# Quantifying the contribution of collagen cross-linking to increased bone fragility

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $136,400

## Abstract

PROJECT SUMMARY
Over the last decades, the drastic rise in sugar consumption, lack of activity and socio-economic factors has led
to a rapid increase in obese and type 2 diabetic populations. Diabetic adults have double the risk of fracture
compared with non-diabetic adults with a similar bone mass. If it is becoming clear that high blood glucose affects
bone quality and is involved in fragility fracture, the pathogenesis and mechanisms of increased fracture risk in
T2D are not well understood. Our recent findings in a diabetic rat model indicate that brittle behavior in type 2
diabetic bone was primarilty due to a substantial reduction in collagen capacity of deformation rather than change
in bone structure. This is thought to be associated with the increase of specific non-enzymatic cross-links known
as Advanced Glycation End products (AGEs), preventing the collagen molecules to slide onto each other.
However, the independent influence of AGEs cross-links on the whole-bone resistance to fracture is unknown.
The overall objective of this project is to characterize the collagen nanoscale behavior to establish the role of
AGE collagen crosslinks on the whole-bone mechanical behavior and bone fragility in T2D. We propose to
identify these mechanisms by combining multiscale numerical modeling with dedicated experimentation.
Realistic molecular-scale numerical models of mineralized collagen fibrils and finite element models will be used
to establish the effect of AGEs concentration on whole-bone resistance. Synchrotron and AFM experiments will
then be used to test bone’s behavior at each length scale with different AGEs concentration (achieved via
ribosylation) to validate our numerical models and quantify collagen deformation as a function of whole-bone
deformation. This new multiscale model will establish a new quantitative understanding of the mechanisms by
which changes at the collagen level of cortical bone increase bone fracture risk in the diabetic population,
ultimately identifying a novel pathway to prevent and treat fracture in diabetic patients.

## Key facts

- **NIH application ID:** 10448298
- **Project number:** 5R21AR077881-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Claire Acevedo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $136,400
- **Award type:** 5
- **Project period:** 2021-07-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448298

## Citation

> US National Institutes of Health, RePORTER application 10448298, Quantifying the contribution of collagen cross-linking to increased bone fragility (5R21AR077881-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10448298. Licensed CC0.

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