Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis.

OBJECTIVE

To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, back mobility, osteoproliferation, and bone mineral density (BMD).

METHODS

Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-energy x-ray absorptiometry.

RESULTS

Two hundred four patients with AS (NY criteria; 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 patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (r(S) = -0.21, p = 0.003) and DKK-1 (r(S) = -0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age.

CONCLUSION

Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.