UC Irvine

Musculoskeletal disorders are a major source of disability, reduced quality of life, and healthcare burden across the lifespan. Although osteoporosis in older adults and musculoskeletal injuries in younger populations is often studied separately, both may reflect broader vulnerabilities in musculoskeletal health shaped by systemic conditions and population-level disparities. This dissertation examined musculoskeletal health across the life course using large-scale real-world data, with a particular focus on metabolic disease, neurocognitive disorders, and population patterns of injury treatment.This dissertation employed a multi-study epidemiologic approach using three large healthcare data sources: the National Institutes of Health All of Us Research Program, national Medicare claims data, and the TriNetX research network. Chapter 1 evaluated the association between diabetes mellitus and osteoporosis in a diverse U.S. cohort from the All of Us Research Program. Chapter 2 investigated the bidirectional longitudinal relationship between osteoporosis and Alzheimer’s disease and related dementias (ADRD) among older adults using Medicare data. Chapter 3 examined national trends and demographic disparities in anterior cruciate ligament (ACL) injury and reconstruction using the TriNetX network. In Chapter 1, type 1 diabetes mellitus (T1DM) was strongly associated with higher odds of osteoporosis, whereas type 2 diabetes mellitus (T2DM) showed a more modest association, with the strongest associations observed among non-Hispanic Black participants. Chapter 2 reversed the direction of inquiry to ask whether skeletal health itself marks broader aging-related vulnerability. I found baseline osteoporosis was associated with a modestly higher risk of incident ADRD. In the reverse direction, however, baseline ADRD was associated with lower observed osteoporosis incidence after adjusting for demographics, comorbidities, rurality, and baseline healthcare utilization, a pattern that might be more likely to be caused by disparities in timely diagnosis and competing mortality than a protective effect of ADRD on osteoporosis risk. Both chapters rely on conditions recorded during routine care, raising the question of how access to that care itself is distributed. Chapter 3 investigate that question in a younger population with a different outcome: ACL reconstruction rates declined during the COVID-19 pandemic in 2020 and subsequently returned to pre-pandemic levels, but the reconstruction rate among non-Hispanic Black patients was consistently lower than that in other racial and ethnic groups. Disparities affecting this group therefore emerged in both the disease burden of Chapter 1 and the treatment access of Chapter 3, at different points along the pathway from biology to care. Taken together, these findings demonstrate that musculoskeletal health is shaped by both systemic health conditions and sociodemographic inequities, with different clinical manifestations across the life course. In older adults, these processes are reflected in skeletal fragility and its association with chronic disease and neurodegeneration, while in younger populations they appear in patterns of musculoskeletal injury and treatment disparities. This dissertation provides a broader population health perspective on musculoskeletal vulnerability and underscores the importance of integrating systemic disease burden, aging, and healthcare equity into future musculoskeletal research and prevention strategies.