced osteoclastic bone resorption versus constructive osteoblastic activities in betaTM pediatric patients could be due to abnormal sRANKL-OPG and LC-FFAs systems that were worsened by DFO.
authors.affiliation: Department of Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt. eah3a2003@yahoo.com
authors.forename: Enas A
authors.initials: EA
authors.lastname: Hamed
authors.forename: Nagwa A
authors.initials: NA
authors.lastname: Mohamed
authors.forename: Tarek H
authors.initials: TH
authors.lastname: El-Metwally
authors.forename: Manal M
authors.initials: MM
authors.lastname: Kamal
mesh_terms: D001803:Blood Transfusion; D015519:Bone Density; D002331:Carnitine / Q000097:blood*; D016022:Case-Control Studies; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D003676:Deferoxamine / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D017262:Siderophores / Q000627:therapeutic use; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D005230:Fatty Acids, Nonesterified; D053244:Osteoprotegerin; D053245:RANK Ligand; D017262:Siderophores; D003676:Deferoxamine; D002331:Carnitine