Effect of tumour necrosis factor-α inhibitor on serum level of dickkopf-1 protein and bone morphogenetic protein-7 in ankylosing spondylitis patients with high disease activity.
OBJECTIVE
To examine changes in serum levels of the bone remodelling molecules dickkopf-1 (Dkk-1), sclerostin, wingless-type protein-3a (Wnt-3a), and bone morphogenetic protein-7 (BMP-7) during 6 months of anti-tumour necrosis factor (anti-TNF) treatment in ankylosing spondylitis (AS) patients with high disease activity.


METHODS
We included 40 patients with axial AS: 20 patients with high disease activity were assigned to treatment with TNF inhibitor and 20 with low disease activity were assigned to non-steroidal anti-inflammatory drug (NSAID) treatment. Markers of bone remodelling and inflammation were assessed at baseline and after 6 months.


RESULTS
In the TNF inhibitor-treated group Dkk-1 decreased significantly from 196.8 pg/mL [95% confidence interval (CI) 94.1-399.0] to 116.3 pg/mL (95% CI 38.0-301.6) and BMP-7 increased significantly from 1.4 pg/mL (95% CI 0-23.0) to 20.3 pg/mL (95% CI 4.9-41.3). There was a significant negative correlation between Dkk-1 and BMP-7 at 6 months (r = -0.64, p = 0.004) in this group. Non-parametric regression analysis adjusted for disease duration, age, sex, baseline modified Stoke's Ankylosing Spondylitis Spine Score (mSASSS), and baseline C-reactive protein (CRP) confirmed a statistically significant effect of treatment on time-related changes of Dkk-1 and BMP-7. Erythrocyte sedimentation rate (ESR), CRP, and also the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreased significantly in the anti-TNF-treated group.


CONCLUSIONS
Among the potential biomarkers of bone remodelling in AS, Dkk-1 and BMP-7 displayed significant time alterations and correlative interactions during anti-TNF treatment.
Division of Rheumatology, Department of Internal Medicine and Gerontology, Jagiellonian University Medical College , Krakow , Poland.
M
M
Korkosz
J
J
Gąsowski
P
P
Leszczyński
K
K
Pawlak-Buś
S
S
Jeka
M
M
Siedlar
T
T
Grodzicki
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055419:Bone Morphogenetic Protein 7 / Q000097:blood*; D019485:Bone Morphogenetic Proteins / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D060509:Wnt3A Protein / Q000097:blood
D048868:Adaptor Proteins, Signal Transducing; D018501:Antirheumatic Agents; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human; D014409:Tumor Necrosis Factor-alpha; D060509:Wnt3A Protein