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 #
2U01AG042143-14A1
Application #
8438124
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (05))
Program Officer
Joseph, Lyndon
Project Start
2013-08-01
Project End
2018-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
14
Fiscal Year
2013
Total Cost
$729,850
Indirect Cost
$229,178
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Yang, L; Parimi, N; Orwoll, E S et al. (2018) Association of incident hip fracture with the estimated femoral strength by finite element analysis of DXA scans in the Osteoporotic Fractures in Men (MrOS) study. Osteoporos Int 29:643-651
Janssen, Stefan; McDonald, Daniel; Gonzalez, Antonio et al. (2018) Phylogenetic Placement of Exact Amplicon Sequences Improves Associations with Clinical Information. mSystems 3:
Chalhoub, Didier; Boudreau, Robert; Greenspan, Susan et al. (2018) Associations Between Lean Mass, Muscle Strength and Power, and Skeletal Size, Density and Strength in Older Men. J Bone Miner Res 33:1612-1621
Rogers-Soeder, Tara S; Blackwell, Terri; Yaffe, Kristine et al. (2018) Rest-Activity Rhythms and Cognitive Decline in Older Men: The Osteoporotic Fractures in Men Sleep Study. J Am Geriatr Soc 66:2136-2143
Adabag, Selcuk; Vo, Tien N; Langsetmo, Lisa et al. (2018) Frailty as a Risk Factor for Cardiovascular Versus Noncardiovascular Mortality in Older Men: Results From the MrOS Sleep (Outcomes of Sleep Disorders in Older Men) Study. J Am Heart Assoc 7:
Langsetmo, L; Shikany, J M; Burghardt, A J et al. (2018) High dairy protein intake is associated with greater bone strength parameters at the distal radius and tibia in older men: a cross-sectional study. Osteoporos Int 29:69-77
Schwartz, Janice B; Gallagher, J Christopher; Jorde, Rolf et al. (2018) Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations. J Clin Endocrinol Metab 103:3278-3288
Feng, Lei; Langsetmo, Lisa; Yaffe, Kristine et al. (2018) No Effects of Black Tea on Cognitive Decline Among Older US Men: A Prospective Cohort Study. J Alzheimers Dis 65:99-105
Fink, Howard A; Langsetmo, Lisa; Vo, Tien N et al. (2018) Association of High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) bone microarchitectural parameters with previous clinical fracture in older men: The Osteoporotic Fractures in Men (MrOS) study. Bone 113:49-56
Jammy, Guru Rajesh; Boudreau, Robert M; Singh, Tushar et al. (2018) Volumetric bone mineral density (vBMD), bone structure, and structural geometry among rural South Indian, US Caucasian, and Afro-Caribbean older men. Arch Osteoporos 13:60

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