Examining changes in bone geometry and bone strength

Can changes in bone geometry and bone strength be linked to fracture risk in Paget’s disease ? This was the research question asked by Alisha Sharma from the University of Southampton when she received the Sir Julian Paget Student Research Bursary from Patron, Sir Henry Paget. [2019-2020] 

Assessment of sexually dimorphic bone shape and vascular alterations as indicators of Paget’s disease

Alisha describes her research project below.

Firstly, I personally would like to take this opportunity to thank the Paget’s Association for awarding me the Sir Julián Paget Student Research Bursary. Currently, I hold a degree in biochemistry and am working towards my PhD in bioengineering at the University of Southampton. My research primarily focuses on Paget’s Disease of Bone, specifically looking at bone shape and strength.

My research aims to answer the question, ‘Can changes in bone geometry and bone strength be linked to fracture risk in Paget’s Disease of Bone?’. Before I could answer this question, a model to study Paget’s disease was required. I used the SQSTM1 gene, a gene many scientists believe to play a key role in the cause of this disease. My collaborator, Professor Stuart Ralston has made artificial changes in the DNA of this gene to use for a model of Paget’s disease. Using this model, I aim to examine bone shape changes and identify whether this links to the strength of bone and ultimately whether this affects fracture occurrence in Paget’s disease. Fracture is a predominant impediment, yet treatment and prevention remain a significant challenge. Simple new methods are urgently required for early diagnosis to prevent bone fractures in Paget’s disease, which are not only debilitating but are linked to increased morbidity. With poor bone quality accounting for several complications of this condition, I aim to identify whether bone shape can be used as an early predictor of Paget’s disease and fracture occurrence.

I will use technology called micro-computed tomography to assess bone structure in both males and females. This involves high energy x-rays, which are used to scan the bones. Using these scans, I can evaluate the shape of the bones without damaging them. As bone shape (such as size) impacts the mechanical competence (strength) of bone, I will do a series of strength tests to determine how geometrical changes in bone affected by Paget’s disease could link to strength and ultimately fracture. Specifically, I have developed a model to assess strength. This model works by applying force to the bone and measuring the amount of force required to break the bone. Further assessment on where the break occurs can then be conducted. Together, these experiments will help assess whether changes in bone geometry can be used to predict fracture risk and location. In addition, with increased blood flow levels reported in case of Paget’s disease, I will also use more powerful micro-computed tomography to visualise some of the internal structures (blood vessels) inside the bone.

Currently, my studies have shown that bone shape and strength can vary depending on gender. Thus, my long-term future research goal is to discover whether development of future treatments should be targeted to gender.

Alisha