# Vascular Mechanisms Underlying Skeletal Fragility in Older Adults

> **NIH NIH R01** · HEBREW REHABILITATION CENTER FOR AGED · 2021 · $627,699

## Abstract

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, and (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.

## Key facts

- **NIH application ID:** 10120315
- **Project number:** 1R01AG065299-01A1
- **Recipient organization:** HEBREW REHABILITATION CENTER FOR AGED
- **Principal Investigator:** ELIZABETH J SAMELSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $627,699
- **Award type:** 1
- **Project period:** 2020-12-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120315

## Citation

> US National Institutes of Health, RePORTER application 10120315, Vascular Mechanisms Underlying Skeletal Fragility in Older Adults (1R01AG065299-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120315. Licensed CC0.

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