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


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 low-density lipoprotein receptor-related protein 6 (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 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.


CONCLUSIONS
Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.
Carla G S
CG
Saad
Ana C M
AC
Ribeiro
Julio C B
JC
Moraes
Liliam
L
Takayama
Celio R
CR
Goncalves
Marcelo B
MB
Rodrigues
Ricardo M
RM
de Oliveira
Clovis A
CA
Silva
Eloisa
E
Bonfa
Rosa M R
RM
Pereira
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016015:Logistic Models; D008137:Longitudinal Studies; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D048868:Adaptor Proteins, Signal Transducing; D018501:Antirheumatic Agents; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C422903:SOST protein, human; D014409:Tumor Necrosis Factor-alpha