Advances in the establishment of defined mouse models for the study of fracture healing and bone regeneration.

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.