title: Novel porcine model of implant-associated osteomyelitis: A comprehensive analysis of local, regional, and systemic response.
abstract: Pigs are favorable experimental animals for infectious diseases in humans. However, implant-associated osteomyelitis (IAO) models in pigs have only been evaluated using high-inoculum infection (>108CFU) models in 1975 and 1993. Therefore, the aim of this paper was to present a new low inoculum porcine model of human IAO based on 42 experimental pigs. The model was created by drilling an implant cavity in the tibial bone followed by insertion of a small steel implant and simultaneous inoculation of Staphylococcus aureus bacteria (n = 32) or saline (n = 10). The infected pigs were either inoculated with 104CFU (n = 26) or 102and 103CFU (n = 6). All animals were euthanized 5 days after insertion of implants. Pigs receiving the high-inoculum infections showed a significantly higher volume of bone lesion, number of neutrophils around the implant, concentrations of acute phase proteins in serum, and enlargement of regional lymph nodes. A positive correlation was present between a high number of surrounding neutrophils and high values of all other parameters. Furthermore, a threshold of 40 neutrophils per 10 high power fields for the histopathological diagnosis of high grade IAO was defined.
  
  
  
  This paper describes a novel low-inoculum S. aureus porcine model of IAO which was demonstrated to be reliable, reproducible and discriminative to human IAO, and represents a requested and valuable tool in orthopedic research. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2211-2221, 2017.
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Louise Kruse
authors.initials: LK
authors.lastname: Jensen
authors.affiliation: Department of Experimental Medicine, University of Copenhagen, Blegdamsvej 2, 2200, Copenhagen N, Denmark.
authors.forename: Janne
authors.initials: J
authors.lastname: Koch
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Dich-Jorgensen
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Aalbaek
authors.affiliation: Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Petersen
authors.affiliation: Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark.
authors.forename: Kurt
authors.initials: K
authors.lastname: Fuursted
authors.affiliation: Costerton Biofilm Center, Institute of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.|Department of Clinical Microbiology, Copenhagen University Hospital, Juliane Maries Vej 22, 2100, Copenhagen Ø, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjarnsholt
authors.affiliation: Costerton Biofilm Center, Institute of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
authors.forename: Kasper Nørskov
authors.initials: KN
authors.lastname: Kragh
authors.affiliation: Orthopedic Research Unit, Aarhus University Hospital, Building 1A, Nørrebrogade 44, 8000, Aarhus, Denmark.|Department of Orthopedic Surgery, Randers Regional Hospital, Skovlyvej 15, 8930, Randers NØ, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Tøtterup
authors.affiliation: Orthopedic Research Unit, Aarhus University Hospital, Building 1A, Nørrebrogade 44, 8000, Aarhus, Denmark.|Department of Orthopedic Surgery, Horsens Regional Hospital, Sundvej 30, 8700, Horsens, Denmark.
authors.forename: Mats
authors.initials: M
authors.lastname: Bue
authors.affiliation: Orthopedic Research Unit, Aarhus University Hospital, Building 1A, Nørrebrogade 44, 8000, Aarhus, Denmark.
authors.forename: Pelle
authors.initials: P
authors.lastname: Hanberg
authors.affiliation: Orthopedic Research Unit, Aarhus University Hospital, Building 1A, Nørrebrogade 44, 8000, Aarhus, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
authors.affiliation: Innate Immunology Group, National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870, Frederiksberg C, Denmark.
authors.forename: Peter M H
authors.initials: PMH
authors.lastname: Heegaard
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark.
authors.forename: Henrik Elvang
authors.initials: HE
authors.lastname: Jensen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D010019:Osteomyelitis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D016459:Prosthesis-Related Infections / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D013552:Swine; D014057:Tomography, X-Ray Computed
keywords: S. aureus; animal model; osteomyelitis; peri-prosthetic infection