The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis.
Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM-patients, suggesting their involvement in the pathogenesis of beta TM-osteoporosis.
Morabito
Nunziata
N
Department of Internal Medicine, University of Messina, Via Consolare Valeria, Messina 98100, Italy. nancynat@libero.it
Russo
Giuseppina T
GT
Gaudio
Agostino
A
Lasco
Antonino
A
Catalano
Antonio
A
Morini
Elisa
E
Franchina
Fabio
F
Maisano
Domenica
D
La Rosa
Mariangela
M
Plota
Maria
M
Crifò
Adolfa
A
Meo
Anna
A
Frisina
Nicola
N
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D001862:Bone Resorption; D001842:Bone and Bones / Q000502:physiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000652:urine; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications* / Q000652:urine
D015415:Biomarkers; D016207:Cytokines