Background/Purpose:

Dickkopf-1 (DKK-1) and sclerostin (SOST) are 2 inhibitory proteins of the Wnt signalling pathway that could rationally be involved either in AS osteoporosis or in the osteoblastogenesis associated with syndesmophyte construction. We aimed to investigate serum levels of DKK-1 among patients with recent inflammatory back pain fulfilling ASAS criteria for spondyloarthritis (SpA) and to investigate the parameters associated or correlated with DKK-1and SOST serum levels.

Methods:

The DESIR cohort is a prospective, multicenter French cohort of patients with early IBP (Calin or Berlin criteria) (>3 months and <3 years of duration) suggestive of SpA, including 708 patients. DKK-1 and SOST serum levels were assessed at baseline on the whole cohort by sandwich ELISA (Biomedica, Vienna). DDK-1 and SOST serum levels were further analyzed in the subgroup of patients fulfilling ASAS criteria for SpA (N=479; 68.9%) and compared with serum levels from 71 controls (without autoimmune or chronic inflammatory disease). 461 SpA patients (94.8%) were treated with NSAIDs, 62 with corticosteroids (less than 10 mg per day) and 67 with DMARDs (35 SSZ and 32 MTX) at inclusion in the study. All SpA patients were naive of any TNF blocker at inclusion in the study. Univariate and multivariate analyses were performed in order to identify the main predictors of DKK-1 and SOST serum levels in SpA patients.

Results:

Serum DKK-1 levels were available for 695 patients with IBP (472 of them fulfilling ASAS criteria for axial SpA) and were significantly increased in SpA patients (mean ± SEM 30.7 ± 0.7 pmol/L) compared with controls (10.8 ± 1.1 pmol/L) (p<0.0001). DKK-1 serum levels were significantly correlated with ESR (P=0.04; r=0.10), CRP (P=0.015; r=0.11), ASDAS-ESR (P=0.03; r=0.10), ASDAS-CRP (P=0.016; r=0.11). A significant positive correlation between DKK-1 serum levels and lumbar spine BMD was observed (P=0.04; r=0.13). DKK-1 serum levels were significantly higher among SpA patients with syndesmophytes (mSASSS>0; N=131) (mean ± SEM 35.4 ± 1.6 pmol/L) compared with patients with normal X-Rays (N=334) (mean ± SEM 28.6 ± 1.1 pmol/L) (P<0.0001). Multivariate analysis led to a significant association of DKK-1 serum levels with the presence of syndesmophytes at baseline. SOST was not significantly increased among SpA patients compared with controls. SOST serum levels were significantly correlated with US CRP (r=-0.20; P<0.0001), DKK-1(r=0.13; P<0.006), and age (r=0.31; P<0.0001). Neither axial structural lesions nor BMD measurements were associated or correlated with SOST serum levels. Multivariate analysis led to a significant association of SOST serum levels with age, DKK-1 and us-CRP.

Conclusion:

This study conducted in a large cohort of patients presenting with early axial SpA clearly showed an increase in DKK-1 serum levels, such increase being even more important in the sub group of patients with axial structural lesions. SOST was mainly correlated with age and to a lesser extend with DKK-1 serum levels and us-CRP. Their respective role in SpA pathogenesis needs further investigation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dkk1-serum-level-is-increased-in-recent-spondyloarthritis-and-is-associated-with-higher-prevalence-of-syndesmophytes-sclerostin-is-highly-correlated-with-age-data-from-the-desir-cohort/