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

BMC Musculoskeletal Disorders

Richard Stange²  Jochen Zwerina⁴  Georg Schett¹  Michael J Raschke³  Thomas Pap²  Wolfgang Baum¹  Britta Wieskötter³  Heriburg Hidding²  Melanie Timmen² 

[1] Department of Internal Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany;Institute for Experimental Muskuloskeletal Medicine IEMM, University Hospital Muenster, Muenster, Germany;Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, Muenster, Germany;Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria

关键词: Treatment;    Rheumatoid arthritis;    Fracture healing;    Inflammation;    Anti-TNFα;   

Others  :  1125629
DOI  :  10.1186/1471-2474-15-184

 received in 2014-02-27, accepted in 2014-05-16,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Timmen et al.; licensee BioMed Central Ltd.

【 图 表 】

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