# Diabetes-Related Changes Affecting Bone Quality

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Project Summary/Abstract:
The risk of bone fracture and subsequent high morbidity increases with the progression of type 2 diabetes (T2D),
and the clinical assessment of bone mineral density (BMD) is not particularly effective in diagnosing this risk.
Moreover, lowering fracture risk among patients with T2D requires an understanding of the changes in the bone
that affect fracture resistance. Addressing these unmet needs, the proposed project aims i) to determine the
primary biomechanical reason for the increase in fracture risk with T2D, ii) to identify molecular changes in the
bone matrix that can significantly affect fracture resistance, and iii) to ascertain the ability of matrix-sensitive tools
to assess significant differences in bone quality between age-matched non-diabetics and diabetic individuals. In
Aim 1, cadaveric bone from non-diabetic and T2D donors matching for age and gender will be comprehensively
analyzed to determine whether the primary T2D-related decrease in fracture resistance is lower bone toughness,
lower fatigue resistance, and/or lower fracture toughness as opposed to lower strength at the whole-bone- and
material-level. Moreover, the ability of matrix characteristics to explain T2D-related differences in these
mechanical properties of bone will be assessed in relation to volumetric BMD and micro-structure (assessed by
micro-computed tomography) as well as the degree of mineralization and osteonal density (assessed
backscattered electron imaging). Matrix characteristics will include secondary structure of collagen I as
determined by sub-peak ratios of the Amide I band from Raman spectroscopy (RS), bound and pore water
volume fractions as determined by proton nuclear magnetic resonance (NMR) relaxometry, and resistance to
microindentation properties as determined by both cyclic and impact reference point (RPI). In Aim 2, the focus
will be on the contribution of novel molecular mechanisms to the underlying diabetic changes in matrix-bound
water and collagen structure. Specifically, emphasis will be placed on post-translational modifications (PTMs) of
collagen I and non-collagenous bone matrix proteins as a mechanism that affects hydrogen bonding between
water and the matrix. Implicated in diabetes, these PTMs will include non-enzymatic advanced glycation end
products (AGEs) as well as enzymatic hydroxylation, glycosylation, and carboxylation. In Aim 3, matrix-sensitive,
clinical techniques will determine whether bone quality is significantly different between patients without diabetes
and patients with established T2D. By matching age and BMD-derived T-scores between the groups, we will
ascertain whether bone material strength index from impact RPI, bound and pore water concentrations from
ultra-short time-to-echo magnetic resonance imaging (UTE-MRI) of NMR signals (T2), and Amide I sub-peak
ratios from spatially offset, transcutaneous RS, all acquired at the tibia mid-shaft, will potentially add value to the
clinical asse...

## Key facts

- **NIH application ID:** 10155432
- **Project number:** 5I01BX004297-03
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Jeffry Stephen Nyman
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155432

## Citation

> US National Institutes of Health, RePORTER application 10155432, Diabetes-Related Changes Affecting Bone Quality (5I01BX004297-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10155432. Licensed CC0.

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