TY - JOUR

T1 - Novel porcine model of implant-associated osteomyelitis

T2 - A comprehensive analysis of local, regional, and systemic response

AU - Jensen, Louise Kruse

AU - Koch, Janne

AU - Dich-Jørgensen, Kristine

AU - Aalbaek, Bent

AU - Petersen, Andreas

AU - Fuursted, Kurt

AU - Bjarnsholt, Thomas

AU - Kragh, Kasper Nørskov

AU - Tøtterup, Mikkel

AU - Bue, Mats

AU - Hanberg, Pelle

AU - Søballe, Kjeld

AU - Heegaard, Peter M H

AU - Jensen, Henrik Elvang

N1 - © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

PY - 2017

Y1 - 2017

N2 - 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 (>10(8) CFU) 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 10(4) CFU (n = 26) or 10(2) and 10(3) CFU (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.IN CONCLUSION: 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.

AB - 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 (>10(8) CFU) 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 10(4) CFU (n = 26) or 10(2) and 10(3) CFU (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.IN CONCLUSION: 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.

U2 - 10.1002/jor.23505

DO - 10.1002/jor.23505

M3 - Journal article

C2 - 27958656

VL - 35

SP - 2211

EP - 2221

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 10

ER -