Genetic epidemiology of longitudinal change in bone mineral density

De Dios, Krisel L.

Genetic epidemiology of longitudinal change in bone mineral density

De Dios, Krisel L.

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Publication Type:: Thesis
Issue Date:: 2025

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Field	Value	Language
dc.contributor.author	De Dios, Krisel L.
dc.date.accessioned	2026-07-27T01:57:48Z
dc.date.available	2026-07-27T01:57:48Z
dc.date.issued	2025
dc.identifier.uri	http://hdl.handle.net/10453/195806
dc.description	University of Technology Sydney. Faculty of Engineering and Information Technology.	en_US.UTF-8
dc.description.abstract	Osteoporosis is characterised by low bone mineral density (BMD), microarchitectural deterioration of bone tissue, and an increased risk of fracture. These hallmark features arise from disrupted bone homeostasis, where bone resorption occurs at a higher rate than bone formation, leading to progressive skeletal decline. This thesis aimed to investigate the relationship between bone loss and fracture risk and to identify both overlapping and distinct genetic variants associated with longitudinal bone change. By moving beyond static BMD measures, this work provides novel insights into bone loss trajectories and their implications for fracture prediction and clinical management. This thesis is based on several large, prospective longitudinal cohort studies, including the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men Study (MrOS), the Dubbo Osteoporosis Epidemiology Study (DOES), and the Vietnam Osteoporosis Study (VOS). The findings demonstrate that bone loss is an independent risk factor for hip fracture in men, even after adjusting for pre-defined covariates. Furthermore, genetic analyses identified associations between specific FTO single nucleotide polymorphisms (SNPs) and hip fracture risk, with minor homozygous alleles emerging as potential clinical biomarkers of increased susceptibility. In addition, novel loci linked to longitudinal bone change were discovered, underscoring the value of capturing dynamic skeletal processes rather than relying solely on cross-sectional BMD measures. In conclusion, this thesis highlights bone loss as a central element contributing to low BMD, microarchitectural deterioration, and fracture risk. It also establishes that overlapping and distinct genetic determinants underlie longitudinal bone change, pointing to new skeletal pathways for further investigation. Collectively, these findings advance the understanding of osteoporosis pathophysiology and provide a framework for incorporating bone loss trajectories into future diagnostic, predictive, and therapeutic approaches.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/195806/1/thesis.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2025 Krisel L. De Dios
dc.rights	au.edu.uts.lib/cph
dc.title	Genetic epidemiology of longitudinal change in bone mineral density	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Osteoporosis is characterised by low bone mineral density (BMD), microarchitectural deterioration of bone tissue, and an increased risk of fracture. These hallmark features arise from disrupted bone homeostasis, where bone resorption occurs at a higher rate than bone formation, leading to progressive skeletal decline. This thesis aimed to investigate the relationship between bone loss and fracture risk and to identify both overlapping and distinct genetic variants associated with longitudinal bone change. By moving beyond static BMD measures, this work provides novel insights into bone loss trajectories and their implications for fracture prediction and clinical management. This thesis is based on several large, prospective longitudinal cohort studies, including the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men Study (MrOS), the Dubbo Osteoporosis Epidemiology Study (DOES), and the Vietnam Osteoporosis Study (VOS). The findings demonstrate that bone loss is an independent risk factor for hip fracture in men, even after adjusting for pre-defined covariates. Furthermore, genetic analyses identified associations between specific FTO single nucleotide polymorphisms (SNPs) and hip fracture risk, with minor homozygous alleles emerging as potential clinical biomarkers of increased susceptibility. In addition, novel loci linked to longitudinal bone change were discovered, underscoring the value of capturing dynamic skeletal processes rather than relying solely on cross-sectional BMD measures. In conclusion, this thesis highlights bone loss as a central element contributing to low BMD, microarchitectural deterioration, and fracture risk. It also establishes that overlapping and distinct genetic determinants underlie longitudinal bone change, pointing to new skeletal pathways for further investigation. Collectively, these findings advance the understanding of osteoporosis pathophysiology and provide a framework for incorporating bone loss trajectories into future diagnostic, predictive, and therapeutic approaches.

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http://hdl.handle.net/10453/195806