Serum levels of Dkk-1, sclerostin and VEGF in patients with ankylosing spondylitis and their association with smoking, and clinical, inflammatory and radiographic parameters

Objective: To evaluate serum Dickkopf-1 (Dkk-1), sclerostin and vascular endothelial growth factor (VEGF) levels in patients with ankylosing spondylitis (AS) compared to healthy controls as well as their association with smoking, and clinical, inflammatory and radiographic parameters.

Methods: Serum samples for total Dkk-1, sclerostin and VEGF were obtained from 57 tumour necrosis factor (TNF) inhibitor naïve patients with AS and 34 sex-, age- and body mass index (BMI)-matched controls. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), modified Stroke AS Spine Score (mSASSS) and smoking status were assessed for each patient.

Results: There was no significant difference in serum bone metabolism markers between AS patients and controls. Dkk-1 levels were significantly (P<0.05) higher in AS patients with elevated ESR and CRP and no syndesmophytes, and were significantly (P<0.001) correlated with sclerostin levels (r=0.592). VEGF levels were significantly (P<0.05) higher in AS patients with current and ever smoking, elevated ESR and CRP, and high BASDAI and BASFI, and were significantly (P<0.05) correlated with ESR (r=0.284), CRP (r=0.285), BASDAI (r=0.349) and BASFI (r=0.275). In multivariate regression analyses, high Dkk-1 levels were significantly (P≤0.001) associated with elevated ESR and CRP, no syndesmophytes and high sclerostin levels, and high VEGF levels significantly (P<0.05) with ever smoking, and elevated ESR and CRP.

Conclusion: In AS, serum Dkk-1 concentrations appear to be related not only to syndesmophyte formation but also to systemic inflammation. Furthermore, high VEGF levels may be associated with smoking exposure.