title: Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major.
abstract: Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41 years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with beta-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/- 0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-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). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in beta-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.
authors.affiliation: Division of Endocrinology and Metabolism, Hippocrateion Hospital of Athens, 108 Vassilisis Sofias Avenue, 11527, Athens, Greece. drangelnick@hotmail.com
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Angelopoulos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Goula
authors.forename: Eugenia
authors.initials: E
authors.lastname: Katounda
authors.forename: Grigorios
authors.initials: G
authors.lastname: Rombopoulos
authors.forename: Victoria
authors.initials: V
authors.lastname: Kaltzidou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kaltsas
authors.forename: Sophia
authors.initials: S
authors.lastname: Malaktari
authors.forename: Vassilis
authors.initials: V
authors.lastname: Athanasiou
authors.forename: George
authors.initials: G
authors.lastname: Tolis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000150:complications*; D053244:Osteoprotegerin / Q000097:blood* / Q000502:physiology; D053245:RANK Ligand / Q000097:blood; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood* / Q000502:physiology; D017086:beta-Thalassemia / Q000097:blood* / Q000150:complications
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505688:TNFSF11 protein, human