# Does aging decrease osteocyte lacunar-canalicular bone quality?

> **NIH NIH R03** · MONTANA STATE UNIVERSITY - BOZEMAN · 2021 · $72,000

## Abstract

Project Summary
Bone fracture is common in aging, yet therapies for maintaining bone quality in aging are limited. The
osteocyte participates in bone quality maintenance and may be a promising therapeutic target for bone fragility
in aging. Osteocytes reside within bone in lacunae that are connected by canaliculi. The osteocyte can both
resorb and deposit bone tissue adjacent to the immense lacunar-canalicular system (LCS). Aging diminishes
the number and size of lacunae and canaliculi and also changes several aspects of osteocyte behavior.
However, these changes in lacunar and canalicular morphologies do not reveal how the fraction of osteocytes
engaged in bone resorption or deposition change in aging. Likewise, changes to the amount of remodeled
bone near lacunae and canaliculi due to aging are not known. Thus, there are critical gaps in the
understanding of how aging impacts osteocyte-mediated bone quality. The overarching hypothesis of this work
is that LCS remodeling increases bone quality by decreasing bone mineral and matrix maturity near
osteocytes, and that with increased age, less osteocytes participate in LCS remodeling. One Aim is proposed
to investigate this hypothesis. Femurs from skeletally-mature young adult (6 mo), middle-age (18 mo), and
aged (24 mo) female and male C57Bl/6 mice will be studied for lacunar-canalicular remodeling characteristics.
The fraction of osteocytes participating in bone mineral and matrix resorption will be evaluated from histology
and immunohistochemistry, while the fraction of bone-forming osteocytes will be assessed by measuring
lacunae positive for fluorochrome labels. For each age, mineral and matrix will be mapped for bone-forming
and non-bone-forming osteocyte lacunae using Auger Electron Spectroscopy (AES) at submicron resolution.
Complementary submicroscale-resolution Atomic Force Microscopy (AFM) maps of the same lacunae will
identify the impact of osteocyte remodeling on bone tissue modulus. AES and AFM maps will also be
generated for canaliculi. Osteocyte lacunar and canalicular morphologies will be measured for the same
femurs. Completion of this project will significantly advance the understanding of how osteocytes remodel bone
across the lifespan. The project will also answer the question of whether changes to osteocyte lacunar and
canalicular geometries in aging is associated with loss of bone quality near the osteocyte. The innovative use
of Auger Electron Spectroscopy and complementary Atomic Force Microscopy will provide new insights into
how aging changes bone quality at physiologically-relevant resolution adjacent to the lacunar-canalicular
system. This approach is expected to have broad utility for evaluating the impacts of disease, injury, and
therapeutics on osteocyte-mediated bone quality. The long-term goal of this research is to investigate whether
osteocyte behavior can be changed through therapeutic interventions to influence LCS remodeling and
improve skeletal fracture resist...

## Key facts

- **NIH application ID:** 10218921
- **Project number:** 1R03AG068680-01A1
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** Chelsea Marie Heveran
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218921

## Citation

> US National Institutes of Health, RePORTER application 10218921, Does aging decrease osteocyte lacunar-canalicular bone quality? (1R03AG068680-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10218921. Licensed CC0.

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