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Alendronate enhances antibiotic-impregnated bone grafts in the treatment of osteomyelitis

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Abstract

Bisphosphonates are systemic drugs. There is limited knowledge about their effects when applied locally and in osteomyelitis treatment. A prospective longitudinal randomised controlled study was designed in rat tibia to test the efficacy of local or systemically administered bisphosphonates for controlling the osteolytic reactions and possible effects on local infection control. Tibial osteomyelitis was induced in 72 Wistar albino rats with Staphylococcus aureus ATCC 25923 strain. Débridement was performed on all rats in all groups. No other treatment was given to the control group. Treatment groups received “plain bone grafts”, “vancomycin-loaded bone grafts”, “vancomycin-loaded bone grafts+systemic alendronate”, “alendronate-impregnated bone grafts” and “vancomycin+alendronate-impregnated grafts”. Study results were evaluated by swab cultures, radiology, quantitative computed tomography, dual-energy X-ray absorptiometry (DEXA) and histopathology. S. aureus was eradicated in groups II and IV by the sixth week. Diaphyseal widening, bone deformation, diaphyseal widening and osteolysis scores were significantly lower (p < 0.05), and bone mineral content, density measurements and DEXA scores were significantly higher (p = 0.001) with alendronate administration. Histology revealed marked osteoblastic activity. Local alendronate interfered with local infection control. Even though local alendronate at the given dose has stronger effects, the possible effects on the local inflammatory process needs to be clarified.

Résumé

Les Bisphosphonates sont des médicaments utilisés par voie systémique avec un effet systémique. Nous n’avons aucune connaissance sur leurs effets lorsqu’ils sont utilisés localement, notamment dans le traitement de l’ostéomyélite. Une étude prospective longitudinale randomisée a été réalisée sur le tibia de rat afin de tester l’efficacité de l’administration systémique ou locale des bisphosphonates sur les réactions ostéolytiques et sur de possibles effets sur une infection locale. L’ostéomyélite tibiale a été induite chez 72 rats albinos Wistar avec une inoculation d’un staphylocoque Aureus ATCC 25923. Une mise à plat a été réalisée chez tous les rats, dans tous les groupes. Il n’y a pas eu d’autres traitements dans le groupe contrôle. Les autres groupes ont reçu une greffe osseuse, soit une greffe osseuse imprégnée de vancomycine soit une greffe osseuse imprégnée de vancomycine et avec injection systémique d’alendronate, soit une greffe osseuse imprégnée d’alendronate et enfin une greffe osseuse imprégnée d’alendronate et de vancomycine. Les résultats ont été évalués par cultures bactériologiques, radio, QCT, DEXA et histopathologie. Le staphylocoque doré a été éradiqué dans les groupes II et IV après six semaines. Le gonflement diaphysaire, la déformation osseuse et l’élargissement diaphysaire avec lésions ostéolytiques ont été de façon significative diminués (p < 0.05), de même que la densité minérale osseuse et le score DEXA ont été significativement plus élevés (p = 0.001) ceci grâce à l’administration de l’alendronate. L’examen histologique a mis en évidence une activité ostéoblastique et l’on peut affirmer que l’administration locale d’alendronate a une influence sur une infection locale. Cependant, l’alendronate administré localement peut avoir des effets importants au niveau du processus inflammatoire qu’il faudra étudier secondairement.

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Acknowledgement

The authors thank Prof. Dr. M.C. Avunduk, Selcuk University, Faculty of Medicine, Dept. of Pathology for his kind help in histological assessment and Merck Research Laboratories, Merck & Co., Inc, Rathway, NJ, USA for kindly supplying alendronate and financial support for the project. The above-mentioned company was not involved in planning the experiment and did not take part in data collection, analyses, interpretation or writing of the manuscript.

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Authors and Affiliations

  1. 5th Orthopaedics and Traumatology Clinic, Ankara Numune Research and Training Hospital, Altindag, 06100, Ankara, Turkey

    Akif Muhtar Ozturk, Abdullah Yalcin Tabak, Cem Nuri Aktekin & Murat Altay

  2. Department of Histology and Embryology, Ankara University, Faculty of Medicine, 06100, Ankara, Turkey

    Esra Erdemli & Sercin Karahuseyinoglu

  3. Middle East Technical University, Medical Center, 06531, Ankara, Turkey

    Feza Korkusuz

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  1. Akif Muhtar Ozturk
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  2. Abdullah Yalcin Tabak
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Correspondence to Akif Muhtar Ozturk.

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Ozturk, A.M., Tabak, A.Y., Aktekin, C.N. et al. Alendronate enhances antibiotic-impregnated bone grafts in the treatment of osteomyelitis. International Orthopaedics (SICO 32, 821–827 (2008). https://doi.org/10.1007/s00264-007-0396-8

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  • DOI: https://doi.org/10.1007/s00264-007-0396-8

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