National Institutes of Health (NIH) RO1

Grant Number: 1R01AG029571-01A2

Project Title: The Proximal Femoral Musculature: A new Risk Factor for Hip Fracture

Principal Investigator: Thomas F. Lang

Description:

Osteoporotic fracture has a complex etiology involving skeletal fragility, risk of falling, and impaired reaction to a fall once it is initiated. Currently, quantitative bone assessments such as dual x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) act as surrogates for skeletal strength but are of limited value as surrogates of fracture risk because they do not provide information on non-skeletal risk factors such as falls. Studies have shown that fall risk is associated with reduced muscle strength, particularly of the proximal femoral musculature. The QCT image of the hip provides information on the size and composition of the proximal femoral muscles, and studies at various skeletal sites have shown correlations between muscle strength and muscle size and attenuation measured by x-ray CT. In our laboratory, we have recently shown that combination of muscle size and attenuation data with the CT skeletal measures markedly improves the discriminatory power of the CT measurement. Here, we propose to develop computer algorithms to assess muscle size and attenuation from QCT hip images, prospectively validate that these measures improve fracture prediction when used in combination with hip QCT bone variables, and determine the mechanism by which they predict fracture. (Complete description)

National Institutes of Health (NIH) RO1

Grant Number: 1R01AG028832-01A1

Project Title: Age-related changes in proximal femoral strength in men and women

Principal Investigator: Thomas F. Lang

Description:

The exponential increase in hip fracture incidence with age cannot be explained either by the age-related decrease in area! bone mineral density (aBMD) or by the increase of fall risk with age. Recent studies have outlined age-related changes in hip structure that appear to result in increased fragility but that may not be reflected in bone density measurements. ... In this study, we expect to derive clinically relevant information regarding the effect regarding how the structural characteristics of the proximal femur and its strength change with age and how they contribute to fracture risk. (Complete description)

 

National Space Biomedical Research Institute (NSBRI)

Project Title: An Integrated Musculoskeletal Countermeasure Battery for Long-Duration Lunar Missions

Principal Investigator: Thomas F. Lang

Description:

It is unknown how well the musculoskeletal system will hold up during long stays in the reduced gravity of the lunar surface. It's likely that without countermeasures, there will be adaptive changes in muscle strength, bone mineral density, bone geometry and sensorimotor ability....Using pre-and post-bedrest comparisons of aerobic capacity, balance, muscle strength, biochemical and imaging-based measures of skeletal metabolism, density and strength, the team will determine whether the countermeasure preserves fall and injury-related indices of neuromuscular performance while maintaining skeletal integrity and cardiovascular function. (Complete description) (Technical Summary)

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National Space Biomedical Research Institute (NSBRI)

Project Title: Musculoskeletal Alterations Team Leader

Principal Investigator: Thomas F. Lang

Description:

In May 2008, Thomas Lang was chosen as leader of the Musculoskeletal Alterations Team of the National Space Biomedical Research Institute. The NSBRI is a non-profit institute which carries out research in the effects of spaceflight on human physiology and behavior. The research program of the NSBRI is broken up into multiple disciplines, including musculoskeletal studies, cardiovascular studies, behavioral science and neuroscience. (Complete description)

National Institutes of Health (NIH) RO1
Grant Number: 1R01AR054496-01A2
Project Title: A Study of Reduced Bone Quality as a cause of Fractures
Principal Investigator: Robert Recker

Description:

Bone quality factors other than bone density determine more than half of the propensity to fracture in patients suffering osteoporosis. A number of candidate bone quality defects have been described, but their relative importance in patients who are suffering fractures has not yet been explored. The purpose of this study is to characterize these defects in bone quality that contribute to low trauma fractures in postmenopausal women. The general hypothesis is: In postmenopausal women with osteopenia, measured values of bone quality factors differentiate those who sustain low-trauma fractures from those who do not. ... The secondary hypothesis is: Postmenopausal women with low-trauma fractures have reduced bone quality as indicated by a battery of clinical measures compared to those that have not fractured. ... This project will point the direction for research into the cause of fractures and the development of diagnostic methods to predict risk of fractures before they occur, and into development of surrogate measures for fracture that could be used in human treatment trials. (Complete description)

 

National Institutes of Health (NIH) RO1

Grant Number: 2R01AR041398-16A1

Project Title: Risk Factors for Aged Related Bone Loss

Principal Investigator: Douglas Kiel

Description:

The long-term objective of this project is to better define risk factors for age-related bone loss and fractures. For the past 15 years, this research program has focused on three specific themes; 1) fracture epidemiology by establishing the Framingham Fracture Registry, 2) the genetics of bone traits, 3) the influence of dietary factors on the skeleton, including the interaction between genes, diet and other environmental factors on bone density. The next five years will expand on these three themes using both previously collected data as well as new data to be generated.... This research is relevant to public health in several ways. First it will determine how muscle mass in the legs contributes to fracture risk. Second it will identify genes as well as nutritional factors such as the B-vitamins and dietary fat that work together to increase the risk for osteoporosis. (Complete description)

 

National Institutes of Health (NIH) RO1

Grant Number: 5R01AG025489-02

Project Title: Low Magnitude Mechanical Stimulation to Improve BMD (VIBES)

Principal Investigator: Douglas Kiel

Description:

The treatment options for osteoporosis, a major health complication in the aged population, are limited to pharmacologic interventions, the majority of which are antiresorptive. In this revised application, we propose to evaluate the efficacy of a unique, biomechanically based treatment for bone loss; low magnitude mechanical stimulation. .... For this study we have assembled a collaboration of internationally known experts in osteoporosis involving older persons, together with a respected and experienced coordinating center. Based on strong preliminary data, this study will provide new and important information about the role of low magnitude high frequency mechanical stimulation on the skeleton.

(Complete description)

 

Age Gene/Environment Susceptibility Study-Reykjavik

Principal Investigator: Vilmundur Gudnason

Description:

The sequencing of the human genome and identification of candidate genes will allow substantial innovation in the epidemiologic study of aging. Understanding genetic and environmental contributions could create novel opportunities to prevent disease and limit disability. To address this unique opportunity, the Age, Gene/Environment Susceptibility (AGES Reykjavik) Study was initiated to examine genetic susceptibility and gene/environment interaction as these contribute to phenotypes common in old age, a collaborative study between the National Institute on Aging, NIH and the Icelandic Heart Association. (Complete Description)

National Institutes of Health (NIH) RO1

Grant Number: 1R01HL088451-01A1

Project Title: Abdominal Body Composition, Inflammation and Cardiovascular Disease

Principal Investigator: Matthew Allison

Description:

Obesity is a burgeoning public health problem with the rates of this condition differing by age, sex and ethnicity. The distribution of abdominal fat also differs by ethnic group.... These differences have important implications for the interpretation of the ethnic-specific relationships between abdominal body composition, inflammation and incident cardiovascular disease events.... This will provide important physiologic and clinically relevant information on the potential therapeutic targets for interventions aimed at reducing CVD risk by altering the composition of fat in different compartments, including skeletal muscle. We are unaware of any other population-based study that is as comprehensive as this to study the stated aims. (Complete description)

 

NASA Spaceflight Research Project

Project Title: Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates)

Principal Investigator: Adrian Leblanc

Description:

The purpose of this investigation is to determine whether bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS flights.... The purpose of this study is not to test one dosing option versus the other. Rather, the intent is to show that bisphosphonates plus exercise will have a measurable effect versus exercise alone in preventing space flight-induced bone loss. (Fact Sheet)