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The Efficacy of Boric Acid Used to Treat Experimental Osteomyelitis Caused by Methicillin-Resistant Staphylococcus aureus: an In Vivo Study

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Abstract

We explored the ability of local and systemic applications of boric acid (BA) to reduce the numbers of methicillin-resistant Staphylococcus aureus (MRSA) in a rat model of tibial osteomyelitis (OM), and compared boric acid with vancomycin (V). Implant-associated osteomyelitis was established in 35 rats. After 4 weeks, at which time OM was evident both radiologically and serologically in all animals, the rats were divided into five groups of equal number: group 1, control group (no local application of BA or other medication); group 2, V group; group 3, local BA + V group; group 4, local BA group; and group 5, local + systemic BA group. Serum total antioxidant status, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, were measured. Pathological changes attributable to bone OM were evaluated using a grading system. Bacterial colony-forming units (CFUs) per gram of bone were counted. The lowest bacterial numbers were evident in group 3, and the bacterial numbers were significantly lower than that of the control group in all four test groups (p < 0.001). Group 3 also had the least severe bone infection (OM score 1.7 ± 1.1, p < 0.05). Upon histological and microbiological evaluation, no significant difference was evident between groups 2 and 3. Total antioxidant levels were significantly different in all treatment groups compared to the control group. Microbiological and histopathological evaluation showed that systemic or local application of BA was effective to treat OM, although supplementary V increased the effectiveness of BA.

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References

  1. Parsons B, Strauss E (2004) Surgical management of chronic osteomyelitis. Am J Surg 188(Suppl):57–66

    Article  PubMed  Google Scholar 

  2. Tice AD, Hoaglund PA, Shoultz DA (2003) Outcomes of osteomyelitis among patients treated with outpatient parenteralantimicrobial therapy. Am J Med 114:723–728

    Article  CAS  PubMed  Google Scholar 

  3. Steinkraus G, White R, Friedrich L (2007) Vancomycin MIC creep in nonvancomycin- intermediate Staphylococcus aureus (VISA), vancomycin susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001–05. J Antimicrob Chemother 60:788–794

    Article  CAS  PubMed  Google Scholar 

  4. Sener M, Kazimoglu C, Karapinar H et al (2010) Comparison of various surgical methods in the treatment of implant-related infection. Int Orthop 34(3):419–423

    Article  PubMed  Google Scholar 

  5. Garcia EJ, Sieg RN, Abdelgawad AA (2013) Localapplication of freeantibioticpowder in the treatment of osteomyelitis in a rat model. Orthopedics 36(8):e986–e989

    Article  PubMed  Google Scholar 

  6. Gölge UH, Kaymaz B, Arpaci R, Kömürcü E, Göksel F, Güven M, Güzel Y, Cevizci S (2015) Effects of boric acid on fracture healing: an experimental study. Biol Trace Elem Res 167(2):264–271

    Article  PubMed  Google Scholar 

  7. Kömürcü E, Özyalvaçlı G, Kaymaz B, Gölge UH, Göksel F, Cevizci S, Adam G, Ozden R (2015) Effects of local administration of boric acid on posterolateral spinal fusion with autogenous bone grafting in a rodent model. Biol Trace Elem Res 167(1):77–83

    Article  PubMed  Google Scholar 

  8. Hakki SS, Bozkurt BS, Hakki EE (2010) Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1). J Trace Elem Med Biol 24:243–250

    Article  CAS  PubMed  Google Scholar 

  9. Zeron Mullins M, Trouton KM (2015) BASIC study: is intravaginal boric acid non-inferior to metronidazole in symptomatic bacterial vaginosis? Study protocol for a randomized controlled trial. Trials 16:315

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lefebvre MA, Quach C, Daniel SJ (2015) Chronic suppurative otitis media due to nontuberculous mycobacteria: a case of successful treatment with topical boric acid. Int J Pediatr Otorhinolaryngol 79(7):1158–1160

    Article  PubMed  Google Scholar 

  11. Borrelly J, Blech MF, Grosdidier G, Martin-Thomas C, Hartemann P (1991) Contribution of a 3% solution of boric acid in the treatment of deep wounds with loss of substance. Ann Chir Plast Esthet 36(1):65–69

    CAS  PubMed  Google Scholar 

  12. Lucke M, Schmidmaier G, Sadoni S, Wildemann B, Schiller R, Stemberger A, Haas NP, Raschke M (2003) A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B Appl Biomater 67(1):593–602

    Article  CAS  PubMed  Google Scholar 

  13. Petty W, Spanier S, Shuster JJ, Silverthorne C (1985) The influence of skeletal implants on incidence of infection. Experiments in a canine model. J Bone Joint Surg Am 67:1236–1244

    CAS  PubMed  Google Scholar 

  14. Petty W, Spanier S, Shuster JJ (1988) Prevention of infection after total joint replacement. Experiments with a canine model. J Bone Joint Surg 70A:536–539

    Google Scholar 

  15. Cierny G, Mader JT (1984) Adult chronic osteomyelitis. Orthopedics 7:1557–1564

    CAS  PubMed  Google Scholar 

  16. Lima AL, Oliveira PR, Carvalho VC, Cimerman S, Savio E (2014) Diretrizes Panamericanas para el Tratamiento de las Osteomielitis e Infecciones de Tejidos Blandos Group. Recommendations for the treatment of osteomyelitis. Braz J Infect Dis 18(5):526–534

    Article  PubMed  Google Scholar 

  17. Landersdorfer CB, Bulitta JB, Kinzig M, Holzgrabe U, Sörgel F (2009) Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamic and bioanalytical considerations. ClinPharmacokinet 48:89–124

    Article  CAS  Google Scholar 

  18. Stengel D, Bauwens K, Sehouli J, Ekkernkamp A, Porzsolt F (2001) Systematic review and meta-analysis of antibiotic therapy forbone and joint infections. Lancet Infect Dis 1:175–188

    Article  CAS  PubMed  Google Scholar 

  19. The current status of material used for depot delivery of drugs (2004) Clin Orthop Relat Res 427: 72–78.

  20. Li GY, Yin JM, Ding H, Jia WT, Zhang CQ (2013) Efficacy of leukocyte- and platelet-richplasmagel (L-PRPgel) in treating osteomyelitis in a rabbit model. J Orthop Res 31(6):949–956

    Article  CAS  PubMed  Google Scholar 

  21. Mader JT, Guckian JC, Glass DL, Reinarz JA (1978) Therapy with hyperbaric oxygen for experimental osteomyelitis due to Staphylococcus aureus in rabbits. J Infect Dis 138:312–318

    Article  CAS  PubMed  Google Scholar 

  22. Mader JT, Brown GL, Guckian JC, Wells CH, Reinarz JA (1980) A mechanism for the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits. J Infect Dis 142:915–922

    Article  CAS  PubMed  Google Scholar 

  23. Fang RC, Galiano RD (2009) Adjunctivetherapies in the treatment of osteomyelitis. Semin Plast Surg 23(2):141–147

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chen CE, Shih ST, Fu TH, Wang JW, Wang CJ (2003) Hyperbaric oxygen therapy in the treatment of chronic refractory osteomyelitis: a preliminary report. Chang Gung Med J 26:114–121

    PubMed  Google Scholar 

  25. Chen CE, Ko JY, Fu TH, Wang CJ (2004) Results of chronic osteomyelitis of the femur treated with hyperbaric oxygen: a preliminary report. Chang Gung Med J 27:91–97

    PubMed  Google Scholar 

  26. Chen X, Kidder LS, Lew WD (2002) Osteogenic protein-1 induced bone formation in an infected segmental defect in the rat femur. J Orthop Res 20:142–150

    Article  CAS  PubMed  Google Scholar 

  27. Chen X, Schmidt AH, Tsukayama DT, Bourgeault CA, Lew WD (2006) Recombinant human osteogenic protein-1 induces bone formation in a chronically infected, internally stabilized segmental defect in the rat femur. J Bone Joint Surg Am 88:1510–1523

    Article  PubMed  Google Scholar 

  28. Kose N, Otuzbir A, Pekşen C, Kiremitçi A, Doğan A (2013) A silver ion-doped calcium phosphate-based ceramic nanopowder-coated prosthesis increased infection resistance. Clin Orthop Relat Res 471(8):2532–2539

    Article  PubMed  PubMed Central  Google Scholar 

  29. Marx RE, Ehler WJ, Tayapongsak P, Pierce LW (1990) Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 160:519–524

    Article  CAS  PubMed  Google Scholar 

  30. Benderdour M, Hess K, Dzondo-Gadet M, Nabet P, Belleville F, Dousset B (1998) Boron modulates extracellular matrix and TNF alpha synthesis in human fibroblasts. Biochem Biophys Res Commun 246(3):746–751

    Article  CAS  PubMed  Google Scholar 

  31. Gorustovich AA, Steimetz T, Nielsen FH, Guglielmotti MB (2008) A histomorphometric study of alveolar bone modelling and remodelling in mice fed a boron-deficient diet. Arch Oral Biol 53(7):677–682

    Article  CAS  PubMed  Google Scholar 

  32. Ying X, Cheng S, WangW LZ, Chen Q, ZhangW KD, Shen Y, Cheng X, Rompis FA, Peng L, Zhu Lu C (2011) Effect of boron on steogenic differentiation of human bone marrow stromal cells. Biol Trace Elem Res 144(1–3):306–315

    Article  CAS  PubMed  Google Scholar 

  33. Schmidt M, Schaumberg JZ, Steen CM, Boyer MP (2010) Boric acid disturbs cell wall synthesis in Saccharomyces cerevisiae. Int J Microbiol 2010:930465

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sheehy SH, Atkins BA, Bejon P et al (2010) The microbiology of chronic osteomyelitis: prevalence of resistance to common empirical anti-microbial regimens. J Infect 60:338–343

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

No benefits in any form have been or will be receivedfroma commercial party related directly or indirectly to the subjectof this manuscript. The authors thank Havva ERDEM ( associated professor, MD, in Ordu University Medical School, Pathology Department) for contributions to hystopathological evaluation.

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Correspondence to Yunus Güzel.

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Our study protocol was approved by the Animal Welfare Committee of the Medical University of Canakkale Onsekiz Mart, Canakkale, Turkey.

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There are no conflicts of interest related to the manuscript. No funds were received in support of this study.

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Güzel, Y., Golge, U.H., Goksel, F. et al. The Efficacy of Boric Acid Used to Treat Experimental Osteomyelitis Caused by Methicillin-Resistant Staphylococcus aureus: an In Vivo Study. Biol Trace Elem Res 173, 384–389 (2016). https://doi.org/10.1007/s12011-016-0662-y

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  • DOI: https://doi.org/10.1007/s12011-016-0662-y

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