# Improving bone mass and quality in comorbid diabetes and chronic kidney disease

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

## Abstract

PROJECT SUMMARY
Diabetes and chronic kidney disease (CKD) consistently rank among the top ten chronic conditions in the United
States in terms of prevalence and mortality. US veterans develop diabetes and CKD at an alarming rate, and
comorbidity is twice as common in veterans compared with the general population. Both diseases put patients
at increased risk of fracture and when fractures occur, patients are at a greater risk of death compared to other
populations. Treatments for skeletal disease typically address deficits in either bone mass or tissue quality, which
may be insufficient in cases of combined CKD and diabetes where there are known deficits in both. Despite their
increasing comorbidity and well-established detrimental impacts on the skeleton, their skeletal interaction
remains unexplored due to a lack of combined disease animal models and routine exclusion of patients with
diabetes and/or CKD from clinical drug trials. The goal of this project is to study skeletal interactions between
diabetes and CKD and to identify effective combination skeletal treatments. Using our novel combined model of
diabetes and CKD, we will test the central hypothesis that increasing bone mass while concurrently improving
tissue quality using combined therapies will increase bone mechanical strength, improve fracture resistance, and
reverse adverse skeletal effects of late-stage diabetes+CKD. To achieve this goal, we will use our novel
combined model of diabetes and CKD to investigate molecular, biochemical, and compositional changes coupled
with multiscale structural and mechanical properties. Aim 1 will investigate the effects of combined disease as a
function of age of onset and disease duration. Our lab has established a combined model of diabetes
(streptozotocin) and CKD (adenine) that uniquely alters skeletal properties in young mice. 4 experiments will be
used, inducing disease in either young or aged mice, and then allowing disease to progress for a short or longer
duration. Key outcomes will include longitudinal insulin and glucose monitoring, HbA1c, insulin and glucose
tolerance tests, pancreatic beta cell mass, and renal biochemistries. Skeletal outcomes will include biochemical
markers of turnover and disease, structural imaging, bone formation/resorption histology, and a suite of
multiscale mechanical and compositional properties. These experiments will clarify how diabetes and CKD
impact the skeleton as a function of sex, age, and disease duration. In Aim 2, we will determine the skeletal
impacts of treatment in late-stage disease utilizing mechanical loading (to improve bone mass) and Raloxifene
(RAL – to improve tissue hydration and quality). We have shown that RAL, an FDA-approved agent for treating
bone, specifically benefits bone material properties in a cell- and estrogen-independent manner. End points will
be the same as those in Aim 1, including colocalized Raman spectroscopy and nanoindentation to characterize
the mineral and collage...

## Key facts

- **NIH application ID:** 10773110
- **Project number:** 5I01BX005990-02
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** Joseph Michael Wallace
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773110

## Citation

> US National Institutes of Health, RePORTER application 10773110, Improving bone mass and quality in comorbid diabetes and chronic kidney disease (5I01BX005990-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10773110. Licensed CC0.

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