# Treating bone deterioration associated with chronic kidney disease

> **NIH VA I01** · RLR VA MEDICAL CENTER · 2024 · —

## Abstract

The prevalence of chronic kidney disease (CKD) in our veterans is putting them at elevated risk of fracture and
fracture-associated death. Nearly 1 of every 3 veterans has CKD, fracture risk in persons with CKD is 4x
higher than the age-matched general population, and persons who fracture with CKD have longer
hospitalization and higher mortality rates than patients without CKD who fracture. Simply stated, interventions
aimed at reducing CKD-associated fracture would have a significant impact on veteran health. Skeletal fragility
in CKD is unique from conditions such as osteoporosis. The hallmark of CKD-associated bone change is that
cortical bone develops porosity (holes) and also has clear changes to bone material properties Moving forward,
approaches to reduce skeletal fragility in CKD will need to address both reversal of cortical porosity and
improvements in material properties. The goal of this proposal is to provide foundational data on cortical bone
infilling in the setting of CKD. We will test the overall hypothesis that reversal of cortical porosity with enhanced
material quality can combine to improve bone mechanical properties in CKD. To achieve this goal we will use
two complementary animal models of kidney disease, one, the Cy/+ rat, to allow dynamic tracking of porosity
changes over time. The second, an adenine-induced model, to allow sex-based differences in porosity
dynamics and treatment efficacy to be studied. Both of these models have parallels the human disease in its
development of disturbed mineral homeostasis and bone fragility. This means the results from this work will
have high translational capacity to the clinic. In Aim 1 we will determine the effectiveness of suppressing bone
resorption with and without simultaneous PTH suppression on cortical porosity infilling in CKD. Two clinically-
relevant approaches will be studied – cinacalcet (to reduce parathyroid hormone) and
bisphosphonate (to reduce osteoclastic bone resorption). Using two complementary animal models of
CKD that develop robust cortical porosity, we will treat both male and female animals with either low-dose
bisphosphonate or cinacalcet. Key outcomes will be cortical porosity, using repeated in vivo microCT scans,
combined with a novel analysis approach that permits tracking of individual cortical pores over time. These
experiments will help us to understand how pore infilling occurs using clinical approaches and how this may
differ between sexes. In Aim 2 we will determine the effects of porosity infilling on tissue and structural
mechanical properties. Tissues from Aim 1 will be measured with Raman spectroscopy and nano-indentation
to characterize the mineral and collagen properties/mechanics of the newly infilled pore tissue. Whole bone
mechanical properties (monotonic and fracture toughness) will be used to assess overall bone properties as
surrogate measures of fracture resistance. Finally, in Aim 3 we will determine if combination treatment,
targetin...

## Key facts

- **NIH application ID:** 10767825
- **Project number:** 5I01BX003025-08
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** Matthew R Allen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767825

## Citation

> US National Institutes of Health, RePORTER application 10767825, Treating bone deterioration associated with chronic kidney disease (5I01BX003025-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10767825. Licensed CC0.

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