The “lively” cytokines network in β-Thalassemia Major-related osteoporosis

Osteoporosis affects approximately 40–50% of adult patients with β-Thalassemia Major (βTM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of βTM-osteoporosis. OPG/RANKL system acts downstream from IL-1α, IL-6 and TNF-α 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 βTM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in βTM patients. IL-1α, IL-6 and TNF-α, 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), 17β-estradiol, and free-testosterone levels were measured in 30 well treated βTM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. βTM 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-1α (P < 0.0001), TNF-α (P < 0.0001) and IL-6 (P < 0.05) were all increased in βTM patients as compared with controls. In βTM patients, IL-1α 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-α 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 βTM-patients, suggesting osteoporosis. their involvement in the pathogenesis of βTM