Archives of Orthopaedic and Trauma Surgery

, Volume 125, Issue 3, pp 169–176 | Cite as

Establishment of rat model of acute staphylococcal osteomyelitis: relationship between inoculation dose and development of osteomyelitis

  • Nobuaki Fukushima
  • Kazuhiko YokoyamaEmail author
  • Takeshi Sasahara
  • Yoh Dobashi
  • Moritoshi Itoman
Original Article



Many animal models of acute and chronic osteomyelitis have been developed. In these models, osteomyelitic lesions are induced using sclerosing agents and foreign bodies with bacterial strains. In the present rat model, these sclerosing agents were not used. We assessed the relationship between inoculation dose and histological, radiological, and microbiological changes in the acute phase (1 week after inoculation) using this rat osteomyelitis model.

Materials and methods

An experimental rat model of acute osteomyelitis was developed by direct inoculation of the virulent strain BB of Staphylococcus aureus into tibial bone without sclerosants. To examine the relationship between the inoculation dose of the bacteria and the progression of the osteomyelitis, the inoculated lesions were assessed for changes in histological, radiological, and bacteriological parameters at 1 week after infection. Serial dilutions of the bacteria [6×101 to 6×105 colony-forming units (CFU)/5 μl] suspended in saline or saline alone were inoculated into the proximal metaphysis of the tibia.


Development of significant histological and radiological signs of osteomyelitis required an inoculum of at least 6×103 CFU/5 μl. The number of viable bacteria at the lesion reached a maximum of 6×103 CFU/5 μl.


These results suggest that strain BB induces the development of acute staphylococcal osteomyelitis with clear infective destruction in the tibia, and that our model may be applied to the identification of virulence factors in studies of posttraumatic osteomyelitis.


Acute osteomyelitis Experimental model Rat Inoculation dose Infectious progression 


  1. 1.
    Andriole VT, Nagel DA, Southwick WO (1973) A paradigm for human chronic osteomyelitis. J Bone Joint Surg Am 55:1511–1515Google Scholar
  2. 2.
    Cash HA, Woods DE, McCullough B, Johanson WG, Bass JA (1979) A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am Rev Respir Dis 119:453–459Google Scholar
  3. 3.
    Cremieux AC, Carbon C (1977) Experimental models of bone and prosthesis joint infections. Clin Infect Dis 25:1295–1302Google Scholar
  4. 4.
    Deysine, Rosario E, Isenberg HD (1976) Acute osteomyelitis: an experimental model. Surgery 79:97–99Google Scholar
  5. 5.
    Fitzgerald RH (1983) Experimental osteomyelitis: description of a canine model and the role of depot administration of antibiotics in the prevention and treatment of sepsis. J Bone Joint Surg Am 65:371–380Google Scholar
  6. 6.
    Hasegawa N, San Clemente CL (1978) Virulence and immunity of Staphylococcus aureus BB and certain deficient mutants. Infect Immun 22:473–479Google Scholar
  7. 7.
    Hasegawa N, Kondo I, Hoshina S, Kurosaki K, Igarashi H (1983) Effect of highly purified coagulase and culture filtrate on virulence and immunity of a coagulase-negative mutant of Staphylococcus aureus BB. Infect Immun 39:1236–1242Google Scholar
  8. 8.
    LaMont JT, Sonnenblick EB, Rothman S (1979) Role of clostridial toxin in the pathogenesis of clindamycin colitis in rabbits. Gastroenterology 70:356–361Google Scholar
  9. 9.
    Mader JT (1985) Animal models of osteomyelitis. Am J Med 78 (Suppl 6B): 213–217CrossRefGoogle Scholar
  10. 10.
    Nelson DR, Buxton TB, Luu QNL, Rissing JP (1990) An antibiotic resistant experimental model of Pseudomonas osteomyelitis. Infection 18:246–249Google Scholar
  11. 11.
    Nelson DR, Buxton TB, Luu QN, Rissing JP (1990) The promotional effect of bone wax on experimental Staphylococcus aureus osteomyelitis. J Thorac Cardiovasc Surg 99:977–980Google Scholar
  12. 12.
    Norden CW (1970) Experimental osteomyelitis. I. A description of the model. J Infect Dis 122:410–418Google Scholar
  13. 13.
    Norden CW (1988) Lessons learned from animal models of osteomyelitis. Rev Infect Dis 10:103–110Google Scholar
  14. 14.
    Passl R, Müller CH, Zielinski CC, Eibl MM (1984) A model of experimental post-traumatic osteomyelitis in guinea pigs. J Trauma 24:323–326Google Scholar
  15. 15.
    Power ME, Olson ME, Domingue PAG, Costerton JW (1990) A rat model of Staphylococcus chronic osteomyelitis that provides a suitable system for studying the human infection. J Med Microbial 33:189–198Google Scholar
  16. 16.
    Rissing JP, Buxton TB, Weinstein RS, Shockley RK (1985) Model of experimental chronic osteomyelitis in rats. Infect Immun 47:581–586Google Scholar
  17. 17.
    Rissing JP, Buxton TB, Fisher J, Harris R, Shockley RK (1985) Arachidonic acid facilitates experimental chronic osteomyelitis in rats. Infect Immun 49:141–144Google Scholar
  18. 18.
    Rissing JP (1990) Animal models of osteomyelitis: knowledge, hypothesis, and speculation. Infect Dis Clin North Am 4:377–390Google Scholar
  19. 19.
    Rodet A (1885) Physiologie pathologique-ètude expèrimentale sur l’ostèomyelite infectieuse. CR Acad Sci 99:569–571Google Scholar
  20. 20.
    Scherman L, Janota M, Lewin P (1941) The production of experimental osteomyelitis: preliminary report. JAMA 117:1525–1529Google Scholar
  21. 21.
    Spagnolo N, Greco F, Rossi A, Ciolli L, Teti A, Posteraro P (1993) Chronic staphylococcal osteomyelitis: a new experimental rat model. Infect Immun 61:5225–5230Google Scholar
  22. 22.
    Smeltzer MS, Thomas JR, Hickmon SG, Skinner RA, Nelson CL, Griffith D, Parr Jr TR, Evans RP (1997) Characterization of rabbit model of staphylococcal osteomyelitis. J Orthop Res 15:414–421Google Scholar
  23. 23.
    Wilensky AO (1927) The mechanism and pathogenesis of acute osteomyelitis. Am J Surg 3:281–289CrossRefGoogle Scholar
  24. 24.
    Zak O, Zak F, Rich R, Tosch W, Kradolfer F, Scheld WM (1982) Experimental staphylococcal osteomyelitis in rats: therapy with rifampin and cloxacillin alone or in combination. In: Perty P, Grassi GG (eds) Current chemotherapy and immunotherapy. American Society for Microbiology, Washington DC, pp 973–974Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Nobuaki Fukushima
    • 1
  • Kazuhiko Yokoyama
    • 1
    Email author
  • Takeshi Sasahara
    • 2
  • Yoh Dobashi
    • 3
  • Moritoshi Itoman
    • 1
  1. 1.Department of Orthopedic Surgery, School of MedicineKitasato UniversityKanagawa Japan
  2. 2.Department of Microbiology, School of MedicineKitasato UniversityKanagawa Japan
  3. 3.Department of Pathology, Faculty of MedicineUniversity of YamanashiYamanashiJapan

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