# Determinants of bone microarchitectural compromise in youth with type 1 diabetes

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $300,207

## Abstract

PROJECT SUMMARY/ABSTRACT
The risk of fracture, particularly hip fracture, among people with type 1 diabetes (T1D) is 3 to 6-fold higher than
that of the general population. The increased risk of fracture starts as early as the first decade of life,
suggesting that T1D affects bone development in childhood. This is not surprising: childhood and adolescence
are critical periods for the development of the skeletal system, characterized by exuberant bone formation.
Approximately 90% of the adult skeleton is formed by late adolescence; therefore, a process that interferes
with bone formation in childhood has the potential to lead to profound and life-long effects. However, the
specific insults to the skeleton that predispose patients with T1D to fracture and the mechanisms underlying
these insults remain poorly understood. T1D-associated skeletal fragility is becoming an increasingly important
public health problem. With a rising incidence of T1D in the population as well as improvements in life
expectancy among patients with T1D due to improved treatment options, a larger number of T1D patients are
aging and will be at risk for diabetes-associated fragility fracture, conferring substantial morbidity and mortality.
The overall goal of this 2-year prospective observational study is to define the differences in bone development
and the factors that cause these differences in children and young adults with T1D ages 6-20 years compared
to their non-diabetic peers. Our preliminary data in pubertal girls demonstrate that trabecular bone density is
low and trabecular bone morphology is altered in T1D, and that those children with higher average blood
glucose as measured by HbA1c are more severely affected. In Aim 1, we will identify differences in bone mass,
microarchitecture, and strength in both boys and girls across the age spectrum of childhood to young
adulthood using second-generation high-resolution peripheral quantitative computed tomography. In Aim 2, we
will determine which glycemic parameters predict altered bone mass, microarchitecture, and strength using
continuous glucose monitoring to measure average glycemia, hyperglycemic time, and glucose variability. In
Aim 3, we will use validated questionnaires assessing bone loading activities as well as accelerometry to
determine to what extent the bone-forming response to physical activity is blunted in T1D. The Co-Principal
Investigators, Drs. Deborah Mitchell, Madhusmita Misra, and Mary Bouxsein, have complementary clinical and
research expertise in T1D, bone metabolism, and bone biomechanics. Data derived from this study will provide
critical knowledge about the specific bone alterations in T1D and their underlying mechanisms to enable the
development of targeted and effective therapies to prevent fragility fracture in this at-risk population.

## Key facts

- **NIH application ID:** 10465113
- **Project number:** 5R01DK122581-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** MARY L BOUXSEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,207
- **Award type:** 5
- **Project period:** 2019-09-12 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465113

## Citation

> US National Institutes of Health, RePORTER application 10465113, Determinants of bone microarchitectural compromise in youth with type 1 diabetes (5R01DK122581-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465113. Licensed CC0.

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