Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Abstract

IntroductionSclerostin 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-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.MethodsThirty 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 low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.ResultsAt 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 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (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 (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, 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 C reactive protein (CRP) (≥ 5 mg/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). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.ConclusionsPersistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.

Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis

“…Of particular note, low serum sclerostin levels in patients with AS in this study were significantly associated with the formation of new syndesmophytes. Similar findings were seen in two other cohorts of Swedish [50] and Brazilian AS patients [64]. Yet, other studies showed no differences or even demonstrated elevated levels of sclerostin comparing between AS patients and controls [46, 65, 66].…”

Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis

“…There are reports correlating AS and decreased SOST levels 5 24. AS patients have minimal expression of SOST in osteocytes 5.…”

The ASAS Criteria for Axial Spondyloarthritis: Strengths, Weaknesses, and Proposals for a Way Forward

“…(Hamlet, William Shakespeare). [39,40] • Proteonomics [43] • Specific Biomarkers Vascular endothelium growth factor [44] Matrix metalloproteinase-3 [45,46] Sclerostin [47,48] Calprotectin [49] Citrullinated vimentin [50] Dikkopf-1 [51] Anti-CD74 antibodies [52][53][54] 56.•• van Tubergen A. The changing clinical picture and epidemiology of spondyloarthritis.…”

“…Appropriate assessment of criterion validity of the Bconstruct^axSpA would include verification of its biologic association with AS genetics, including MHC and non-MHC gene variants, and proteomic or other biomarkers that turn out to be typical for and occur frequently in classical AS. Candidate biomarkers, mostly hypothetical at this stage, are listed in Table 6 [39,40,[43][44][45][46][47][48][49][50][51][52][53][54]. Some of these biomarkers may turn out to have prognostic value, and those will be most suitable as predictors of outcome, not as candidates for classification criteria that are intended to create homogeneity, not prognostication.…”