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

Background: The overexpression of tumor necrosis factor (TNF)-alpha 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-alpha inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-alpha driven animal model of human rheumatoid arthritis (RA) and elucidate the question whether enduring the anti TNF-alpha therapy after trauma is beneficial or not. Methods: A standardized femur fracture was applied to wild type and human TNF-alpha 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-alpha influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-alpha in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type. Conclusions: High levels of TNF-alpha during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-alpha inhibition by an anti-TNF antibody does not interfere with fracture healing.