LOW SCLEROSTIN LEVELS: A PREDICTIVE MARKER OF PERSISTENT INFLAMMATION IN ANKYLOSING SPONDYLITIS DURING ANTI-TNF THERAPY?

Abstract

Introduction: Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-TNF therapy. Aim: The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy. Material and Methods: Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients’ sclerostin levels, sclerostin binding LRP6 and BMD were evaluated at the same time points and compared to controls. Results: At baseline, AS patients had lower sclerostin levels [60.5 (32.7) vs. 96.7 (52.9) pmol/l, p=0.002] and comparable sclerostin binding to LRP6 (p=0.387) than controls. Improvement of BASDAI, BASFI, BASMI, ASQoL was observed at baseline vs. 6 vs. 12 months (p<0.01). Concomitantly, a gradual increase in spine BMD (p<0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r=0.468, p<0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (p<0.01). Sclerostin levels progressively increased (baseline vs. 6 vs. 12 months, p<0.001). At 12 months, the sclerostin levels remained significantly lower in patients compared to controls [72.7 (32.3) vs. 96.70 (52.85) pmol/l, p=0.038]. Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high CRP (≥5mg/l) compared to the other 20 patients with normal CRP (p=0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (p=0.023). Conclusion: Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.