DESCRIPTION (provided by applicant): Age-related deterioration in bone, muscle and physical performance, manifested as osteoporosis, sarcopenia, and disability, are major causes of morbidity and mortality in the elderly. It is a priority to understand how musculoskeletal phenotypes and physical activity change with age, the factors that contribute to these changes, and how changes impact clinically important health outcomes. MrOS is a unique prospective study of 5994 older men that has been extremely productive in expanding our understanding of age-related change in musculoskeletal health. Initiated in 2000, it includes extensive longitudinal, objective, state-of-the-art assessments of bone, muscle, physical performance, physical activity and health outcomes, as well as biospecimen and imaging archives. We propose to extend these resources to allow a comprehensive and integrated understanding of the processes and consequences of musculoskeletal aging and decline in physical activity in older men studied over a 15 year period. The overall long term goal of the project is to identity men at risk of adverse health outcomes who may benefit from preventive measures and rehabilitation, discover new targets for treating and preventing declines in musculoskeletal health and activity, and improve our understanding of optimal aging (men who maintain their musculoskeletal health and activity levels over an average overall follow-up of 15 years). Specifically, we will leverage our repeated measurements to define age- related trajectories in phenotypes of musculoskeletal health, physical performance, and physical activity in order to determine factors that predict and contribute to these trajectories. We will test the hypotheses that favorable trajectories in musculoskeletal health are associated with lower risks of incident falls, fractures, disability and mortality and that age-related deterioration in bone, muscle and physical performance can occur concurrently; combined deterioration magnifies the risk of poor functional and health outcomes. Second, we will characterize change and trajectories in activity levels in older men using our repeated state-of-the-art questionnaire and objectively assessed energy expenditure from accelerometry. Third, we will take advantage of a linkage of MrOS with Medicare Claims data to determine the association of trajectories in musculoskeletal phenotypes and activity with inpatient and nursing home related health care utilization. Fourth, we will examine novel characteristics of cortical bone that may cause age-related skeletal fragility by using high resolution peripheral quantitative computed tomography to measure cortical porosity. We will relate trajectories of musculoskeletal health and activity to these measures of cortical bone and test whether increased cortical porosity is related to fractures. Finally, we will continue to leverage MrOS as a platform for new science and the training of investigators. Our application is consistent with the mission of the NIA and NIAMS to conduct research related to the aging process and diseases and conditions associated with musculoskeletal aging, and foster the development of new research scientists in this scientific area.

PUBLIC HEALTH RELEVANCE: Decreases in bone, muscle, physical performance and physical activity occur with advancing age and can lead to increased risk of fractures, falls, disability and death. These declines may also lead to substantial and potentially preventable increases in health care utilization, further straining our limited health care resources. During this next phase of MrOS, the largest cohort designed to study musculoskeletal aging, we will expand our current understanding of musculoskeletal aging, the trajectories of change in musculoskeletal function, factors that may contribute to change or the maintenance of health, and the relationship of these trajectories to important health outcomes.