Date of Award

2024

Degree Name

Doctor of Philosophy (School of Physiotherapy)

Schools and Centres

Physiotherapy

First Supervisor

Associate Professor Dale Edgar

Second Supervisor

W. Professor Fiona Wood; Dr Ed Raby

Third Supervisor

Associate Professor Mark Fear

Fourth Supervisor

Associate Professor Nathan Pavlos

Abstract

Traumatic heterotopic ossification (tHO) refers to the complication of pathological formation of ectopic bone in soft tissues, which follows tissue insult secondary to burn, neurological and orthopaedic injury [2]. Common to these diagnoses is the involvement of central and or peripheral nervous system trauma. Although known risk factors are associated with developing tHO, the underlying cellular and molecular mechanisms are not fully understood. Research to date, primarily in single injury cohorts, has provided minimal translatable results [2]. Thus, clinical guidelines for early screening and prophylactic drug therapy are lacking, and treatment options are limited. To move the body of knowledge forward, machine learning approaches, such as IBM Watson for Drug Discovery (WDD), may offer a solution to enhance basic science discovery by providing important insights into the biological processes and genetic influences implicated in tHO. Investigating the key genes and signalling pathways that are dysregulated in and related to the development of tHO through analysis of human biospecimens may lead to the identification of putative targets that could be used to elucidate the underlying mechanisms of pathological ectopic bone formation. Fibroblasts, which can acquire bone-forming characteristics under dysregulated neuroinflammatory conditions induced by injury, make them an attractive candidate progenitor cell that may contribute to tHO pathogenesis.

The challenges to enhancing clinical tHO management are highlighted in the burn patient context, as despite four decades of research, the lack of translatable evidence is stark, and difficulties in conducting multi-centre trials due to low event rate and patient care heterogeneity remain [2]. Thus, injury complicated by tHO significantly impacts patient quality of life, hampering physical and psychosocial functioning and impeding rehabilitation [3]. As such, it is hypothesised that a diagnosis of tHO in trauma patients prolongs hospital length of stay (LOS) and increases healthcare costs.

Furthermore, at the commencement of this program of research, there were no published epidemiological data available for Western Australian (WA) tertiary hospital trauma patients to help iv understand tHO prevalence, LOS outcomes and risk profile or data evaluating the accuracy of medical diagnostic coding and specificity of clinical documentation for tHO diagnoses. Purposeful multi-centre data pooling of at-risk trauma populations was therefore warranted and instigated as part of this research program to address several aforementioned research, understanding and clinical practice gaps. Specifically, to comprehensively explore and identify novel tHO risk factors and to quantify the impact of tHO on the health care system. By combining information from burn patients and individuals with a higher prevalence of tHO, this program aimed to unveil underlying causes that may not be apparent due to the relative rarity of tHO following burns in the WA cohort. This research program aimed to explore and seek a novel understanding of the pathophysiology, epidemiology, clinical characteristics, and risk factors of traumatic heterotopic ossification in adult trauma patients. To confirm novel and applicable results, the methods were designed to build a detailed risk profile and define the mechanisms that perpetuate the tHO process to provide new targets for detection, prevention, and intervention.

Download Complete Thesis
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Included in

Physiotherapy Commons

Share

COinS