The Osteoporotic Fractures in Men (MrOS) study was formed primarily to quantify the determinants of fracture in men. Importantly, the MrOS cohort also provides a seminal opportunity to study men as they progress through a critical period of life in which problems of aging remain poorly understood. In 2000-2002, 5995 community-dwelling men ages 65 years and older (mean age: 72 years at baseline) were enrolled from 6 diverse US communities. After 5 years of follow-up, participant retention is excellent (99% of those alive remain active). We propose a new clinic visit and continued follow-up of the cohort to expand our understanding of risk factors for falls, fractures (particularly hip fracture) and other consequences of aging. At baseline, both areal (from DXA) and volumetric (from QCT) skeletal assessments were obtained. We propose to repeat the same assessments in the planned visit to identify the densitometric and biomechanical risk factors for hip fracture, as well as to characterize bone geometry changes that underlie skeletal fragility. Further, we will use the QCT scans to quantify femoral strength by finite element modeling (FEM), and assess the usefulness of FEM for fracture prediction. Additional follow-up of the cohort and repeat measures of muscle strength (grip strength, leg power), physical performance (gait speed, chair stands, and narrow walk), and self-reported physical activity will enable us to establish the extent and nature of change in activity and physical performance, identify biological predictors of these changes, and clarify the possibly joint effects of physical activity and physical performance on fracture risk. To objectively quantify physical activity we propose to obtain accelerometry measures at the new clinic visit. Using serum archived at baseline, we will test the hypothesis that renal function, vitamin D, parathyroid hormone have important effects on skeletal health, physical function and fracture risk, and will determine if lower sex steroid levels increase men's risk of skeletal deterioration and fracture, decline in physical function, and deterioration in quality of life. Combined with the considerable data and biologic specimens already collected, additional measures and extended follow-up in the MrOS cohort allows us to expand the understanding of hip fractures, the most devastating type of fracture in men, as well as address other health issues of compelling public health and clinical importance to older US men.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AR045614-13
Application #
8113276
Study Section
Special Emphasis Panel (ZAR1-EHB-H (M1))
Program Officer
Chen, Faye H
Project Start
1999-09-30
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
13
Fiscal Year
2011
Total Cost
$286,232
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Zheng, Hou-Feng; Forgetta, Vincenzo; Hsu, Yi-Hsiang et al. (2015) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526:112-7

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