High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis

Introduction The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved in bone formation such as Wnt proteins and their antagonists probably drive syndesmophyte formation in AS. Methods This study investigated sequential serum levels of functional dickkopf-1 (Dkk1), a potent Wnt antagonist involved in bone formation in arthritis, by capture ELISA with its receptor LRP6 in 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 levels were then related to structural progression (syndesmophyte formation) as well as sclerostin and C-reactive protein (CRP) levels. Results Functional Dkk1 levels were significantly (p=0.025) higher in patients with no syndesmophyte growth (6.78 +/- 5.48 pg/ml) compared with those with syndesmophyte growth (4.13 +/- 2.10 pg/ml). Dkk1 levels were highly correlated to serum sclerostin levels (r=0.71, 95% CI 0.53 to 0.82; p<0.001) but not to CRP (r=0.15, 95% CI -0.10 to 0.38; p=0.23). Conclusion AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signalling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis. Similar to serum sclerostin levels, the functional Dkk1 level thus emerges as a potential biomarker for structural progression in patients with AS