The availability of a broad spectrum of antibodies and gene-targeted animals caused an increasing interest in mouse models for the study of molecular mechanisms of fracture healing and bone regeneration. In most murine fracture models, the tibia or the femur is fractured using a 3-point bending device (closed models) or is osteotomized using an open surgical approach (open models). For fracture studies in mice, the tibia has to be considered less appropriate compared with the femur because the stabilization of the fracture is more difficult due to its triangular, distally declining caliber and its bowed longitudinal axis. Biomechanical factors critically influence the bone healing process. Thus, the use of stable osteosynthesis techniques is also of interest in murine fracture models. To achieve stable fixation, several biomechanically standardized implants have recently been introduced, including a locking nail and an intramedullary compression screw. Other implants, such as a pin-clip, an external fixator, and a locking plate, additionally allow the stabilization of fractures with distinct gap sizes. This enables the study of healing of critical size defects and nonunions. The use of these implants further allows a rigid fixation of fractures in bridle bones, which is essential for fracture studies in animals suffering from metabolic bone diseases like osteoporosis. In general, the analysis of bone healing in these models includes different imaging techniques and histologic, immunohistochemical, biomechanical, and molecular methods. To evaluate the impact of different osteosynthesis techniques on physical activity and rehabilitation, gait analysis may additionally be performed. By this, the gait of the animals can be visualized and quantitatively analyzed using modified running wheels and dynamic high-resolution radiography systems. Taken together, a variety of different murine femur fracture models have become available, providing defined biomechanical conditions for fracture research. The use of these mouse models may now allow studying the influence of fracture stabilization techniques on molecular mechanisms of bone healing.

The various molecular mechanisms of cell regeneration and tissue healing can best be studied in mouse models with the availability of a wide range of monoclonal antibodies and gene‐targeted animals. The influence of the mechanical stability of individual stabilization techniques on the molecular mechanisms of fracture healing has not been completely elucidated yet. Although during recent years several osteosynthesis techniques have been introduced in mouse fracture models, no comparative study on fracture stabilization is available yet. We therefore analyzed herein in a standardized ex vivo setup the rotational stiffness of seven different osteosynthesis techniques using osteotomized right cadaver femora of CD‐1 mice. Uninjured femora without osteotomy served as controls. Femur stabilization with a locking plate or an external fixator resulted in a rotational stiffness almost similar to the intact femur. The use of a “pin‐clip” device, a “locking nail,” a “mouse nail,” or an “intramedullary screw” produced a lower torsional stiffness, which, however, was still significantly higher than that achieved with the widely applied conventional pin. By the use of the presented data a more specific choice of stabilization technique will be possible according to the various questions concerning molecular aspects in fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1152–1156, 2009

In most murine fracture models, the femur is stabilized by an intramedullary implant and heals predominantly through endochondral ossification. The aim of the present study was to establish a mouse model in which fractures heal intramembranously. Femur fractures of 16 SKH-mice were stabilized by an internal locking plate. Femur fractures of another 16 animals were stabilized by an intramedullary screw. Bone repair was analyzed by radiographic, biomechanical, and histological methods. At 2 weeks, histological analysis showed a significantly smaller callus diameter and callus area after locking plate fixation. Cartilage formation within the callus could only be observed after screw fixation, but not after fracture stabilization with the locking plate. Radiological and biomechanical analysis after 2 and 5 weeks showed a significantly improved healing and a higher bending stiffness of fractures stabilized by the locking plate. Fractures stabilized by the locking plate healed exclusively by intramembranous ossification, which is most probably a result of the anatomical reduction and stable fixation. The fractures that healed by intramembranous ossification showed an increased stiffness compared to fractures that healed by endochondral ossification. This model may be used to study molecular mechanisms of intramembranous bone healing. ß