- Poster presentation
Distinct patterns of RANKL/osteoprotegerin system modulation through anti-tumour necrosis factor and corticosteroid therapy in rheumatoid arthritis synovium
Arthritis Research & Therapy volume 7, Article number: P81 (2005)
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).
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.
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.
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.
About this article
Cite this article
Catrina, A., Makrygiannakis, D., af Klint, E. et al. Distinct patterns of RANKL/osteoprotegerin system modulation through anti-tumour necrosis factor and corticosteroid therapy in rheumatoid arthritis synovium. Arthritis Res Ther 7, P81 (2005). https://doi.org/10.1186/ar1602
- Rheumatoid Arthritis
- Rheumatoid Arthritis Synovium
- RANKL Expression