Article Text

PDF

FRI0010 Effect of osteoprotegerin and pamidronate treatment in transgenic mice overexpressing human tnf-alpha
  1. K Redlich1,
  2. A Maier2,
  3. S Hayer1,
  4. G Kollias3,
  5. CR Dunstan4,
  6. S Lang5,
  7. W Woloszczuk6,
  8. G Steiner1,
  9. J Smolen1,
  10. G Schett1
  1. 1Internal Medicine III, Division of Rheumatology
  2. 2Department of Radiology
  3. 3Department. of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece
  4. 4Department of Pathology, Amgen, Inc., California, USA
  5. 5Department of Pathology
  6. 6Ludwig Boltzmann-Institute of Exp. Endocrinology, University of Vienna, Vienna, Austria

Abstract

Background Rheumatoid arthritis (RA) is characterised by progressive joint destruction resulting from chronic inflammation. Recent studies suggest that bone-resorbing osteoclasts formed in the synovium play an important role in bone destruction in RA.

Objectives We studied the effect of anti-resorptive treatment with osteoprotegerin and/or pamidronate compared to TNF blockade with infliximab on the development of erosions in TNF overexpressing mice.

Methods Systemic treatment with osteoprotegerin (OPG), pamidronate, both osteoprotegerin and pamidronate, infliximab or phosphate buffered saline (PBS) was carried out by intravenous injection. Treatment was initiated at the time of onset of arthritis and continued over 35d. Clinical, serological, radiological and histological outcomes were assessed after treatment.

Results Clinical improvement, as assessed by reduction in paw swelling was only seen in the infliximab treated group. X-Rays of the hind paws were performed to quantify erosive changes. Erosions were detectable in each joint compartment Grading of erosions was performed analogous to the Larsen score. There was a marked and significant (p < 0.05) reduction in the Larsen scores of mice treated with OPG (-54%), OPG and pamidronate (-64%) and infliximab (-66%). Microscopic examination of decalcified joint tissue sections using a semiquantitative method, revealed a significant (p < 0.05) reduction in the extent of erosions in all treatment groups (OPG: -56%; pamidronate: -53%; OPG + pamidronate: -81%; infliximab ?46%) when compared to controls.

Conclusion These data suggest that anti-resorptive treatment may have a significant potential in TNF-mediated bone destruction.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.