DKK-1 LEVELS Are DECREASED IN PATIENTS with Ankylosing Spondylitis and NOT Influenced by Anti-TNF Therapy

초록

Background: Signaling through the Wnt pathway leads to new bone formation, whilst DKK-1 is a Wnt antagonist. Preliminary data in patients with ankylosing spondylitis (AS) shows that levels of DKK-1 are low in patients with AS than in healthy controls suggesting that this might account for the propensity to new bone formation in AS. Purpose: 1. To compare DKK-1 levels and other bone biomarkers in patients with AS compared to controls. 2. To examine the effects of anti-tumor necrosis factor (TNF) therapy for 3 months on DKK-1 levels and other bone biomarkers in AS. Method: We studied 56 patients with AS (47 males, age 35.1 ± 9.6 years, disease duration 6.9 ± 4.8 years, BASDAI 7.7 ± 1.9, CRP 1.7 ± 2.0 mg/dl, mean ± SD), and 40 controls (31 male, age 43.5 ± 8.6 years). We also assessed DKK-1 in 49 AS patients and 39 healthy controls at baseline and 3 months after initiating anti-TNF therapy in AS patients (etanercept = 6, infliximab = 22, adalimumab = 21). DKK-1 was assayed by ELISA. We evaluated biomarkers of bone formation (osteocalcin, osteoprotegerin) and resorption (C-terminal telopeptide of type I collagen, CTX-1) by ELISA. Results: Serum DKK-1 (12320.6 ± 6136.8 pg/ml) levels were significantly lower in AS than in controls (20811.1 ± 6136.8 pg/ml) (p<0.0001). Serum osteocalcin (14.5 ± 5.6 ng/ml), osteoprotegerin (3.5 ± 1.1 pmol/L) levels were significantly higher in AS than in controls (osteocalcin 8.9 ± 3.4 ng/ml, osteoprotegerin 2.03 ± 1.04 pmol/L, p<0.0001 respectively). Mean serum CTX-1 levels were not significantly different between AS and controls. Serum DKK-1 and CTX-1 levels were not changed 3 months after treatment with anti-TNF. Conclusion: In accordance with a previous report, we show decreased DKK-1 in AS than healthy controls. DKK-1 levels are not influenced by anti-TNF therapy for 3 months. Our data does support a role for DKK-1 and Wnt interaction in the pathogenesis of new bone formation in AS.