Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy

Abstract

(1) To compare the serum levels of Dickkopf-1 (DKK-1) and bone biomarkers in patients with ankylosing spondylitis (AS) and healthy controls. (2) To examine the effects of anti-tumor necrosis factor-alpha (TNF-alpha) therapy for 3 months on bone biomarkers in patients with AS. We measured the levels of DKK-1, osteocalcin, osteoprotegerin, and C-terminal telopeptide of type I collagen (CTX-1) in patients with AS and in healthy controls at baseline and 3 months after initiating anti-TNF-alpha therapy in AS patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were also measured before and after anti-TNF-alpha therapy in AS patients. Serum levels of DKK-1 were significantly lower in the AS patients than in the controls (P < 0.0001). Osteocalcin and osteoprotegerin levels were significantly higher in the AS patients than in the controls (P < 0.0001). Serum levels of DKK-1 were not changed after the 3-month anti-TNF-alpha therapy. Osteocalcin level increased (P < 0.0001), osteoprotegerin level and BASDAI scores decreased (P = 0.025 and P < 0.0001, respectively) significantly after the 3-months anti-TNF-alpha therapy. Serum DKK-1 level was lower in patients with AS than in healthy controls and did not change after 3 months of anti-TNF-alpha therapy in the AS patients despite the marked improvement in BASDAI scores. These findings suggest the low serum DKK-1 level is related to the pathogenesis of new bone formation in AS, which is resistant to TNF-alpha blocking therapy.