R01AG065299

Vascular mechanisms underlying skeletal fragility in older adults - The vascular supply is critically important to the skeleton, yet the clinical implications of vascular dysfunction for skeletal fragility are poorly understood. Studies demonstrate associations between vascular disease and osteoporosis in older adults. However, it is unknown whether vascular dysfunction itself underlies these associations.

We propose to use subclinical vascular tonometry and hemodynamic measures to test the hypothesis that vascular impairments negatively affect cortical bone microarchitecture, increasing fracture risk in the cortical-rich peripheral skeleton. Our preliminary data demonstrate that vascular changes are associated with increased fragility fractures and deficits in cortical bone microstructure, as assessed by high-resolution peripheral quantitative computed tomography (HR-PQCT).

These data provide strong rationale for our proposed work, particularly since no previous studies have comprehensively investigated mechanistic measures of blood flow in both large arteries and microcirculation in relation to skeletal fragility. Our long-term goal is to improve understanding of skeletal fragility in older adults to reduce the burden of fractures, by focusing on how aging-related changes in the vasculature affect the peripheral skeleton.

Our central hypothesis is that individuals with more severe aortic stiffness and blunted peripheral hyperemic flow response will have more severe deterioration in cortical bone microarchitecture, loss of bone strength, and higher incidence of fracture. Advanced imaging techniques, such as HR-PQCT, provide volumetric skeletal compartment-specific measures of volumetric bone density and microarchitecture, while non-invasive vascular tonometry and hemodynamics lend key insight into the origins of large artery and microvascular deficits.

Together, these innovations provide necessary tools to advance knowledge of the vascular mechanisms underlying skeletal fragility and will identify novel targets for fracture prevention. Thus, in the unique setting of the Framingham Heart Study, we will address the following specific aims:

(1) Determine the contribution of vascular function to incidence of fracture.
(2) Determine the contribution of vascular function to longitudinal changes in bone density, microarchitecture, and strength.

Using state-of-the-art assessments of vascular dysfunction and cortical bone deficits, the investigative team has the experience and complementary areas of expertise to successfully carry out the specific aims. By identifying the vascular mechanisms underlying skeletal fragility, this project has the potential to be paradigm-shifting, providing new targets for interventions to reduce the tremendous public health burden of fractures in our older population.

Hebrew Rehabilitation Center

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Massachusetts United States

State-Wide

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the End Date has been extended from 11/30/25 to 11/30/26 and the total obligations have increased 396% from $627,699 to $3,114,001.