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.
Circulating Mediators of Bone Remodelling in Patients with Psoriatic and Rheumatoid Arthritis Treated with Anti-TNF-Alpha Therapy.
Szentpetery1, Agnes, Bhattoa2, Harjit P., Antal-Szalmas2, Peter, Szekanecz3, Zoltan, FitzGerald1, Oliver M.
St. Vincent's University Hospital, Dublin, Ireland
University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
University of Debrecen Medical and Health Sciences Center, Debrecen, Hungary
Dickkopf-1 (Dkk-1), an inhibitor of Wnt signalling, receptor activator of nuclear factor kappa B ligand (RANKL), an osteoclast differentiation factor and its soluble inhibitor osteoprotegerin (OPG) are key regulators of bone remodelling activity. Both rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterised by bone erosion; but bone formation is also a feature in PsA. The molecular basis of the different patterns of bone remodelling is unknown. It has been shown that TNF-alpha inhibits bone formation by up-regulating Dkk-1 and promotes osteoclastogenesis by stimulating RANKL production. The effect of anti-TNF-alpha on soluble mediators of bone remodelling in RA and PsA has not previously been compared in a prospective study design.
The aim of this study was to: (1) compare both the very early (1 month) and more long-term (12 months) effects of anti-TNF-alpha treatment on serum Dkk-1, RANKL and OPG in patients with RA and PsA; and (2) to explore associations between circulating mediators of bone remodelling and measurements of clinical parameters.
RA and PsA patients with active disease were recruited following a decision to start anti-TNF-alpha therapy. Serum was analysed for Dkk-1, RANKL and OPG by ELISA at baseline, 1 month and 12 months. Clinical assessments including ESR, CRP, and DAS28-CRP were recorded at all time points.
62 patients (35 RA, 27 PsA) were recruited. Mean disease duration was 9 years. Serum Dkk-1 and RANKL levels did not change in either RA or PsA during the course of the study. OPG levels were significantly higher at 1 year compared to 1 month in RA (p=0.03) whilst there was no significant difference in OPG observed in PsA during the study. Dkk-1 and RANKL levels were not significantly different comparing RA with PsA at any time point while Dkk-1 levels were lower at 1 year approaching significance (p=0.08). RANKL levels were lower at all time points in PsA. OPG levels were lower in PsA compared to RA at all time points with a significant reduction at 1 year (p=0.01). OPG/RANKL ratio reflecting remodelling balance was similar and did not change significantly in either RA or PsA during the course of the study.
OPG levels were correlated with ESR (r=0.42, p=0.04) and CRP levels (r=0.46, p=0.02) at baseline in PsA, whilst OPG levels were associated with ESR (r=0.43, p=0.04) and CRP (r=0.46, p=0.03) at 1 year in RA. No correlations were found between Dkk-1 and RANKL and markers of disease activity.
This study indicates differences in the regulation of bone remodelling between RA and PsA. Dkk-1 and RANKL levels may be lower in PsA consistent with both the fewer erosions and the accelerated bone formation seen in this disease. OPG, but not Dkk-1 and RANKL, is associated with markers of systemic inflammation in RA and PsA but increases further with effective treatment in RA suggesting that there is uncoupling between factors that drive inflammation and those responsible for erosive change.
To cite this abstract, please use the following information:
Szentpetery, Agnes, Bhattoa, Harjit P., Antal-Szalmas, Peter, Szekanecz, Zoltan, FitzGerald, Oliver M.; Circulating Mediators of Bone Remodelling in Patients with Psoriatic and Rheumatoid Arthritis Treated with Anti-TNF-Alpha Therapy. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :520