# Progression and etiology of cortical porosity in diabetic bone disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $453,486

## Abstract

SUMMARY
Diabetic bone disease, with its elevated risk for fragility fracture, is increasingly recognized as a distinct entity
that cannot be assessed sufficiently with standard methods used for osteoporosis. Severe deficits in cortical
bone structure, specifically increased cortical porosity, are associated with fracture prevalence in T2D. Cortical
porosity has deleterious effects on bone strength, and is critical in fracture initiation and propagation. Despite
the biomechanical importance of cortical porosity, the origins and temporal evolution of pathological cortical
porosity in T2D are unknown. To develop treatments specifically targeted to the prevention or reversal of
pathological cortical porosity and associated bone fragility in T2D, we must understand the mechanisms driving
development of these large cortical pores. Today, these mechanisms are unknown though many have been
posited, including endocortical `trabecularization' and expansion of the Haversian network. We hypothesize
that determining the content and spatial distribution of cortical pore space will reveal biological systems
influencing pore expansion. Marrow within pores near the endosteal border may indicate endocortical
`trabecularization', or infiltration of the marrow cavity into the cortical envelope. Alternatively, vessels within
pores distributed throughout the cortex may indicate pore formation via expansion of the vascular network. The
identification of biological systems associated with pore expansion will elucidate appropriate cellular targets for
drug development. The overall goal of this proposed study is to understand the longitudinal evolution of human
diabetic bone disease and to investigate the underlying biological processes that drive increased cortical
porosity in the setting of T2D. We propose the first longitudinal study of pore progression in T2D patients,
which will be performed using a novel combined high-resolution peripheral quantitative computed tomography
(HR-pQCT) and contrast enhanced magnetic resonance (MR) imaging approach, with the following aims: I:
Determine if increased porosity in T2D is associated with altered marrow distribution and composition, II:
Determine if increased porosity in T2D is associated with altered vessel distribution and vascular health, and III:
Determine if T2D status or marrow or vessel metrics predict longitudinal increase in porosity and decrease in
strength. To address aims I and II, we will perform multimodal imaging in a cross-sectional cohort of T2D
patients and matched control subjects. To address aim III, we will follow these subjects in a 2-year longitudinal
study. This work will establish whether cortical pore content can serve as a predictor of future cortical
degradation, and begin to elucidate biological drivers and possible drug targets for the prevention or reversal of
T2D-associated pathological porosity and bone fragility, laying the groundwork for future therapeutic studies.
With the number of devasta...

## Key facts

- **NIH application ID:** 10146295
- **Project number:** 5R01AR069670-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** GALATEIA J KAZAKIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $453,486
- **Award type:** 5
- **Project period:** 2017-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146295

## Citation

> US National Institutes of Health, RePORTER application 10146295, Progression and etiology of cortical porosity in diabetic bone disease (5R01AR069670-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146295. Licensed CC0.

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