Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pathogenesis of osteomyelitis

Madhuri M Sopirala, MD, MPH
Section Editor
Daniel J Sexton, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Osteomyelitis is a progressive infection of bone that results in inflammatory destruction followed by new bone formation. Three major categories are based upon pathogenic mechanisms of infection [1]:

Osteomyelitis secondary to a contiguous focus of infection (eg, after trauma, surgery, or insertion of a prosthetic joint).

Osteomyelitis secondary to a contiguous focus of infection associated with vascular insufficiency, primarily occurring in patients with diabetes mellitus and/or peripheral vascular disease.

Osteomyelitis following hematogenous spread of infection, which is the major mechanism in vertebral osteomyelitis and in children. It was previously thought that spread of infection may occur via vertebral veins known as Batson's plexus, especially from sites of infection in bowel or urinary tract. Seeding beneath the vertebral endplate is followed by involvement of the disc and other adjoining vertebrae. Blood vessels in pediatric spine terminate within the intervertebral disc, allowing for direct extension of infection [2]. Many experts now believe that the corkscrewing of the vertebral arterial supply leads to vertebral osteomyelitis in patients with bacteremia.

Acute osteomyelitis evolves over several days to weeks and can progress to a chronic infection [1]. The hallmark of chronic osteomyelitis is the presence of dead bone (sequestrum). Other common features of chronic osteomyelitis include involucrum (reactive bony encasement of the sequestrum), local bone loss, and, if there is extension through cortical bone, sinus tracts.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: May 02, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Lew DP, Waldvogel FA. Osteomyelitis. Lancet 2004; 364:369.
  2. Batson OV. The vertebral system of veins as a means for cancer dissemination. Prog Clin Cancer 1967; 3:1.
  3. Foster TJ, Höök M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 1998; 6:484.
  4. Herrmann M, Vaudaux PE, Pittet D, et al. Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis 1988; 158:693.
  5. Johansson A, Flock JI, Svensson O. Collagen and fibronectin binding in experimental staphylococcal osteomyelitis. Clin Orthop Relat Res 2001; :241.
  6. Yacoub A, Lindahl P, Rubin K, et al. Purification of a bone sialoprotein-binding protein from Staphylococcus aureus. Eur J Biochem 1994; 222:919.
  7. Rydén C, Tung HS, Nikolaev V, et al. Staphylococcus aureus causing osteomyelitis binds to a nonapeptide sequence in bone sialoprotein. Biochem J 1997; 327 ( Pt 3):825.
  8. Shirtliff ME, Leid JG, Costerton JW. The Basic Science of Musculoskeletal Infections. In: Musculoskeletal Infections, Calhoun JH, Mader JT (Eds), Marcel Decker, New York 2003.
  9. Patti JM, Bremell T, Krajewska-Pietrasik D, et al. The Staphylococcus aureus collagen adhesin is a virulence determinant in experimental septic arthritis. Infect Immun 1994; 62:152.
  10. Switalski LM, Patti JM, Butcher W, et al. A collagen receptor on Staphylococcus aureus strains isolated from patients with septic arthritis mediates adhesion to cartilage. Mol Microbiol 1993; 7:99.
  11. Patti JM. A humanized monoclonal antibody targeting Staphylococcus aureus. Vaccine 2004; 22 Suppl 1:S39.
  12. Xu Y, Rivas JM, Brown EL, et al. Virulence potential of the staphylococcal adhesin CNA in experimental arthritis is determined by its affinity for collagen. J Infect Dis 2004; 189:2323.
  13. Therrien R, Lacasse P, Grondin G, Talbot BG. Lack of protection of mice against Staphylococcus aureus despite a significant immune response to immunization with a DNA vaccine encoding collagen-binding protein. Vaccine 2007; 25:5053.
  14. Patti JM, Boles JO, Höök M. Identification and biochemical characterization of the ligand binding domain of the collagen adhesin from Staphylococcus aureus. Biochemistry 1993; 32:11428.
  15. Buck AW, Fowler VG Jr, Yongsunthon R, et al. Bonds between fibronectin and fibronectin-binding proteins on Staphylococcus aureus and Lactococcus lactis. Langmuir 2010; 26:10764.
  16. Williams RJ 3rd, Smith RL, Schurman DJ. Septic arthritis. Staphylococcal induction of chondrocyte proteolytic activity. Arthritis Rheum 1990; 33:533.
  17. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med 1997; 336:999.
  18. Norden CW. Lessons learned from animal models of osteomyelitis. Rev Infect Dis 1988; 10:103.
  19. Webb LX, Wagner W, Carroll D, et al. Osteomyelitis and intraosteoblastic Staphylococcus aureus. J Surg Orthop Adv 2007; 16:73.
  20. Ellington JK, Harris M, Hudson MC, et al. Intracellular Staphylococcus aureus and antibiotic resistance: implications for treatment of staphylococcal osteomyelitis. J Orthop Res 2006; 24:87.
  21. Greenberg DP, Bayer AS, Cheung AL, Ward JI. Protective efficacy of protein A-specific antibody against bacteremic infection due to Staphylococcus aureus in an infant rat model. Infect Immun 1989; 57:1113.
  22. Gemmell CG, Goutcher SC, Reid R, Sturrock RD. Role of certain virulence factors in a murine model of Staphylococcus aureus arthritis. J Med Microbiol 1997; 46:208.
  23. Nair S, Song Y, Meghji S, et al. Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity. J Bone Miner Res 1995; 10:726.
  24. Littlewood-Evans AJ, Hattenberger MR, Lüscher C, et al. Local expression of tumor necrosis factor alpha in an experimental model of acute osteomyelitis in rats. Infect Immun 1997; 65:3438.
  25. Schlievert PM. Role of superantigens in human disease. J Infect Dis 1993; 167:997.
  26. Loughran AJ, Gaddy D, Beenken KE, et al. Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus. Infect Immun 2016; 84:2586.
  27. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med 1970; 282:198.
  28. Mader JT, Calhoun JH. Osteomyelitis. In: Principles and Practice of Infectious Diseases, Mandell GL, Douglas RG, Bennett Jr JE (Eds), Churchill Livingstone, New York 1995. p.1039.
  29. De Boeck H. Osteomyelitis and septic arthritis in children. Acta Orthop Belg 2005; 71:505.
  30. Morrissey RT. Bone and Joint Infections. In: Lovell and Winter's Pediatric Ortopaedics, 3rd ed, Morrissey RT (Ed), Lippincott, Philadelphia 1990. p.539.
  31. Hobo T. Zur Pathogenesed er akuten haematogenen Osteomyelitism, it Beriicksichtigundger Vitalfarbungslehre. Acta Scholae Medicina Universitas Imperialis Kioto 1921; 4:1.
  32. Howlett CR. The fine structure of the proximal growth plate and metaphysis of the avian tibia: endochondral osteogenesis. J Anat 1980; 130:745.
  33. Ham KN, Hurley JV, Ryan GB, Storey E. Localization of particulate carbon in metaphyseal vessels of growing rats. Aust J Exp Biol Med Sci 1965; 43:625.
  34. Emslie KR, Nade S. Pathogenesis and treatment of acute hematogenous osteomyelitis: evaluation of current views with reference to an animal model. Rev Infect Dis 1986; 8:841.
  35. Jansson A, Jansson V, von Liebe A. [Pediatric osteomyelitis]. Orthopade 2009; 38:283.
  36. Calhoun JH, Manring MM. Adult osteomyelitis. Infect Dis Clin North Am 2005; 19:765.