In-vivo forces and musculoskeletal loading conditions in human fracture healing

Project Introduction

The stabilization of bone parts during surgical fracture treatment plays a crucial role in the bone healing process. Research shows that applying small mechanical loads can enhance tissue regeneration, whereas excessive loading can disrupt it. In addition, factors such as patient anatomy, activity level, and fracture geometry directly influence the mechanical conditions at the fracture site. A well-controlled mechanical loading of the fracture site is therefore the main driver of the bone healing process. However, local interfragmentary kinematics remain unexplored in human patients, with no direct investigation or measurements performed so far.

Project Goals

We are aiming to assess the local interfragmentary motion occurring in human patients and differentiate between good and bad factors of influence by investigating the stresses and strains in fracture sites. These will allow us to confirm the validity of large animal studies and tissue deformations from in-silico models. Furthermore, we want to correlate various fracture shapes with the healing outcome by the means of statistical analysis of large number of fracture cases. This project will also lay the ground for validated recommendations on fracture fixation in humans (e.g., plate working length, plate position, screw positioning) and pave the way for personalised fracture treatment.

Strain Analysis in the Fracture Gap

It is known from animal experiments that a certain level of compression of the bone fracture site can enhance healing, while shear movement delays it. However, there is currently no data available to verify if the findings derived from large animals are also valid for humans. Furthermore, it is also largely unknown how the shape and positioning of a bone fixation plate (osteosynthesis) influence the local mechanical conditions at the fracture site. Only recently has gait analysis combined with in-silico musculoskeletal modelling allowed for the prediction of patient-specific interfragmentary loads. While such data exists for a small number of total joint replacement patients, in-vivo measurements of the interfragmentary motion have so far not been realized for a large group of human fracture patients.

In-silico experiments show that different screw placement and different fracture angles influence the stress distribution and stress type (compression vs. shear) within the fracture gap even when the same fixation plate is being used.

Measuring Interfragmentary Motion

To measure the patient-specific interfragmentary motion, a special bi-planar video fluoroscopy system was developed and set up at the OrthoLoad Lab (https://orthoload.com/ortholoadlab/), which is operated by our project partners from Charité University Medicine Berlin and Julius Wolff Institute. The bi-planar fluoroscopy system consists of two pairs of X-ray emitters and receivers that are positioned on movable robotic arms. It enables us to simultaneously monitor the fracture gap from two different perspectives in real-time under normal loading conditions while the patient is standing or walking on a treadmill.

Bi-planar video fluoroscopy setup with a radio-opaque bone phantom during initial imaging tests.

 
Initial imaging tests of a knee bones model demonstrate that the obtained X-ray images have high resolution and good quality but a limited field of view.

Since the bi-planar fluoroscopy only provides us with two 2D X-ray images, and since the interfragmentary motion is inherently a 3D problem, we employ a special 2D to 3D anatomy reconstruction algorithm (i.e., 2D-3D registration) that is capable of reconstructing a patient-specific fracture geometry given only one or two X-ray images. Similar methods have already been employed in the past in multiple studies and projects at ZIB. They demonstrated that 3D reconstruction of knee joint kinematics and implant position is possible and will now be extended to movements of tibia and femur bone fragments and fracture gaps under realistic loading conditions. For more information about 2D-3D registration please look at https://www.zib.de/projects/3d-reconstruction-anatomical-structures-2d-x-ray-images and https://www.zib.de/projects/dynamic-multi-modal-knee-joint-registration-analysis-knee-laxity.

Virtual bi-planar fluoroscopy setup for an in-silico example of 2D-3D registration of a femur bone. Registration solution (red) almost perfectly matches the known target solution (green).

Validation Study

Sub-millimeter precision of 2D-3D registration of bi-planar X-ray images is needed in order to evaluate small movements in the fracture gap. Thus, a validation study was caried out as a crucial step before experiments with real patients can begin. For the validation study, an artificial femur bone was cut in two pieces and stabilized with a real fixation plate in order to mimic the fracture gap. The bone was then fitted with optical markers and placed inside a custom-build compression testing machine, which is able to mimic real-world bone loading scenarios. As the bone was dynamically loaded during the X-ray imaging session, the positions of the optical markers were recorded with a PONTOS M5 optical system that has a reported average accuracy of 5.3 μm. 

Validation study. Artificial bone was fitted with a real fixation plate and with PONTOS optical markers. Obtained X-ray image of the bone during compressive loading can be seen on the right.