A new model to analyze metaphyseal bone healing in mice

Abstract

BackgroundDespite the increasing clinical problems with metaphyseal fractures, most experimental studies investigate the healing of diaphyseal fractures. Although the mouse would be the preferable species to study the molecular and genetic aspects of metaphyseal fracture healing, a murine model does not exist yet. Using a special locking plate system, we herein introduce a new model, which allows the analysis of metaphyseal bone healing in mice. MethodsIn 24 CD-1 mice the distal metaphysis of the femur was osteotomized. After stabilization with the locking plate, bone repair was analyzed radiologically, biomechanically, and histologically after 2 (n=12) and 5wk (n=12). Additionally, the stiffness of the bone-implant construct was tested biomechanically ex vivo. ResultsThe torsional stiffness of the bone-implant construct was low compared with nonfractured control femora (0.23±0.1Nmm/° versus 1.78±0.15Nmm/°, P<0.05). The cause of failure was a pullout of the distal screw. At 2wk after stabilization, radiological analysis showed that most bones were partly bridged. At 5wk, all bones showed radiological union. Accordingly, biomechanical analyses revealed a significantly higher torsional stiffness after 5wk compared with that after 2wk. Successful healing was indicated by a torsional stiffness of 90% of the contralateral control femora. Histological analyses showed new woven bone bridging the osteotomy without external callus formation and in absence of any cartilaginous tissue, indicating intramembranous healing. ConclusionWith the model introduced herein we report, for the first time, successful metaphyseal bone repair in mice. The model may be used to obtain deeper insights into the molecular mechanisms of metaphyseal fracture healing.