Abstract: Objectives: Osteoprotegerin (OPG) has been associated with increased risk and severity of atherosclerotic disease in the general population. Since ankylosing spondylitis (AS) is a chronic inflammatory disease associated with accelerated atherosclerosis, we aimed to assess whether OPG levels correlate with disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of endothelial cell activation in patients with AS undergoing TNF-a antagonist therapy. Methods: We assessed OPG plasma concentration in 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-a antagonist-infliximab therapy. OPG levels were measured immediately before and after an infliximab infusion. Correlations of OPG levels with disease activity, clinical characteristics, systemic inflammation, metabolic syndrome features, adipokines and biomarkers of endothelial activation were assessed. Changes in OPG concentration following an infusion of anti-TNF-a monoclonal antibody-infliximab were also analysed. Results: We found a positive correlation between OPG levels and markers of disease activity such as BASDAI and VAS spinal pain (r=0.497, p=0.01; r=0.390; p=0.04, respectively). No differences in OPG levels according to specific clinical features of the disease were seen. An inverse correlation between OPG levels and total cholesterol and LDL-cholesterol was also found (r=-0.451; p=0.02 and r=-0.411; p=0.03, respectively). A correlation between OPG and asymmetric dimethylarginine, a biomarker of endothelial cell activation, was also disclosed (r=0.533; p=0.01). No correlation between OPG level and insulin resistance was observed. An infliximab infusion did not lead to a significant reduction in OPG levels. Conclusions: OPG shows a correlation with markers of disease activity and endothelial activation in non-diabetic ankylosing spondylitis patients undergoing TNF-a antagonist therapy

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