title: Influence of antiTNF-alpha antibody treatment on fracture healing under chronic inflammation.
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.
authors.affiliation: Institute for Experimental Muskuloskeletal Medicine IEMM, University Hospital Muenster, Muenster, Germany. Melanie.Timmen@ukmuenster.de.
authors.forename: Melanie
authors.initials: M
authors.lastname: Timmen
authors.forename: Heriburg
authors.initials: H
authors.lastname: Hidding
authors.forename: Britta
authors.initials: B
authors.lastname: Wieskötter
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baum
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raschke
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Richard
authors.initials: R
authors.lastname: Stange
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001168:Arthritis / Q000150:complications* / Q000188:drug therapy; D001172:Arthritis, Rheumatoid; D001858:Bone Nails; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005593:Fracture Fixation, Internal; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007249:Inflammation; D000069285:Infliximab; D051379:Mice; D008822:Mice, Transgenic; D013314:Stress, Mechanical; D019415:Torque; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D016474:Weight-Bearing
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab