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Joint German Congress of Orthopaedics and Trauma Surgery

02. - 06.10.2006, Berlin

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Erythropoietin (EPO) - EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing

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  • J.H. Holstein - Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
  • M.D. Menger - Institut für klinisch-experimentelle Chirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
  • C. Meier - Klinik für Unfallchirurgie, Universitätsspital Zürich, Zürich, Switzerland
  • U. Culemann - Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
  • R.J. Wirbel - Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
  • T. Pohlemann - Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 02.-06.10.2006. Düsseldorf, Köln: German Medical Science; 2006. DocE.4.1-248

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgu2006/06dgu0108.shtml

Published: September 28, 2006

© 2006 Holstein et al.
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Outline

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Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunochistochemical and biomechanical analysis. Thirty-two SKH1-hr mice were treated by daily i.p. injections of 5000U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6±19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5±7.1%) when compared to sham controls (14.3±8.2% and 105.9±6.6%; p<0.05). Accordingly, the histomorphometric examination revealed an increased fraction of mineralized bone and osteoid (33.0±3.0% versus 28.5±3.6%; p<0.05). Of interest, this early effect of the initial 6-day EPO treatment was found vanished at 5 weeks after fracture healing. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.