# The efficacy of β-aminoisobutyric acid myokine to reduce bone loss after spinal cord injury

> **NIH VA I21** · JAMES J PETERS VA  MEDICAL CENTER · 2021 · —

## Abstract

Veterans with chronic motor complete spinal cord injury (SCI) invariably have had bone loss and resultant
severe sub-lesional osteoporosis and increased fragility fractures. Currently, there is no widely accepted or
proven treatment for osteoporosis in non-ambulatory patients with SCI. The efficacy of anti-resorptive agents in
the treatment of those with acute SCI has been questioned and ineffective. As a result, there is an urgent need
to develop new therapeutic strategies to prevent bone loss and enhance bone quality after sustaining a SCI.
The primary objective of this proposal is to determine the efficacy of a recently-discovered muscle factor or
myokine named β-aminoisobutyric acid (BAIBA) on reducing bone loss after chronic SCI. BAIBA has been
shown to exhibit potent osteogenic properties and to prevent bone loss in tail suspended mice, a model of
unloading bone loss. Furthermore, BAIBA produced its favorable osteogenic properties by inhibiting, in
osteocytes, oxidative stress and improving mitochondrial function. Importantly, our preliminary findings
demonstrate that osteocytes from bones of SCI mice exhibit impaired mitochondrial function and increased
oxidative stress. Accordingly, we propose to test the hypothesis that BAIBA administration will restore
osteocyte function thus reducing bone loss after chronic SCI. In our study aim, we will elucidate the effects of
oral administration of vehicle and different doses of BAIBA on restoring bone mineral density (BMD) and
structure in mice after chronic SCI. BAIBA will be administered to 20 week old C57BL/6J wild type male and
female sham or SCI mice in drinking water at 0, 50, 100, or 500 mg/kg/day. Treatment will start 35 days after
SCI and will continue for 35 days when animals will be sacrificed. Endpoint analyses will include measurement
of BMD by Dual energy x-ray absorptiometry (DXA) scanning and bone structure and microarchitecture by
microcomputed tomography scanning (Micro-CT). Biochemical analysis of bone turnover markers and factors
will also be performed on collected sera and bone marrow (BM) supernatants using specific ELISA.
Mechanistically, the effects of BAIBA treatment on oxidative stress will be evaluated on BM supernatants and
osteocyte-enriched bone extracts of SCI and control mice using specific oxidative stress assays. The project is
expected to identify the optimal therapeutic dose of BAIBA that will attenuate the deleterious effects of
immobilization on the skeleton of SCI animals. This application has the potential of discovering a new
therapeutic strategy that may overcome the challenge of severe osteoporosis in Veterans with SCI specifically
many years after injury. We propose the following specific aim:
Aim: To determine the effects of BAIBA on restoring skeletal integrity after chronic SCI.

## Key facts

- **NIH application ID:** 10257699
- **Project number:** 1I21RX003756-01
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** HESHAM A TAWFEEK
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10257699

## Citation

> US National Institutes of Health, RePORTER application 10257699, The efficacy of β-aminoisobutyric acid myokine to reduce bone loss after spinal cord injury (1I21RX003756-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10257699. Licensed CC0.

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