# Mechanisms of chronic kidney disease-induced cortical porosity

> **NIH NIH F32** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $65,310

## Abstract

ABSTRACT
Chronic kidney disease (CKD) results in dramatic cortical porosity, a unique and devasting form
of bone loss, which is associated with high fracture rates leading to increased hospitalization and
mortality in patients. The cellular drivers of CKD-induced cortical porosity remain unexplored.
Concurrent with declines in kidney function are disruptions in mineral metabolism often leading to
chronically high parathyroid hormone (PTH) which has been associated with elevated bone
porosity. The goal of this training proposal is to test the global hypothesis that chronic elevations
in PTH affects osteocytes (lifespan and secretion of osteoclastic mediators) to promote porosity.
We aim to test this hypothesis using tissues from two animal models of CKD, human bone biopsy
samples, and in vitro cultures of bone. In Aim 1, we will quantify osteocyte apoptosis and RANKL
across various disease stages in CKD rodents and human bone biopsies and relate these
changes with cortical porosity and serum PTH. In Aim 2, we will suppress PTH with etelcalcitide,
a calcium sensing receptor agonist, and note the effects on porosity, osteocyte apoptosis, and
RANKL. This will be done in both animals and in humans. Finally, utilizing rat bone primary
cultures, we will administer CKD serum with and without a PTH-blocker as well as PTH alone to
examine the direct/indirect effects of PTH in the setting of CKD on osteocyte RANKL and
apoptosis. Together this combination of basic, translational, and clinical studies will enhance our
knowledge of the drivers of cortical porosity in CKD and address the mechanisms of current
therapeutic targets to improve bone health in patients with CKD. In addition, it presents an ideal
training environment to enhance the applicant’s skills in basic, translational, and clinical work.

## Key facts

- **NIH application ID:** 10053680
- **Project number:** 5F32DK122731-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Corinne Metzger
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-09-25 → 2022-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053680

## Citation

> US National Institutes of Health, RePORTER application 10053680, Mechanisms of chronic kidney disease-induced cortical porosity (5F32DK122731-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10053680. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*