Background Ankylosing spondylitis (AS) is associated with both pathologic formation of new bone and enhanced bone resorption.
Objectives The objectives of this study were to assess a panel of biomarkers reflecting bone turnover and to determine their relationship with syndesmophyte formation, bone mineral density (BMD) and disease activity in AS.
Methods All patients at the study centres fulfilling the modified New York criteria of AS were invited to participate. Exclusion criteria were psoriasis and inflammatory bowel disease. Spinal mobility was assessed for calculation of BASMI and the patients answered questionnaires. BASDAI, ASDAS and CRP were chosen as disease activity parameters. Lateral spine radiographs were scored for syndesmophyte formation (mSASSS). BMD was measured with dual energy x-ray absorptiometry (DXA). Levels of biomarkers were measured with sandwich enzyme-linked immunosorbent assays (ELISA) in patient sera and compared with levels of healthy blood donor controls. The biomarkers studied were: Wingless proteins (Wnt3a, Wnt5a), Dickkopf-1 (Dkk-1), sclerostin, soluble receptor activator of nuclear factors-κB ligand (sRANKL) and osteoprotegerin (OPG)
Results 204 patients (57% men) with a mean age of 50±13 years and disease duration 15±11 years and 80 age and sex matched controls were included.
The AS patients had significantly higher levels of Wnt3a (3.72±0.99 vs. 2.88±0.84 ng/mL; p<0.001) and lower levels of sclerostin (35.33±21.54 vs. 38.33±13.96 pmol/L; p=0.014) compared with the controls. Wnt3a was positively correlated with BASMI (rS=0.219; p=0.002) and mSASSS (rS=0.196; p=0.005) but negatively correlated with BMD femoral neck (rS=-0.160; p=0.023). High CRP was significantly correlated with lower levels of sclerostin (rS=-0.208, p=0.003) and Dkk-1 (rS=-0.140, p=0.045).
Age (rS=0.389; p<0.001) and male sex (rS=0.377; p<0.001) and low femoral neck BMD (rS=-0.187; p=0.008) were significantly correlated with increasing mSASSS. After adjusting for age and sex in multiple linear regression high Wnt3a (B=2.71; p=0.017) and low Dkk-1 (B=-0.002; p=0.025) remained independently associated with increasing mSASSS (R2=0.333). Low sclerostin (B=0.012; p<0.001) and high mSASSS (B=-0.010; p=0.003) were independently associated with low Z-score for BMD femoral neck (R2=0.091).
Conclusions The understanding of bone biomarkers in AS is challenged by the two enhanced opposite bone remodelling processes of the disease. The results of this study indicates that elevated Wnt3a could be a marker for syndesmophyte formation in AS.
Disclosure of Interest None Declared
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