Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Predictive and Protective Value of Biomarkers in Patients with Ankylosing Spondylitis Who Are At High Risk of Radiographic Spinal Progression.

Poddubnyy1,  Denis, Conrad2,  Kristina, Ruiz-Heiland3,  Gisela, Syrbe2,  Uta, Haibel2,  Hildrun, Appel2,  Heiner, Rudwaleit4,  Martin

Charité Medical University, Campus Benjamin Franklin, Berlin, Germany
Charité– Campus Benjamin Franklin, Berlin, Germany
University of Erlangen-Nuremberg, Erlangen, Germany
Ev. Krankenhaus Hagen-Haspe, Hagen, Germany

Background/Purpose:

In the recent years several biomarkers have been found to be associated with radiographic spinal progression/syndesmophyte formation in ankylosing spondylitis (AS): matrix metalloproteinase 3 (MMP-3) and C-reactive protein (C-RP) (positive association), sclerostin (SOST), Dickkopf 1 (DKK1), and periostin, (negative association). However, it is not clear, whether these biomarkers are also able to predict new bone formation in AS patients who are at high risk of radiographic progression due to a presence of syndesmophytes at baseline. The objective of the study was to to investigate the association of biomarkers with radiographic progression (new syndesmophytes formation or growth of the existing syndesmophytes) in patients with AS with and without radiographic damage at baseline.

Methods:

Altogether 97 patients with AS from the German Spondyloarthritis Inception Cohort (GESPIC) were included in this analysis. Radiographs of the lumbar and cervical spine performed at baseline and after 2 years of follow-up were scored independently by two trained readers according to the mSASSS scoring system. Three groups of patients were defined according to the scoring results:

Group I (n=26): patients with syndesmophytes at baseline and new syndesmophyte or syndesmophytes growth after 2 years;

Group II (n=38): patients with syndesmophytes at baseline but without radiographic progression after 2 years;

Group III (n=33): patients without radiographic spinal damage at baseline and after 2 years.

Serum levels of the following biomarkers were examined: MMP-3, CRP, SOST, DKK1, periostin, C-terminal cross-linked telopeptide of type II collagen (CTX-II), bone alkaline phosphatase, sRANKL, osteoprotegerin, N-terminal telopeptide of type I collagen, procollagen type I and II N-propeptide (PINP and PIINP), bone sialoprotein and cartilage oligomeric matrix protein.

Results:

There was a statistically significant difference between Group I and Group II in the serum levels of MMP3, CRP and PIINP (table), indicating that higher serum levels of these biomarkers might be associated with active progression of spinal structural changes in the patients who are at high risk of such a progression. At the same time, higher levels of SOST, DKK-1, periostin, and CTX-II might be protective regarding radiographic spinal progression in AS since the highest level of these markers were found in patients without syndesmophytes neither at baseline nor after two years despite high levels of CRP, MMP3 and PIINP (table). None of the other investigated biomarkers showed an association with radiographic spinal progression.

Table. Baseline serum levels of biomarkers in three groups of patients AS defined according to the presence of syndesmophytes and their progression over 2 years.

BiomarkersGroup I: baseline syndesmophytes, progressionGroup II: baseline syndesmophytes, no progressionGroup III: no syndesmophytes, no progressionp (Kruskall-Wallis test)
MMP-3, ng/ml30.3 ± 25.9*14.4 ± 19.725.5 ± 34.20.020
CRP, mg/l17.1 ± 17.1*8.7 ± 9.911.7 ± 22.80.152
PIINP, ng/ml175.4 ± 81.6*133.5 ± 82.5233.3 ± 237.70.099
CTX-II, ng/ml1259 ± 10822464 ± 30787170 ± 11097*§0.002
SOST, ng/ml0.15 ± 0.40.8 ± 2.43.5 ± 6.3*§0.002
DKK-1, ng/ml4.7 ± 2.15.4 ± 5.39.8 ± 6.9*§0.038
Periostin, ng/ml46.3 ± 78.5106.8 ± 151.8243.7 ± 201.2*§<0.001
* p < 0.05 vs. Group II;§p < 0.05 vs.Group I.

Conclusion:

Higher levels of MMP-3, CRP and PINP may predict further radiographic spinal progression/new bone formation in patients with AS already having syndesmophytes, while higher levels of SOST, DKK-1, periostin and CTX-II might play a protective role.

To cite this abstract, please use the following information:
Poddubnyy, Denis, Conrad, Kristina, Ruiz-Heiland, Gisela, Syrbe, Uta, Haibel, Hildrun, Appel, Heiner, et al; Predictive and Protective Value of Biomarkers in Patients with Ankylosing Spondylitis Who Are At High Risk of Radiographic Spinal Progression. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1338
DOI:

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