Session Type: Abstract Submissions (ACR)
Background/Purpose: Both rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterised by bone erosion but aberrant bone formation is also a feature in PsA. Wnt proteins have recently been identified as key promoters of osteoblastogenesis hence new bone formation in inflammatory arthritis. Dickkopf-1 (Dkk-1) and sclerostin are natural inhibitors of Wnt signalling. Dkk-1 induces sclerostin expression by osteocytes and promotes osteoclastogenesis through suppression of osteoprotegerin (OPG). It has been shown that TNF-alpha inhibits bone formation by inducing Dkk-1 and sclerostin expression. The effect of anti-TNF on endogenous antagonists of the Wnt pathway in RA and PsA has not been studied previously in a prospective study design.
The aim of this study was to: (1) investigate serum levels of Dkk-1 and sclerostin in patients with RA and PsA; (2) compare both the very early (1 month) and more long-term (12 months) effects of anti-TNF treatment on inhibitors of Wnt signalling; and (3) explore associations between serum levels of Dkk-1 and sclerostin and acute phase response measures.
Methods: RA and PsA patients with active disease were recruited prior to starting anti-TNF therapy. Serum levels of Dkk-1, sclerostin and OPG were measured by ELISA at baseline, 1 month and 12 months and were related to CRP levels at all time points. OPG/Dkk-1 and OPG/sclerostin ratios were calculated from previously measured OPG levels.
Results: 62 patients (35 RA, 27 PsA) were recruited with a median age of 53 years (28-74) and median disease duration of 7 years. Older age was associated with lower sclerostin levels in the entire group (r=-0.316 p= 0.023).
No significant difference in Dkk-1 and sclerostin levels was observed between RA and PsA at any time point, though Dkk-1 levels were lower in PsA at 12 months approaching significance (p=0.08). Serum Dkk-1 and sclerostin levels did not change significantly with anti-TNF therapy in either RA or PsA during the course of the study. There were significant positive correlations between both DKK-1 and sclerostin levels across the different time points with the exception of DKK-1 between baseline and 1 year in both diseases. High serum sclerostin levels were associated with low Dkk-1 levels in PsA (r=-0.605 p= 0.04) and in the entire group (r=-0.453 p= 0.001) after 12 months of anti-TNF therapy.
OPG/Dkk-1 and OPG/sclerostin ratios reflecting remodeling balance were similar and did not change significantly in either RA or PsA during the study. There was no correlation between Dkk-1 or sclerostin and CRP levels.
Conclusion: This study provides data suggesting differences in the cross-talk between TNF-alpha, Dkk-1 and sclerostin between RA and PsA. After 12 months of anti-TNF treatment Dkk-1 levels were lower in PsA compared to RA. This may contribute to an imbalance in bone remodeling in favour of bone formation in PsA. High serum sclerostin levels were associated with low Dkk-1 levels in PsA and in the entire group after 12 months only suggesting that DKK-1 but not sclerostin might be altered with anti-TNF therapy. Neither Dkk-1 nor sclerostin correlated with CRP at any time point indicating that these Wnt inhibitors may not linked to inflammation.
H. P. Bhattoa,
O. M. FitzGerald,
Abbott Immunology Pharmaceuticals, Bristol-Myers Squibb,
Abbott Immunology Pharmaceuticals, UCB,
Abbott Immunology Pharmaceuticals,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/wnt-pathway-inhibitors-in-patients-with-psoriatic-and-rheumatoid-arthritis-treated-with-anti-tnf-therapy/