Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

Distinct patterns of RANKL/osteoprotegerin system modulation through anti-tumour necrosis factor and corticosteroid therapy in rheumatoid arthritis synovium

  • AI Catrina1,
  • D Makrygiannakis1,
  • E af Klint1,
  • SB Catrina2,
  • S Ernestam3,
  • L Klareskog1 and
  • AK Ulfgren1
Arthritis Research & Therapy20057(Suppl 1):P81

DOI: 10.1186/ar1602

Received: 11 January 2005

Published: 17 February 2005

Background

Anti-tumour necrosis factor (TNF) therapy with both etanercept and infliximab decreases radiographic progression of patients with rheumatoid arthritis (RA), while the effect of local corticosteroid injections, a routine adjuvant therapy in arthritis, on bone metabolism is still debated. Thus, we investigated the effect of both anti-TNF and local corticosteroid therapy on synovial expression of osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL).

Methods

OPG and RANKL were evaluated by immunohistochemistry in serial synovial biopsies obtained from 18 RA patients before and after 8 weeks of treatment with etanercept (nine patients) or infliximab (nine patients). Eighteen additional patients with arthritis that received a local corticosteroid injection were evaluated before and after 2 weeks of the injection. Biopsies were evaluated by double-blind semi-quantitative analysis and image analysis. The in vitro effect of TNF antagonists and corticosteroids (dexametasone) on RANKL/OPG expression in osteoblasts was evaluated by western blot. Statistical analysis was performed using the Wilcoxon's signed-rank test followed by Bonferroni correction.

Results

OPG was present in all biopsies with a characteristic pattern restricted mainly to the endothelial cells and few mononuclear cells. RANKL was present mainly in the T-cell area and to a lesser extent on some endothelial cells, but absent in other mononuclear cells. Treatment with both infliximab and etanercept increased synovial OPG expression. Neither infliximab nor etanercept influenced RANKL expression following 8 weeks of treatment. The RANKL/OPG ratio decreased following therapy in both groups, the effect being more pronounced in the responders as compared with non-responders to therapy. Local corticosteroid treatment resulted in a similar change of the RANKL/OPG ratio through a different mechanism, with a significant decrease of the synovial RANKL and no changes in the OPG expression. In vitro both TNF antagonists and corticosteroids mimicked the in vivo effect inducing a decrease in the RANKL/OPG ratio in TNF-primed osteoblasts.

Conclusion

Therapy with both TNF antagonists and local corticosteroids modulates the RANKL/OPG system, inhibiting bone destruction through distinct mechanisms. Thus, association of these two therapies may be beneficial in preventing bone erosions in RA.

Authors’ Affiliations

(1)
Department of Rheumatology, Karolinska University Hospital, Solna, Karolinska Institutet
(2)
Department of Molecular Medicine, Karolinska University Hospital, Solna, Karolinska Institutet
(3)
Department of Rheumatology, Karolinska University Hospital, Huddinge, Karolinska Institutet

Copyright

© BioMed Central Ltd 2005

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