- Research from the Healthy Lifespan Institute has discovered high levels of sensitivity when using external force in the in vivo tibial loading model to treat osteoporosis in mice
- The new study in Frontiers in Bioengineering and Biotechnology generates opportunities to minimise error of the loading direction when using the in vivo tibial loading model, through the development of subject-specific loading caps
Research by PhD student Saira Farage-O'Reilly highlights how the direction of applying external force to the bone dramatically affects the strength of mouse tibia.
Bone is a dynamic tissue that changes over time due to biomechanical and biochemical stimuli. Osteoporosis is a health condition that weakens bones over time and makes them more fragile and likely to break.
Previous preclinical studies have examined the use of external methods, such as the use of the in vivo tibial loading model,to evaluate the effect of external loading on bone adaptation in mice. This non-invasive method involves placing the tibia within two loading caps to apply force to the bone and stimulate bone remodelling.
However, every time the leg is positioned in the device, it can be slightly misaligned which impacts the repositioning of the bone. As the device is used in vivo, the force is applied through the knee and ankle joints which creates uncertainty in the direction of the force onto the bone itself.
A preclinical study from the Healthy Lifespan Institute at the University of Sheffield used a computer model to test the effect of applying the force in over 500 different directions on the mechanical properties of the bone, including bone strength and stiffness.
The study was led by PhD student Saira Farage-O'Reilly from the Healthy Lifespan and Insigneo Institutes at the University of Sheffield. The study was partially funded by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research, and by the Engineering and Physical Sciences Research Council (EPSRC) Frontier Multisim Grant and by the University of Sheffield’s EPSRC Doctoral Training Partnership.
The findings, published in Frontiers in Bioengineering and Biotechnology, show that bone strength is affected by the loading direction, with changes ranging from half to double depending on the direction of the force.
“The findings highlight the sensitivity of the loading direction when using the in vivo tibial loading model, which dramatically affects the bone strength. The study shows the importance of being aware of the consequences of applying the load in a certain direction, as in some directions the bone strength is stronger. As well as being important for animal welfare through heightened risk of fracture of the leg of the mouse, this study provides more understanding to develop advanced multiscale computational models of bone remodelling which include both biomechanical and biochemical stimuli” says Saira Farage-O'Reilly.