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Ann Rheum Dis doi:10.1136/ard.2008.104786

IL-1 is essential for systemic inflammatory bone loss

  1. Karin Polzer
  1. University of Erlangen-Nuremberg, Germany
    1. Leo Joosten
    1. Radboud University Medical Center Nijmegen, Netherlands
      1. Jürg Gasser
      1. Novartis Biomedical Research Institutes, Switzerland
        1. Jörg H Distler
        1. University of Erlangen-Nuremberg, Germany
          1. Gisela Ruiz
          1. University of Erlangen-Nuremberg, Germany
            1. Wolfgang Baum
            1. University of Erlangen-Nuremberg, Germany
              1. Kurt Redlich
              1. Medical University of Vienna, Austria
                1. Klaus Bobacz
                1. Medical University of Vienna, Austria
                  1. Josef S Smolen
                  1. Medical University of Vienna, Austria
                    1. Wim van den Berg
                    1. Radboud University Medical Center Nijmegen, Netherlands
                      1. Georg Schett
                      1. University of Erlangen-Nuremberg, Germany
                        1. Jochen Zwerina (jochen.zwerina{at}uk-erlangen.de)
                        1. University of Erlangen-Nuremberg, Germany
                          • Published Online First 5 February 2009

                          Abstract

                          Objectives: Chronic inflammation is a major risk factor of systemic bone loss leading to osteoporotic fracture and substantial morbidity and mortality. Inflammatory cytokines, particularly TNF and IL-1 are thought to play a key role in the pathogenesis of inflammation-induced bone loss, but their exact roles are yet to be determined.

                          Methods: To determine whether TNF directly triggers bone loss or requires interleukin-1 (IL-1), we crossed human tumor necrosis factor alpha (hTNFtg) mice with mice lacking IL-1α and IL-1β (IL-1-/-hTNFtg). Systemic bone architecture was evaluated using computed tomography analysis, static and dynamic bone histomorphometry as well as serum markers of bone metabolism.

                          Results: hTNFtg mice developed severe bone loss accompanied by a severe distortion of bone microarchitecture. Bone trabeculae were both thinner and decreased in numbers resulting in an increased trabecular separation. Histomorphometric analyses revealed strongly increased bone resorption in hTNFtg mice as compared to wildtype mice. In contrast, IL-1-/-hTNFtg mice were fully protected from systemic bone loss despite still developing inflammation in their joints. Lack of IL-1 completely reverted increased osteoclast formation and bone resorption in hTNFtg mice as well as the increased levels of RANKL in these mice. Both structural parameters as well as osteoclast and osteoblast numbers were indistinguishable from wildtype mice.

                          Conclusion: These data indicate that IL-1 is essential for TNF-mediated bone loss. Despite TNF-mediated inflammatory arthritis, systemic bone is fully protected by the absence of IL-1, which suggests that IL-1 is an essential mediator of inflammatory osteopenia.

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