# Research Project Core 1

> **NIH NIH P50** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $105,035

## Abstract

PROJECT 1 ABSTRACT
Urinary stone disease (USD) is common and increasingly recognized as a chronic systemic disorder with skeletal
and vascular morbidity. Recent population-based data suggest this morbidity starts, and may even be more
pronounced, early in the lifecourse. The incidence of USD is increasing disproportionately among adolescents,
making it critical to understand its impact on bone and vascular health in this population. Furthermore, studies
of the bone-vascular link in USD are limited in adults and lacking in children, and the study of children confers
advantages in mitigating against confounding co-morbid conditions that are highly prevalent among adults.
Identifying modifiable factors that compromise bone strength and vascular health will facilitate the development
of strategies to reduce fracture rates and cardiovascular events across the lifecourse. The primary objectives of
this study are to: (1) evaluate the impact of USD on gains in bone density, structure and strength in adolescents
and identify modifiable predictors of changes in bone strength via urine metabolic profiling and dietary
assessment and (2) determine if USD is associated with subclinical vascular disease and if markers of vascular
disease are associated with lower bone strength in adolescents with USD.
The proposed work will leverage the resources of our multidisciplinary Pediatric Kidney Stone Center, combined
with state-of-the-art bone imaging methods and vascular measures, to conduct the first prospective cohort study
of bone quality and early markers of vascular disease in 125 adolescents (10-19 years old) with USD and 125
healthy controls matched on age, sex, and body mass index, followed over a 24 month interval. The new 2nd
generation high-resolution peripheral quantitative computed tomography (HR-pQCT) device will be used to
assess bone microarchitecture and micro-finite element analysis (µFEA) estimates of bone strength (failure load)
that are highly correlated with ex vivo biomechanical testing. Vascular assessment will combine markers of
arterial stiffness (pulse wave velocity/analysis), subclinical atherosclerosis (carotid intima-media thickness), and
endothelial function (EndoPAT), all of which have been shown to independently predict cardiovascular events in
adults. We will also determine if DXA measures of areal BMD and bone mineral content at multiple sites (whole
body, spine, hip and radius) reflect bone deficits captured by HR-pQCT and correlate with markers of vascular
disease. This will be the first study to perform repeated bone and vascular measures prospectively in adults or
children with USD. Concurrent longitudinal urine metabolic profiling by Litholink, three day 24-hour dietary
recalls, and comprehensive measures of vitamin D-related mineral metabolism will allow for assessment of
predictors including urine calcium, citrate, and uric acid excretion, dietary calcium, sodium and protein intake,
and altered vitamin D and mineral homeostas...

## Key facts

- **NIH application ID:** 10241469
- **Project number:** 5P50DK114786-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Michelle Denburg
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $105,035
- **Award type:** 5
- **Project period:** 2017-09-18 → 2022-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241469

## Citation

> US National Institutes of Health, RePORTER application 10241469, Research Project Core 1 (5P50DK114786-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241469. Licensed CC0.

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