# Determining the Biological Mechanisms of Pathological Cortical Porosity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $280,691

## Abstract

SUMMARY
Cortical bone porosity is a major determinant of bone strength. In fact, age-related increases in cortical porosity
account for more than 75% of the concomitant reduction in cortical bone strength. Further, our group and
others have found that increased cortical porosity is associated with elevated fracture prevalence in patients
with type 2 diabetes (T2D). Despite the biomechanical importance of cortical porosity, the biological drivers of
cortical pore expansion are unknown. Filling this knowledge gap will elucidate appropriate cellular targets for
drug development to prevent or reverse pathological pore development and the associated skeletal fragility.
The biological systems influencing pore expansion can be revealed by visualizing the content of cortical pore
space. Our team has developed innovative magnetic resonance imaging (MRI)-based acquisition and
processing techniques to visualize vasculature and fat within cortical pores, both of which have been
implicated in pore expansion. We propose to detect new pore space formed over the course of a longitudinal
skeletal imaging study, identify the content of that new pore space, and in this way determine the biological
system(s) driving development of the new pore space. The proposed parent study is an ongoing longitudinal
study of cortical pore development in the context of T2D. The aim of the parent study is to quantify longitudinal
changes in cortical porosity in patients with T2D and in healthy controls. Further, the parent study applies our
MRI-based pore content visualization technique to the baseline time-point of the study (only) to compare pore
content between T2D and healthy cohorts and to evaluate associations between pore content and clinical
evaluations of vascular health and fat metabolism. The parent study does not include MRI at the follow-up visit,
and therefore will not be able to answer the question: In T2D and healthy controls, is the vascular system, the
marrow fat, or both responsible for increased cortical porosity over time? In this ancillary study, we will add the
MRI-based pore content visualization to the follow-up visit of the parent study. We will directly image the
content of pores that develop and/or expand over the 2-year follow-up period, and in this way reveal the
mechanisms associated with pore space expansion. By leveraging the parent study we capture a well-
characterized cohort, with all necessary clinical and imaging data already acquired, with the exception of the
follow-up MRI. This application meets the time sensitivity requirement of the funding announcement: in order to
efficiently leverage the established parent study cohort, the pore content visualization technique must be
added by early 2020. This work will identify the biological systems driving increased porosity associated with
aging and T2D, as well as potential drug targets for the prevention or reversal of age- and T2D-related
pathological porosity and bone fragility, laying the groun...

## Key facts

- **NIH application ID:** 9984813
- **Project number:** 1R01AR076159-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** GALATEIA J KAZAKIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $280,691
- **Award type:** 1
- **Project period:** 2020-09-02 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984813

## Citation

> US National Institutes of Health, RePORTER application 9984813, Determining the Biological Mechanisms of Pathological Cortical Porosity (1R01AR076159-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984813. Licensed CC0.

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