# Modulating Cellular Bioenergetics to Improve Skeletal Health

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $220,330

## Abstract

PROJECT SUMMARY/ ABSTRACT
The long-term goal of my research program is to develop a comprehensive understanding of how metabolic
pathways impact bone health. Consistent with this goal, our vision is to apply strategies to identify novel
biological mechanisms, which lead to the development of new treatments that can improve the quality of life for
patients with bone fragility.
Osteoporosis and osteopenia are late-onset diseases affecting a staggering 54 million people in the U.S
addition to the financial burden, osteoporosis-related fractures often lead to multiple comorbidities which
significantly reduce longevity. While anabolic agents that increase bone formation, such as parathyroid
.
In
hormone (PTH), have aided in the management of osteoporosis, patients still experience adverse side-effects.
Therefore, continued development of refined therapeutic options is necessary. Relative to this, the current
project aims to harness PTH’s ability to modulate osteoblast bioenergetic capacity to promote bone formation
by supplying energy fatty acid substrates to meet this demand. Targeting metabolic pathways in bone cells is a
highly provocative tool that can be applied to combat various musculoskeletal conditions which lead to
increased fracture incidence (i.e., post-menopausal osteoporosis and age-related osteoporosis). Within this
scope, the current project aims to explore the osteo-anabolic effects of intermittent parathyroid hormone (iPTH)
via modulation of lipid metabolism on cells within the skeletal niche. Therefore, the overarching hypothesis is
that the osteoanabolic actions of iPTH can be enhanced by supplying osteoblasts with exogenous fatty acids.
This hypothesis will be tested in two specific aims. The first aim will utilize in vivo model systems to determine
whether manipulation in the availability of exogenous fatty acids influences iPTH-induced bone formation. The
second aim will further demonstrate that PTH-induced alterations in osteoblast activity rely on increased
adenosine triphosphate (ATP) production via fatty acid oxidation using a novel in vitro method. This project is
expected to have substantial health-related influence. Specifically, data generated from this project are likely to
translate directly to improve clinical outcomes by (1) identifying a novel bone anabolic mechanism, (2) aid in
the optimization of dosing strategy and/or efficacy of a current FDA-approved bone anabolic agent to prevent
osteoporotic-related fracture, as well as (3) lead to the identification of other pharmaceutical therapies
exploiting similar mechanisms, all of which are directly related to improving musculoskeletal health.

## Key facts

- **NIH application ID:** 10527457
- **Project number:** 1R21AR080387-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Elizabeth Rendina-Ruedy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $220,330
- **Award type:** 1
- **Project period:** 2022-07-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527457

## Citation

> US National Institutes of Health, RePORTER application 10527457, Modulating Cellular Bioenergetics to Improve Skeletal Health (1R21AR080387-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10527457. Licensed CC0.

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