# The impact of glomerular disorders on bone quality and strength

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $669,248

## Abstract

PROJECT SUMMARY
Children and adolescents with glomerular disease have unique and potentially modifiable risk factors for
compromised bone health, but our current understanding of skeletal fragility in glomerular disease is lacking. In
the first large population-based cohort study, we recently found that primary glomerular disease was
independently associated with a >45% increased risk of incident spine and hip fracture, and that hip fracture risk
was >1.5-fold greater in patients younger vs. older than 40 years of age. Mechanisms that drive increased
fracture risk in glomerular disease are not clear but likely multifactorial. Our prior work in the Neptune cohort
demonstrated that glomerular disease is associated with disturbances in vitamin D and mineral metabolism, and
patients with glomerular disease are also exposed to medications which may negatively impact bone health.
Identifying modifiable factors that compromise bone strength will facilitate the development of strategies to
reduce fractures and other skeletal complications across the lifecourse. The primary objectives of this study are
to: (1) determine the impact of glomerular disease on bone strength and (2) investigate the pathophysiologic
underpinnings of impaired bone strength in glomerular disease. The proposed multi-center study will leverage
the infrastructure of the NIH-funded CureGN prospective cohort study and the resources of two health systems
[Children's Hospital of Philadelphia (CHOP)/University of Pennsylvania (Penn) and Columbia University Medical
Center] with expertise in state-of-the-art high-resolution bone imaging and biopsy methods, to conduct the first
prospective, longitudinal study to assess determinants of impaired bone quality and strength in glomerular
disease. 150 CureGN participants (100 adults/50 children) and 120 age-, sex-, race-, and body mass index-
matched healthy reference participants will be evaluated at baseline and 12 months. The new 2nd generation
high-resolution peripheral quantitative computed tomography (HR-pQCT) device will be used to assess bone
microarchitecture and generate micro-finite element analysis (µFEA) estimates of bone strength. We will also
determine the DXA measures of areal BMD and bone mineral content (whole body, spine, hip and radius) that
reflect bone deficits captured by HR-pQCT. Tetracycline double labeled transiliac crest bone biopsy specimens
will be collected from a subset of 40 adult CureGN participants and analyzed by 2D histomorphometry; by
microCT for 3D cortical and trabecular microarchitecture and estimated strength by finite element analysis; and
by Nanoindentation/Raman spectroscopy for bone mechanical and matrix-level characterization. Concurrent
clinical and biochemical profiling will allow for assessment of predictors of prospective changes in biomechanical
competence and cortical and trabecular microarchitecture by HR-pQCT as well as tissue-level bone matrix and
mechanical properties. The results of this stu...

## Key facts

- **NIH application ID:** 10226160
- **Project number:** 5R01DK119266-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Michelle Denburg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $669,248
- **Award type:** 5
- **Project period:** 2018-09-21 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226160

## Citation

> US National Institutes of Health, RePORTER application 10226160, The impact of glomerular disorders on bone quality and strength (5R01DK119266-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10226160. Licensed CC0.

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