# The Effect of Etelcalcetide on Bone-tissue Properties in End Stage Kidney Disease

> **NIH NIH F30** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $51,036

## Abstract

ABSTRACT
Chronic kidney disease (CKD) patients are at an alarming risk of fracture-related mortality. The progression of
CKD is marked by abnormal biochemistries including disrupted mineral homeostasis and elevated parathyroid
hormone (PTH), or hyperparathyroidism (HPT). Chronic HPT is currently thought to be responsible for the
dramatic loss of bone mass and increased fracture risk in CKD patients, and thus patients have PTH levels
monitored to determine their fracture risk. Further, these patients are commonly given PTH-lowering drugs
including calcimimetics. These drugs act by sensitizing the calcium-sensing receptor in parathyroid chief cells,
lowering their PTH secretion. While these drugs have been shown to reduce fracture risk in CKD patients on
dialysis, there is little known about their effect on bone mass and quality. Interestingly, CKD patients with normal
bone mass and controlled PTH levels remain at an increased fracture risk. Thus, there is a critical gap in our
understanding of what skeletal properties dictate bone strength in both the disease process and treatment of
CKD bone disorder. Recently, there has been increasing recognition of the role of bone quality in determining
overall bone strength. Bone quality refers to a combination of bone architecture, chemical composition of the
bone matrix, and the resulting whole bone and tissue-level mechanical properties. To date, however, measures
of bone quality in the setting of CKD and calcimimetic treatment have not been spatially matched, or colocalized,
in bone samples of known tissue age. Based on the above scientific premise, the goal of this proposal is to test
the hypothesis that calcimimetic drugs reduce fracture risk by improving bone quality. Specifically, this study will,
in addition to measuring changes in bone architecture, spatially match measures of matrix composition and
tissue-level mechanical properties before and after calcimimetic treatment. The first Aim is to determine the
effects of calcimimetic treatment on matrix composition and mechanical properties in the Cy/+ rat, a slowly
progressive model of CKD. This will be accomplished by running colocalized Raman spectroscopy to determine
matrix composition and nanoindentation to determine tissue-level mechanical properties on rat femur sections.
Fluorescent labels will be given before and after treatment to identify regions of bone formed at each time point
and to control for tissue age. Outcomes will include semi-quantitative measurements of mineral and matrix
content, crystallinity, and carbonate content as well as measurements of tissue hardness and stiffness. For the
second Aim, a similar study will be accomplished using transiliac crest bone biopsies from CKD patients with
severe HPT. Specimens will again be controlled for tissue age and will undergo colocalized Raman spectroscopy
and nanoindentation. Data from the above Aims will allow us to generate novel correlations between alterations
in bone matrix properti...

## Key facts

- **NIH application ID:** 10158482
- **Project number:** 5F30DK121399-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** John  Damrath
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158482

## Citation

> US National Institutes of Health, RePORTER application 10158482, The Effect of Etelcalcetide on Bone-tissue Properties in End Stage Kidney Disease (5F30DK121399-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10158482. Licensed CC0.

---

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