Genetic and Environmental Determinants of Bone Phenotypes

Huynh, Ngoc Bao

Genetic and Environmental Determinants of Bone Phenotypes

Huynh, Ngoc Bao

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Publication Type:: Thesis
Issue Date:: 2025

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Field	Value	Language
dc.contributor.author	Huynh, Ngoc Bao
dc.date.accessioned	2025-09-10T03:38:10Z
dc.date.available	2025-09-10T03:38:10Z
dc.date.issued	2025
dc.identifier.uri	http://hdl.handle.net/10453/189757
dc.description	University of Technology Sydney. Faculty of Engineering and Information Technology.	en_US.UTF-8
dc.description.abstract	Osteoporosis is a metabolic disease characterized by reduced bone strength and deteriorating bone structure, leading to an increased risk of fragility fractures, which in turn, signal an increased risk of refracture and mortality. The lifetime fracture risk of fracture is approximately 1 in 2 for women and 1 in 3 for men, with around 9 million osteoporosis related fractures occurring globally each year, making osteoporosis a serious public health concern. Bone mineral density (BMD) is the most robust risk factor for fractures, yet BMD loss in the elderly varies widely among individuals. Although twin studies indicate that genetic factors influence this variation, the extent of their impact remains poorly understood. This study aimed to investigate the contributions of specific genetic variants and lifestyle factors to BMD, bone loss, and fracture risk, to improve early detection, prevention, and treatment strategies for osteoporosis. The present study was based on data from four major cohorts: the Dubbo Osteoporosis Epidemiology Study (DOES), the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men Study (MrOS), and the Vietnam Osteoporosis Study (VOS). The cohorts included over 10,000 participants aged 60 years and older with repeated BMD measurements. Study 1 tested the hypothesis that increased bone loss is a risk factor for mortality, finding that rapid declines in femoral neck BMD significantly increased mortality risk, while stable or slightly improved BMD reduced it, highlighting BMD maintenance as a marker for healthy aging. Study 2 examined lifestyle factors, showing that smoking accelerated bone loss, while alcohol consumption, regular physical activity, and adequate dietary calcium intake reduced it. Study 3 examined the association between bone loss and COLIA1 gene polymorphisms, finding the Sp1 TT genotype doubled fracture risk but was not linked to bone loss, suggesting a role in bone fragility independent of bone loss. Study 4 was a genome-wide association analysis that identified 16 genetic variants associated with BMD in individuals of Southeast Asian descent, including novel variants in genes such as SORCS2, LINC02131, and ATXN10, accounting for 0.6% to 1.3% of BMD heritability. Collectively, these studies underscore the multifactorial nature of bone loss and fracture risk, suggesting that combining genetic data with clinical and lifestyle factors could enhance fracture risk prediction and support personalized osteoporosis management strategies.	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/10453/189757/1/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 Ngoc Bao Huynh
dc.rights	au.edu.uts.lib/cph
dc.title	Genetic and Environmental Determinants of Bone Phenotypes	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Osteoporosis is a metabolic disease characterized by reduced bone strength and deteriorating bone structure, leading to an increased risk of fragility fractures, which in turn, signal an increased risk of refracture and mortality. The lifetime fracture risk of fracture is approximately 1 in 2 for women and 1 in 3 for men, with around 9 million osteoporosis related fractures occurring globally each year, making osteoporosis a serious public health concern. Bone mineral density (BMD) is the most robust risk factor for fractures, yet BMD loss in the elderly varies widely among individuals. Although twin studies indicate that genetic factors influence this variation, the extent of their impact remains poorly understood. This study aimed to investigate the contributions of specific genetic variants and lifestyle factors to BMD, bone loss, and fracture risk, to improve early detection, prevention, and treatment strategies for osteoporosis. The present study was based on data from four major cohorts: the Dubbo Osteoporosis Epidemiology Study (DOES), the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men Study (MrOS), and the Vietnam Osteoporosis Study (VOS). The cohorts included over 10,000 participants aged 60 years and older with repeated BMD measurements. Study 1 tested the hypothesis that increased bone loss is a risk factor for mortality, finding that rapid declines in femoral neck BMD significantly increased mortality risk, while stable or slightly improved BMD reduced it, highlighting BMD maintenance as a marker for healthy aging. Study 2 examined lifestyle factors, showing that smoking accelerated bone loss, while alcohol consumption, regular physical activity, and adequate dietary calcium intake reduced it. Study 3 examined the association between bone loss and COLIA1 gene polymorphisms, finding the Sp1 TT genotype doubled fracture risk but was not linked to bone loss, suggesting a role in bone fragility independent of bone loss. Study 4 was a genome-wide association analysis that identified 16 genetic variants associated with BMD in individuals of Southeast Asian descent, including novel variants in genes such as SORCS2, LINC02131, and ATXN10, accounting for 0.6% to 1.3% of BMD heritability. Collectively, these studies underscore the multifactorial nature of bone loss and fracture risk, suggesting that combining genetic data with clinical and lifestyle factors could enhance fracture risk prediction and support personalized osteoporosis management strategies.

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