Comparison of healing process in open osteotomy model and open fracture model: Delayed healing of osteotomies after intramedullary screw fixation.
Murine osteotomy and fracture models have become the standard to study molecular mechanisms of bone healing. Because there is little information whether the healing of osteotomies differs from that of fractures, we herein studied in mice the healing of femur osteotomies compared to femur fractures. Twenty CD-1 mice underwent a standardized open femur osteotomy. Another 20 mice received a standardized open femur fracture. Stabilization was performed by an intramedullary screw. Bone healing was studied by micro-CT, biomechanical, histomorphometric and protein expression analyses. Osteotomies revealed a significantly lower biomechanical stiffness compared to fractures. Micro-CT showed a reduced bone/tissue volume within the callus of the osteotomies. Histomorphometric analyses demonstrated also a significantly lower amount of osseous tissue in the callus of osteotomies (26% and 88% after 2 and 5 weeks) compared to fractures (50% and 100%). This was associated with a delayed remodeling. Western blot analyses demonstrated comparable BMP-2 and BMP-4 expression, but higher levels of collagen-2, CYR61 and VEGF after osteotomy. Therefore, we conclude that open femur osteotomies in mice show a markedly delayed healing when stabilized less rigidly with an intramedullary screw. This should be considered when choosing a model for studying the mechanisms of bone healing in mice.
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421, Homburg/Saar, Germany.
Moritz
M
Klein
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421, Homburg/Saar, Germany.
Andrea
A
Stieger
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421, Homburg/Saar, Germany.
David
D
Stenger
Institute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, Germany.
Claudia
C
Scheuer
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421, Homburg/Saar, Germany.
Jörg H
JH
Holstein
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421, Homburg/Saar, Germany.
Tim
T
Pohlemann
Institute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, Germany.
Michael D
MD
Menger
Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421, Homburg/Saar, Germany.
Tina
T
Histing
D000818:Animals; D015153:Blotting, Western; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology; D005269:Femur / Q000473:pathology; D005594:Fracture Fixation, Intramedullary; D017102:Fracture Healing; D005597:Fractures, Open / Q000000981:diagnostic imaging / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D010027:Osteotomy; D055114:X-Ray Microtomography
CYR61; VEGF; bone healing; callus remodeling; mouse