D.V. RIMASHEVSKIY¹, I.F. AKHTYAMOV², P.N. FEDULICHEV³

 ¹People’s Friendship University of Russia, Moscow

²Kazan State Medical University, Kazan

³S.I. Georgievsky Medical Academy оf V.I. Vernadsky Crimean Federal University, Simferopol

Contact details:

Rimashevskiy D.V. — PhD (Medicine), Associate Professor of the Traumatology and Orthopedics Department

Address: 6 Miklukho-Maklaya St., Moscow, Russian Federation, 117198, tel.: +7-909-943-06-18, e-mail: drimashe@yandex.ru

Today, large-scale studies of various aspects of osteomyelitis and the search for new methods of treatment did not prevent us from failure to achieve infection eradication in a big part of osteomyelitis patients. Often, we are not able to fully restore the function of the affected part of the body. A special problem of recent decades is implant-associated osteomyelitis since the number of hardware implanted by trauma and orthopedic surgeons continues to rise every year, and the frequency of postoperative infectious complications does not decrease despite all efforts to prevent them. The social significance of osteomyelitis is difficult to overestimate. This is not only a large cost to the health system for the treatment of patients, but also a decrease in the quality and life expectancy of patients. Perhaps our failures in the treatment of osteomyelitis are due to our incomplete understanding of the etiology and pathogenesis of the disease and the inconsistency of interdisciplinary interaction.

This lecture summarizes the current understanding of the etiology and pathogenesis of osteomyelitis, the most popular classifications of the disease both in terms of age and etiology, the route of infection into the bone, the clinical course, the anatomical type of bone damage and the physiological class of patients.

Key words: osteomyelitis, etiology, pathogenesis, classification, diagnosis and treatment.

REFERENCES

1. Breasted J.H. New-York Historical Society Library. The Edwin Smith Surgical Papyrus. Chicago: The University of Chicago Press, 1930.
2. Klenerman L. A history of osteomyelitis from the Journal of Bone and Joint Surgery: 1948 to 2006. J. Bone Jt. Surg. Br, 2007, vol. 89, pp. 667–670. DOI: 10.1302/0301-620X.89B5.19170
3. Schwarz E.M. et al. The 2018 International Consensus Meeting on Musculoskeletal Infection: research priorities from the General Assembly Questions. J. Orthop. Res, 2019, vol. 37, pp. 997–1006. DOI: 10.1002/jor.24293
4. Rimashevskiy D.V., Kurmangaliev E.T, Belokobylov A.A., Batpenov N.D., Zagorodniy N.V., Malik B.K. Karagandinskiy metod dvukhetapnoy revizii kolennogo sustava pri periproteznoy infektsii: sbornik k 25-letiyu kafedry TiO RUDN [Karaganda method of two-stage revision of the knee joint in case of periprosthetic infection: a collection for the 25th anniversary of the Department of T&E RUDN], 2017. Pp. 362–369.
5. Kurtz S.M., Lau E., Watson H., Schmier J.K., Parvizi J. Economic burden of periprosthetic joint infection in the United States. J. Arthroplast., 2012, vol. 27, pp. 61–65. e1. DOI: 10.1016/j.arth.2012.02.022
6. Hung C.H., Ko J.Y., Liao P.S., Yeh C.W., Hsu C.C., Lin M.C., Hsu H.C., Kuo S.J. Epidemiology of fatal/non-fatal suicide among patients with chronic osteomyelitis (COM): a nationwide population-based study. The Journal of international medical research, 2020, vol. 48 (6). DOI: 10.1177/0300060520919238
7. Peltola H., Pääkkönen M., Kallio P., Kallio M.J., Group O-SAS. Short-versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases. Pediatr. Infect. Dis. J., 2010, vol. 29, pp. 1123–1128. DOI: 10.1097/INF.0b013e3181f55a8
8. Hong D.K., Gutierrez K. Osteomyelitis In: Long SS, Prober CG, Fischer M, eds. Principles and Practice of Pediatric Infectious Diseases. 5th ed. Philadelphia, PA: Elsevier, 2018. Pp. 480–486.
9. Peltola H., Pääkkönen M. Acute osteomyelitis in children. N Engl J Med. 2014, Jan 23. Vol. 370 (4). Pp. 352–360. DOI: 10.1056/NEJMra1213956
10. Arnold S.R., Elias D., Buckingham S.C. et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop, 2006, Nov-Dec, vol. 26 (6), pp. 703–708. DOI: 10.1097/01.bpo.0000242431.91489.b4
11. Weiss-Salz I., Yagupsky P. Kingella kingae infections in children: an update. In: Curtis N., Finn A., Pollard A.J., eds. Hot Topics in Infection and Immunity in Children VIII: Advances in Experimental Medicine and Biology. New York, NY: Springer, 2012. Vol. 719. Pp. 67–80.
12. Weichert S., Sharland M., Clarke N.M., Faust S.N. Acute haematogenous osteomyelitis in children: is there any evidence for how long we should treat? Curr Opin Infect Dis, 2008, Jun, vol. 21 (3), pp. 258–262. DOI: 10.1097/QCO.0b013e3283005441. PMID: 18448970.
13. Federal’nye klinicheskie rekomendatsii. Ostryy gematogennyy osteomielit u detey, pod red. A.Yu. Razumovskogo [Federal clinical guidelines. Acute hematogenous osteomyelitis in children. Ed. by A.Yu. Razumovsky]. Voronezh, 2015.
14. Perlman M.H., Patzakis M.J., Kumar P.J., Holtom P. The incidence of joint involvement with adjacent osteomyelitis in pediatric patients. J Pediatr Orthop, 2000, Jan-Feb, vol. 20 (1), pp. 40–43. PMID: 10641686.
15. Offiah A.C. Acute osteomyelitis, septic arthritis and discitis: differences between neonates and older children. Eur J Radiol, 2006, vol. 60 (2), pp. 221–232. DOI: 10.1016/j.ejrad.2006.07.016
16. Iliadis A.D., Ramachandran M. Paediatric bone and joint infections. EFORT Open Rev., 2017, Mar 13, vol. 2 (1), pp. 7–12. DOI: 10.1302/2058-5241.2.160027
17. Arnold J.C., Bradley J.S. Osteoarticular Infections in Children. Infect Dis Clin North Am, 2015, Sep, vol. 29 (3), pp. 557–574. DOI: 10.1016/j.idc.2015.05.012. PMID: 26311358.
18. Yeo A., Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ, 2014, Jan 20, vol. 348, p. g66. DOI: 10.1136/bmj.g66
19. Pääkkönen M., Peltola H. Acute osteomyelitis in children. N Engl J Med, 2014, Apr 3, vol. 370 (14), pp. 1365–1366. DOI: 10.1056/NEJMc1402234. PMID: 24693913.
20. Thein R., Tenenbaum S., Chechick O., Leshem E., Chechik A., Liberman B. Delay in diagnosis of femoral hematogenous osteomyelitis in adults: an elusive disease with poor outcome. Isr Med Assoc J, 2013, Feb, vol. 15 (2), pp. 85–88. PMID: 23516768.
21. Kremers H.M., Nwojo M.E., Ransom J.E., Wood-Wentz C.M., Melton L.J. 3rd, Huddleston PM 3rd. Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009. J Bone Joint Surg Am, 2015, vol. 97 (10), pp. 837–845. DOI: 10.2106/JBJS.N.01350
22. Saginova D.A. Local use of biodegradable materials in the treatment of chronic osteomyelitis. Vestnik KazNMU, 2018, no. 1 (in Russ.).
23. Kronig I., Vaudaux P., Suvà D., Lew D., Uçkay I. Acute and chronic osteomyelitis. In Clinical Infectious Disease, 2015. 2nd edn. Pp. 448–453. DOI: 10.1017/CBO9781139855952.080
24. Tsukayama T.D., Estrada R., Gustilo R.B. Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections. J. Bone. Joint. Surg. Am., 1996, vol. 78, pp. 512–523. DOI: 10.2106/00004623-199604000-00005
25. Hotchen A.J., McNally M.A., Sendi P. The classification of long bone osteomyelitis: a systemic review of the literature. J. Bone Jt. Infect., 2017, vol. 2, p. 167. DOI: 10.7150/jbji.21050
26. Cierny Iii G., Mader J.T., Penninck J.J. The classic: a clinical staging system for adult osteomyelitis. Clin. Orthop. Relat. Res., 2003, vol. 414, pp. 7–24. DOI: 10.1097/01.blo.0000088564.81746.62
27. Waldvogel F.A., Medoff G., Swartz M.N. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. New Engl. J. Med., 1970, vol. 282, pp. 260–266. DOI: 10.1056/NEJM197001292820507
28. Wu H., Shen J., Yu X. et al. Two stage management of Cierny- Mader type IV chronic osteomyelitis of the long bones. Injury, 2017, vol. 48, pp. 511–518. DOI: 10.1016/j.injury.2017.01.007
29. Zimmermann P., Curtis N. The role of Cutibacterium acnes in auto-inflammatory bone disorders. Eur J Pediatr, 2019, vol. 178 (1), pp. 89–95. DOI: 10.1007/s00431-018-3263-2
30. Kocher M.S., Zurakowski D., Kasser J.R. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. J Bone Joint Surg Am, 1999, vol. 81-A, pp. 1662–1670. DOI: 10.2106/00004623-199912000-00002
31. Fragío Gil J.J., González Mazarío R., Salavert Lleti M., Román Ivorra J.A. Vertebral osteomyelitis: Clinical, microbiological and radiological characteristics of 116 patients. Med Clin (Barc), 2020, Oct 23, vol. 155 (8), pp. 335–339. English, Spanish. DOI: 10.1016/j.medcli.2019.12.029. Epub 2020 May 21. PMID: 32446680.
32. Kavanagh N., Ryan E.J., Widaa A., Sexton G., Fennell J., O’Rourke S., Cahill K.C., Kearney C.J., O’Brien F.J., Kerrigan S.W. Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions. Clin Microbiol Rev, 2018, Feb 14, vol. 31 (2), p. e00084-17. DOI: 10.1128/CMR.00084-17. PMID: 29444953; PMCID: PMC5967688.
33. Beaman F.D., von Herrmann P.F., Kransdorf M.J., Adler R.S., Amini B., Appel M., Arnold E., Bernard S.A., Greenspan B.S., Lee K.S., Tuite M.J., Walker E.A., Ward R.J., Wessell D.E., Weissman B.N. ACR Appropriateness Criteria(R) Suspected Osteomyelitis, Septic Arthritis, or Soft Tissue Infection (Excluding Spine and Diabetic Foot). J Am Coll Radiol, 2017, vol. 14, pp. S326–S337. PMID: 28473089.
34. Palestro C.J., Love C., Miller T.T. Infection and musculoskeletal conditions: Imaging of musculoskeletal infections. Best Pract Res Clin Rheumatol, 2006, Dec, vol. 20 (6), pp. 1197–1218. DOI: 10.1016/j.berh.2006.08.009 PMID: 17127204.
35. Miyazaki O., Tanaka T., Aoki H. et al. Acute hematogenous pelvic osteomyelitis: appropriate timing for MRI [published online ahead of print, 2020 Jun 19]. Pediatr Int., 2020, vol. 10, p. 1111/ped.14353. DOI: 10.1111/ped.14353
36. Kapoor A., Page S., Lavalley M., Gale D.R., Felson D.T. Magnetic resonance imaging for diagnosing foot osteomyelitis: a meta-analysis. Arch Intern Med, 2007, Jan 22, vol. 167 (2), pp. 125–132. DOI: 10.1001/archinte.167.2.125. PMID: 17242312.
37. Ergen F.B. Sanverdi S.E., Oznur A. Charcot foot in diabetes and an update on imaging. Diabet Foot Ankle, 2013, vol. 4. DOI: 10.3402/dfa.v4i0.21884
38. Khawaja A.Z., Cassidy D.B., Al Shakarchi J., McGrogan D.G., Inston N.G., Jones R.G. Revisiting the risks of MRI with Gadolinium based contrast agents-review of literature and guidelines. Insights Imaging, 2015, Oct, vol. 6 (5), pp. 553–558. DOI: 10.1007/s13244-015-0420-2. Epub 2015 Aug 8. PMID: 26253982; PMCID: PMC4569598.
39. McDonald R.J., McDonald J.S., Kallmes D.F., Jentoft M.E., Murray D.L., Thielen K.R., Williamson E.E., Eckel L.J. Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. Radiology, 2015, vol. 275 (3), pp. 772–782. DOI: 10.1148/radiol.15150025. Epub 2015 Mar 5. PMID: 25742194.
40. Langsjoen J., Neuwelt A., Eberhardt S. et al. A comparison of ferumoxytol with gadolinium as contrast agents for the diagnostic magnetic resonance imaging of osteomyelitis [published online ahead of print, 2020 May 19]. Magn Reson Imaging, 2020, vol. 71, pp. 45–54. DOI:10.1016/j.mri.2020.04.012
41. Jennin F., Bousson V., Parlier C. et al. Bony sequestrum: a radiologic review. Skelet Radiol, vol. 40, pp. 963–975. DOI: 10. 1007/s00256-010-0975-4
42. Chai J.W., Hong S.H., Choi J-Y. et al. Radiologic diagnosis of osteoid osteoma: from simple to challenging findings. Radiographics, 2010, vol. 30, pp. 737–749. DOI: 10.1148/rg.303095120
43. Amsilli M., Epaulard O. How is the microbial diagnosis of bacterial vertebral osteomyelitis performed? An 11-year retrospective study [published online ahead of print, 2020 Jun 26. Eur J Clin Microbiol Infect Dis, 2020, vol. 10. DOI: 10.1007/s10096-020-03929-1
44. Bori G., McNally M.A., Athanasou N. Histopathology in Periprosthetic Joint Infection: When Will the Morphomolecular Diagnosis Be a Reality?  Biomed Res Int., 2018, May 13. DOI:10.1155/2018/1412701
45. Lonner J.H., Desai P., Dicesare P.E., Steiner G., Zuckerman J.D. The reliability of analysis of intraoperative frozen sections for identifying active infection during revision hip or knee arthroplasty. JBJS, 1996, vol. 78, pp. 1553–1558. DOI: 10.2106/00004623-199610000-00014
46. Feldman D.S., Lonner J.H., Desai P.M., Zuckerman J.D. The role of intraoperative frozen sections in revision total joint arthroplasty. JBJS, 1995, vol. 77, pp. 1807–1813. DOI: 10.2106/00004623-199512000-00003
47. Athanasou N., Pandey R., De S.teiger R., Crook D., Smith P.M. Diagnosis of infection by frozen section during revision arthroplasty. J. Bone Jt. Surg. Br, 1995, vol. 77, pp. 28–33. DOI: 10.1302/0301-620X.77B1.7822391
48. Masters E.A. et al. An in vitro platform for elucidating the molecular genetics of S. aureus invasion of the osteocyte lacuno-canalicular network during chronic osteomyelitis. Nanomed. Nanotechnol. Biol. Med., 2019. DOI: 10.1016/j.nano.2019.102039
49. Hellebrekers P., Rentenaar R.J., McNally M.A. et al. Getting it right first time: The importance of a structured tissue sampling protocol for diagnosing fracture-related infections. Injury, 2019, vol. 50 (10), pp. 1649–1655. DOI:10.1016/j.injury.2019.05.014
50. Calleja R., Kabashneh S. Acute Myeloid Leukemia: A «Head to Toe» Examination. Cureus, 2020, vol. 12 (6), pp. e8526. DOI:10.7759/cureus.8526
51. McCarville M.B., Chen J.Y., Coleman J.L., Li Y., Li X., Adderson E.E., Neel M.D., Gold R.E., Kaufman R.A. Distinguishing Osteomyelitis From Ewing Sarcoma on Radiography and MRI. AJR. American journal of roentgenology, 2015, vol. 205 (3), pp. 640–651. DOI: 10.2214/AJR.15.14341
52. Congedi S., Minotti C., Giaquinto C., Da Dalt L., Donà D. Acute infectious osteomyelitis in children: new treatment strategies for an old enemy. World J Pediatr., 2020. DOI: 10.1007/s12519-020-00359-z
53. Liu R.W., Abaza H., Mehta P. et al. Intravenous versus oral outpatient antibiotic therapy for pediatric acute osteomyelitis. Iowa Orthop J, 2013, vol. 33, pp. 208–212. PMID: 24027485.
54. Messina A.F., Namtu K., Guild M., Dumois J.A., Berman D.M. Trimethoprim-sulfamethoxazole therapy for children with acute osteomyelitis. Pediatr Infect Dis J, 2011, Dec, vol. 30 (12), pp. 1019–1021. DOI: 10.1097/INF.0b013e31822db658. PMID: 21817950.
55. Peltola H., Pääkkönen M., Kallio P., Kallio M.J. OM-SA Study Group. Clindamycin vs. first-generation cephalosporins for acute osteoarticular infections of childhood a prospective quasi-randomized controlled trial. Clin Microbiol Infect, 2012, vol. 18, pp. 582–589.
56. McNeil J.C., Kaplan S.L., Vallejo J.G. The influence of the route of antibiotic administration, methicillin susceptibility, vancomycin duration and serum trough concentration on outcomes of pediatric Staphylococcus aureus bacteremic osteoarticular infection. Pediatr Infect Dis J, 2017, vol. 36, pp. 572–577.
57. Roul-Levy A., Looten V., Bachy M. et al. Oral Ambulatory Treatment of Acute Osteomyelitis in Children: A Case-Control Study. Pediatr Emerg Care, 2016, vol. 32 (3), pp. 154–156. DOI: 10.1097/PEC.0000000000000725. PMID: 26928094.
58. Keren R., Shah S.S., Srivastava R. et al; Pediatric Research in Inpatient Settings Network. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr, 2015, vol. 169 (2), pp. 120–128. DOI: 10.1001/jamapediatrics.2014.2822. PMID: 25506733.
59. Li H.K., Rombach I., Zambellas R. et al; OVIVA Trial Collaborators. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med, 2019, vol. 380 (5), pp. 425–436. DOI: 10.1056/NEJMoa1710926. PMID: 30699315; PMCID: PMC6522347.
60. Yipp B.G. et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat. Med., 2012, vol. 18, pp. 1386–1393. DOI: 10.1038/nm.2847
61. Cheung G.Y., Otto M. The potential use of toxin antibodies as a strategy for controlling acute Staphylococcus aureus infections. Expert Opin. Ther. Targets, 2012, vol. 16, pp. 601–612. DOI: 10.1517/14728222.2012.682573
62. Huang C.Y, Hsieh R.W., Yen H.T., Hsu T.C., Chen C.Y., Chen Y.C., Lee C.C. Short- versus long-course antibiotics in osteomyelitis: A systematic review and meta-analysis. Int J Antimicrob Agents, 2019, vol. 53 (3), pp. 246–260. DOI: 10.1016/j.ijantimicag.2019.01.007. Epub 2019 Jan 10. PMID: 30639627.
63. Kim H.K., Thammavongsa V., Schneewind O., Missiakas D. Recurrent infections and immune evasion strategies of Staphylococcus aureus. Curr. Opin. Microbiol., 2012, vol. 15, pp. 92–99. DOI: 10.1016/j.mib.2011.10.012
64. Bernard L., Dinh A., Ghout I. et al; Duration of Treatment for Spondylodiscitis (DTS) study group. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. The Lancet, 2015, vol. 385, pp. 875–882. DOI: 10.1016/S0140-6736(14)61233-2
65. Tone A., Nguyen S., Devemy F. et al. Six-week versus twelve-week antibiotic therapy for non surgically treated diabetic foot osteomyelitis: a multicenter open label controlled randomized study. Diabetes Care, 2015, vol. 38, pp. 302–307. DOI: 10.2337/dc14-1514
66. Park K.H., Cho O.H., Lee J.H. et al. Optimal duration of antibiotic therapy in patients with hematogenous vertebral osteomyelitis at low risk and high risk of recurrence. Clin Infect Dis, 2016, vol. 62, pp. 1262–1669. DOI: 10.1093/cid/ciw098.