Abstract
BackgroundThe 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.MethodsA 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.ResultsHigh 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.ConclusionsHigh 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.
Highlights
The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is an important regulator during fracture healing
Clinical assessment As described previously, the human tumor necrosis factor transgenic (hTNFtg) mice are smaller in size and weight compared to their wild type littermates or were dislocated or fragmentary, and were excluded from further analyses
After 28 days of healing there was no significant difference in the maximum torque between the wild type group and both hTNFtg groups, the standard deviation was high in the hTNFtg group without treatment (Figure 3)
Summary
The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is an important regulator during fracture healing. 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. Inflammatory diseases such as rheumatoid arthritis (RA), do increase the risk of fractures [1,2] but may impair fracture healing by delaying the process and leading to non-unions [3]. TNF-blocking agents combine a strong anti-inflammatory potential leading to direct protection of bone and cartilage [8]
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