Volume 6 Supplement 3

Global Arthritis Research Network (GARN): 4th World Congress on Arthritis in Montreal

Open Access

Zoledronic acid protects from local and systemic bone loss in tumor necrosis factor-mediated arthritis

  • K Redlich1,
  • P Herrak1,
  • B Görtz1,
  • S Hayer1,
  • E Reiter1,
  • J Gasser2,
  • H Bergmeister3,
  • G Kollias4,
  • JS Smolen1 and
  • G Schett1
Arthritis Res Ther20046(Suppl 3):88

https://doi.org/10.1186/ar1423

Published: 13 September 2004

Increased osteoclast activity is a key factor for bone loss in rheumatoid arthritis (RA). This suggests that osteoclast-targeted therapies could effectively prevent skeletal damage in RA. Zoledronic acid (ZA) is one of the most potent agents to block osteoclast function. We therefore investigated whether ZA can inhibit inflammatory bone loss.

Human tumor necrosis factor transgenic (hTNFtg) mice, which develop severe destructive arthritis as well as osteoporosis, were treated with PBS, single or repeated doses of ZA, calcitonin or anti-tumor necrosis factor at the onset of arthritis.

Synovial inflammation was not affected by ZA. In contrast, bone erosion was retarded by single administration (-60%) and almost completely blocked by repeated administration (-95%) of ZA. Cartilage damage was partly inhibited (-40%), and synovial osteoclast counts were significantly reduced upon ZA treatment. Systemic bone mass dramatically increased in hTNFtg mice upon ZA administration, which was due to an increase of trabecular number and connectivity. In addition, bone resorption parameters were significantly lowered after ZA. Calcitonin had no effect on synovial inflammation, bone erosions, cartilage damage or systemic bone mass. Anti-tumor necrosis factor entirely blocked synovial inflammation, bone erosion, synovial osteoclast formation and cartilage damage, but had only minor effects on systemic bone mass.

ZA appears as an effective tool to protect bone from arthritic damage. In addition to antiinflammatory drug therapy, modern bisphosphonates are promising candidates to maintain joint integrity and to reverse systemic bone loss in arthritis.

Authors’ Affiliations

(1)
Division of Rheumatology, Department of Internal Medicine III, University of Vienna
(2)
(3)
Institute of Biological Sciences, University of Vienna
(4)
Molecular Genetics Laboratory, Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center

Copyright

© The Author(s) 2004

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