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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
4U01AG042168-17
Application #
9041474
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Joseph, Lyndon
Project Start
2013-08-01
Project End
2018-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
17
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Family Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Cawthon, Peggy M; Patel, Sheena; Ewing, Susan K et al. (2017) Bone Loss at the Hip and Subsequent Mortality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study. JBMR Plus 1:31-35
Rogers, Tara S; Blackwell, Terri L; Lane, Nancy E et al. (2017) Rest-activity patterns and falls and fractures in older men. Osteoporos Int 28:1313-1322
Kaplan, Katherine A; Hirshman, Jason; Hernandez, Beatriz et al. (2017) When a gold standard isn't so golden: Lack of prediction of subjective sleep quality from sleep polysomnography. Biol Psychol 123:37-46
Winkelman, John W; Blackwell, Terri; Stone, Katie et al. (2017) Associations of Incident Cardiovascular Events With Restless Legs Syndrome and Periodic Leg Movements of Sleep in Older Men, for the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep Study). Sleep 40:
Schousboe, John T; Vo, Tien N; Langsetmo, Lisa et al. (2017) Association of Trabecular Bone Score (TBS) With Incident Clinical and Radiographic Vertebral Fractures Adjusted for Lumbar Spine BMD in Older Men: A Prospective Cohort Study. J Bone Miner Res 32:1554-1558
Fink, H A; Litwack-Harrison, S; Taylor, B C et al. (2017) Erratum to: Clinical utility of routine laboratory testing to identify possible secondary causes in older men with osteoporosis: the osteoporotic fractures in men (MrOS) study. Osteoporos Int 28:419-420
Langsetmo, Lisa; Shikany, James M; Cawthon, Peggy M et al. (2017) The Association Between Protein Intake by Source and Osteoporotic Fracture in Older Men: A Prospective Cohort Study. J Bone Miner Res 32:592-600
Schousboe, John T; Langsetmo, Lisa; Schwartz, Ann V et al. (2017) Comparison of Associations of DXA and CT Visceral Adipose Tissue Measures With Insulin Resistance, Lipid Levels, and Inflammatory Markers. J Clin Densitom 20:256-264
Sheu, Yahtyng; Amati, Francesca; Schwartz, Ann V et al. (2017) Vertebral bone marrow fat, bone mineral density and diabetes: The Osteoporotic Fractures in Men (MrOS) study. Bone 97:299-305
Bozorgmehri, Shahab; Fink, Howard A; Parimi, Neeta et al. (2017) Association of Sleep Disordered Breathing with Erectile Dysfunction in Community Dwelling Older Men. J Urol 197:776-782

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