Osteoclastic Bone Resorption in Chronic Osteomyelitis PhD thesis Kirill Gromov Faculty of Health Sciences University of Aarhus Denmark 2009 2 From Orthopaedic Research Laboratory Department of Orthopaedics Aarhus University Hospital Aarhus Denmark Osteoclastic Bone Resorption in Chronic Osteomyelitis PhD thesis Kirill Gromov Faculty of Health Sciences University of Aarhus Denmark 2009 3 Table of Contents PhD and Doctoral Theses from the Orthopaedic Research Group ......................... 5 List of Papers ..........................................................................................................................10 Supervisors .............................................................................................................................11 Preface and acknowledgements ......................................................................................12 Abstract in Danish.................................................................................................................13 Abstract ....................................................................................................................................15 List of abbreviations: ...........................................................................................................17 1 Introduction ........................................................................................................................18 2 Osteomyelitis background: etiology, causes and treatment...............................20 2.1 Pathology....................................................................................................................................21 2.2 Diagnosis ....................................................................................................................................23 2.3 Treatment...................................................................................................................................24 2.3.1 Prophylaxis...........................................................................................................................................24 2.3.2 Medical ...................................................................................................................................................25 2.3.3 Surgical...................................................................................................................................................25 2.4 Emergence of methicillin­resistant S. aureus.................................................................25 2.5 Multidrug resistant Acinetobacter in warfare..............................................................26 2.6 Bisphosphonates......................................................................................................................27 2.7 Osteonecrosis of the jaw (ONJ)............................................................................................29 2.8 Animal models of osteomyelitis..........................................................................................31 2.8.1 Bacterial species and inoculation ...............................................................................................31 2.8.2 Inoculation routes and infection promoters..........................................................................32 2.8.3 Animals...................................................................................................................................................33 3 Problems and main goals of the study........................................................................36 3.1 Animal models. .........................................................................................................................36 3.2 Osteomyelitis and use of bisphosphonates.....................................................................36 3.3 Multi­drug resistant Acinetobacter species ....................................................................37 4 Materials and methods ....................................................................................................37 4.1 strains, pathogenic challenge and surgical procedure ............................................37 4.2 Histology.....................................................................................................................................40 4.3 DNA purification and nuc/b­actin RTQ­PCR ...................................................................40 4.4 In vivo bioluminescent imaging ..........................................................................................42 4.5 Drug treatments.......................................................................................................................44 4.6 Antibiotic prophylaxis ...........................................................................................................45 5 Results...................................................................................................................................47 5.1 Study I ..........................................................................................................................................47 5.2 Study 2 .........................................................................................................................................47 5.3 Study 3 .........................................................................................................................................48 4 6 Discussion ............................................................................................................................49 6.1 Model ...........................................................................................................................................49 6.2 Anti­catabolic treatment .......................................................................................................51 6.3 Prophylactic antibiotic treatment......................................................................................52 7 Concluding remarks and future perspectives..........................................................54 References ...............................................................................................................................55 Paper I…………………………………..…………………………………………………………Appendix I Paper II…………………………………..…………………………………………………....…Appendix II Paper III…………………………………..……………………………………………………Appendix III 5 PhD and Doctoral Theses from the Orthopaedic Research Group www.orthoresearch.dk, University Hospital of Aarhus, Denmark PhD Theses 1. Polyethylene Wear Analysis. Experimental and Clinical Studies in Total Hip Arthroplasty. Maiken Stilling, June 2009 www.statsbiblioteket.dk 2. Surgical Advances in Periacetabular Osteotomy for Treatment of Hip Dysplasia in Adults Anders Troelsen, March 2009 Acta Orthopaedica (Suppl 332) 2009;80 3. The Influence of Local Bisphosphonate Treatment on Implant Fixation Thomas Vestergaard Jakobsen, December 2008 www.statsbiblioteket.dk 4. Adjuvant therapies of bone graft around non-cemented experimental orthopaedic implants. Stereological methods and experiments in dogs Jørgen Baas, July 2008 Acta Orthopaedica (Suppl 330) 2008;79 5. CoCrMo alloy, in vitro and in vivo studies Stig Storgaard Jakobsen, June 2008 www.statsbiblioteket.dk 6 6. Rehabilitation outcome after total hip replacement; prospective randomized studies evaluating two different postoperative regimes and two different types of implants Mette Krintel Petersen, June 2008 www.statsbiblioteket.dk 7. Efficacy, effectiveness, and efficiency of accelerated perioperative care and rehabilitation intervention after hip and knee arthroplasty Kristian Larsen, May 2008 www.statsbiblioteket.dk 8. Rehabilitation of patients aged over 65 years after total hip replacement - based on patients’ health status Britta Hørdam, February 2008 www.statsbiblioteket.dk 9. Evaluation of Bernese periacetabular osteotomy; Prospective studies examining projected load-bearing area, bone density, cartilage thickness and migration Inger Mechlenburg, August 2007 Acta Orthopaedica (Suppl 329) 2008;79 10. Combination of TGF-β1 and IGF-1 in a biodegradable coating. The effect on implant fixation and osseointegration and designing a new in vivo model for testing the osteogenic effect of micro-structures in vivo Anders Lamberg, June 2007 www.statsbiblioteket.dk 11. On the longevity of cemented hip prosthesis and the influence on implant design Mette Ørskov Sjøland, April 2007 www.statsbiblioteket.dk 12. Reaming procedure and migration of the uncemented acetabular component in total hip replacement Thomas Baad-Hansen, February 2007 7 www.statsbiblioteket.dk 13. Studies based on the Danish Hip Arthroplasty Registry Alma B. Pedersen, 2006 www.statsbiblioteket.dk 14. DEXA-scanning in description of bone remodeling and osteolysis around cementless acetabular cups Mogens Berg Laursen, November 2005 www.statsbiblioteket.dk 15. Biological response to wear debris after total hip arthroplasty using different bearing materials Marianne Nygaard, June 2005 www.bibliotek.dk 16. The influence of RGD peptide surface modification on the fixation of orthopaedic implants Brian Elmengaard, December 2004 www.statsbiblioteket.dk 17. Stimulation and substitution of bone allograft around non-cemented implants Thomas Bo Jensen, October 2003 www.statsbiblioteket.dk 18. Surgical technique's influence on femoral fracture risk and implant fixation. Compaction versus conventional bone removing techniques Søren Kold, January 2003 www.statsbiblioteket.dk