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AB0390 Serum RANKL Activity is Suppressed by TNF Alpha Inhibition but not with MTX Alone
  1. J. Nedovic1,
  2. B. Stamenkovic1,2,
  3. S. Stojanovic2
  1. 1Rheumatology
  2. 2Institute for rheumatology, Nis, Serbia

Abstract

Background Bone is, together with cartilage a central target of rheumatoid arthritis (RA). Chronic synovitis attacks the juxtaarticular bone, where it causes bone erosions. Formation of bone erosions is a consequence of osteoclasts activity. Osteoclasts are generated from mononuclear precursor cells mediated by the receptor activator of NF-kappaB ligand (RANKL). Tumor necrosis factor alpha (TNF) is considered as a most important proinflammatory cytokine and also, a mediator of structural damage in RA. TNF is an important inducer of osteoclast formation by increasing production of RANKL and is thus a key molecular link between inflammation and bone damage.

Objectives The aim of our study was to investigate whether the serum concentration of RANKL is influenced by therapy with and without TNF inhibitors or by disease activity itself.

Methods 45 RA patients (86,7% female, mean age 55,09±11,61 years) who fulfilled 1987. ACR criteria for RA and 20 age-matched controls with osteoarthritis were enrolled in the study. Group of RA patients consisted from 25 patients treated with Methotrexate (MTX group), mean disease duration 6,83±4,78 years and from 20 patients treated with Methotrexte and Etanercept (TNF group), mean disease duration 9,8±5,59 years. The serum levels of RANKL was determined by commercially available ELISA kit, values expressed in pg/ml. Disease activity was measured by Erythrocyte Sedimentation Rate (ESR) in mm, concentration of hsCRP in mg/L and wit composite index DAS28.

Results The mean values of serum concentrations of RANKL in MTX group, TNF group and in control group were: 246,81±226,06; 134,53±86,85 and 122,85±138,89 respectively. Patients in MTX group had statistically significantly higher values of RANKL compared with patients in TNF group and in control group, p<0,05. There were no significant differences between patients from TNF and control group. DAS28 was significantly higher in MTX group (6,08±1,16) compared to TNF group (3,18±1,04), p<0,001. Values of ESR were also higher in MTX group as compared to TNF group and control group: 41,44±18,68; 22,45±11,88 and 13,15±6,89 respectively, p<0,01 as well as the values of hsCRP: 9,91±14,45; 1,99±1,79 and 1,52±1,33, p<0,001. There were no significant differences between TNF and control group neither in level of ESR nor in hsCRP.

Conclusions In our study we determined that concomitant treatment with TNF blocker and MTX significantly reduce the concentration and thus activity of RANKL as compared to treatment with MTX alone. Thus, it is possible that the bone protective effect of anti TNF agents is at least partly, mediated through the RANKL. We also find that concentration of RANKL was in correlation with disease activity as expected.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.6016

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