Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapyReport as inadecuate




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Arthritis Research and Therapy

, 14:R216

First Online: 12 October 2012Received: 14 August 2012Revised: 03 September 2012Accepted: 12 September 2012

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.

AbbreviationsANOVAanalysis of variance

ASankylosing spondylitis

ASQoLAnkylosing Spondylitis quality of life questionnaire

BASDAIBath Ankylosing Spondylitis Disease Activity Index

BASFIBath Ankylosing Spondylitis Functional Index

BASMIBath Ankylosing Spondylitis Metrology Index

BMDbone mineral density

CVcoefficient of variation

CRPC-reactive protein

DXAdual-energy X-ray absorptiometry

ELISAenzyme-linked immunosorbent assay

ESRerythrocyte sedimentation rate

FSHserum follicle stimulating hormone

ISCDInternational Society for Clinical Densitometry

LRP6low-density lipoprotein receptor-related protein 6

MMP-3matrix metalloproteinase 3

mSASSSmodified Stoke Ankylosing Spondylitis Spine Score

NSAIDsnon-steroidal anti-inflammatory drugs

OD450optical density

TNFtumor necrosis factor

Wntwingless.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4055 contains supplementary material, which is available to authorized users.

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