Aims

There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV.

Aims

To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model.

Objectives. One commonly used rat fracture model for bone and mineral research is a closed mid-shaft femur fracture as described by Bonnarens in 1984. Initially, this model was believed to create very reproducible fractures. However, there have been frequent reports of comminution and varying rates of complication. Given the importance of precise anticipation of those characteristics in laboratory research, we aimed to precisely estimate the rate of comminution, its importance and its effect on the amount of soft callus created. Furthermore, we aimed to precisely report the rate of complications such as death and infection. Methods. We tested a rat model of femoral fracture on 84 rats based on Bonnarens’ original description. We used a proximal approach with trochanterotomy to insert the pin, a drop tower to create the fracture and a high-resolution fluoroscopic imager to detect the comminution. We weighed the soft callus on day seven and compared the soft callus parameters with the comminution status. Results. The mean operating time was 34.8 minutes (. sd. 9.8). The fracture was usable (transverse, mid-shaft, without significant comminution and with displacement < 1 mm) in 74 animals (88%). Of these 74 usable fractures, slight comminution was detected in 47 (63%). In 50 animals who underwent callus manipulation, slight comminution (n = 32) was statistically correlated to the amount of early callus created (r = 0.35, p = 0.015). Two complications occurred: one death and one deep infection. Conclusions. We propose an accurate description of comminution and complications in order to improve experiments on rat femur fracture model in the field of laboratory research. Cite this article: Bone Joint Res 2013;2:149–54

Objectives

Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing.

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.

We evaluated the effect of low-intensity pulsed ultrasound stimulation (LIPUS) on the remodelling of callus in a rabbit gap-healing model by bone morphometric analyses using three-dimensional quantitative micro-CT. A tibial osteotomy with a 2 mm gap was immobilised by rigid external fixation and LIPUS was applied using active translucent devices. A control group had sham inactive transducers applied. A region of interest of micro-CT was set at the centre of the osteotomy gap with a width of 1 mm. The morphometric parameters used for evaluation were the volume of mineralised callus (BV) and the volumetric bone mineral density of mineralised tissue (mBMD). The whole region of interest was measured and subdivided into three zones as follows: the periosteal callus zone (external), the medullary callus zone (endosteal) and the cortical gap zone (intercortical). The BV and mBMD were measured for each zone.

In the endosteal area, there was a significant increase in the density of newly formed callus which was subsequently diminished by bone resorption that overwhelmed bone formation in this area as the intramedullary canal was restored. In the intercortical area, LIPUS was considered to enhance bone formation throughout the period of observation. These findings indicate that LIPUS could shorten the time required for remodelling and enhance the mineralisation of callus.

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction.

After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm³ over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae.

The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis.