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Open Access Research article

Influence of antiTNF-alpha antibody treatment on fracture healing under chronic inflammation

Melanie Timmen2*, Heriburg Hidding2, Britta Wieskötter1, Wolfgang Baum3, Thomas Pap2, Michael J Raschke1, Georg Schett3, Jochen Zwerina4 and Richard Stange12

Author Affiliations

1 Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, Muenster, Germany

2 Institute for Experimental Muskuloskeletal Medicine IEMM, University Hospital Muenster, Muenster, Germany

3 Department of Internal Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

4 Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria

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BMC Musculoskeletal Disorders 2014, 15:184  doi:10.1186/1471-2474-15-184

Published: 29 May 2014

Abstract

Background

The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid arthritis (RA) and elucidate the question whether enduring the anti TNF-α therapy after trauma is beneficial or not.

Methods

A standardized femur fracture was applied to wild type and human TNF-α transgenic mice (hTNFtg mice), which develop an RA-like chronic polyarthritis. hTNFtg animals were treated with anti-TNF antibody (Infliximab) during the fracture repair. Untreated animals served as controls. Fracture healing was evaluated after 14 and 28 days of treatment by clinical assessment, biomechanical testing and histomorphometry.

Results

High levels of TNF-α influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-α in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type.

Conclusions

High levels of TNF-α during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-α inhibition by an anti-TNF antibody does not interfere with fracture healing.

Keywords:
Anti-TNFα; Inflammation; Fracture healing; Rheumatoid arthritis; Treatment