# Development and Persistence of Tissue-Level Musculoskeletal Deformity Following Brachial Plexus Birth Injury

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2024 · $79,090

## Abstract

PROJECT SUMMARY
Brachial plexus birth injury (BPBI) is a traumatic perinatal neuromuscular injury causing muscle paralysis and
lifelong arm impairment. Muscle paralysis in these children also leads to bone and joint consequences, including
deformed growth of the scapula and humerus. BPBI occurs during a critical period of rapid musculoskeletal
growth, but the parallel postnatal interactions of muscle and bone that drive these persistent deformities are not
understood. Clinical reports and preliminary work suggest that short, contracted muscles after injury can alter
mechanical loading of the shoulder consistent with observed bone deformity at macro- and microstructural levels.
Altered active limb function with reduced range of motion and load bearing is also present; disuse is known to
alter tissue growth and maturation. Finally, nerve injury in other conditions also affects bone growth directly, and
direct effects in the postnatal period are not clear. Identifying appropriate targets for future treatment requires
understanding which factors associated with altered bone and muscle development are most critical for driving
altered growth. Almost nothing is known about the timing and progression of changes in underlying bone and
muscle structure or metabolism following nerve injury occurring at birth to provide a foundation for clinical
decision-making. Our primary hypothesis is that the bone deformity following BPBI is driven primarily by the
mechanical environment, derived from impaired longitudinal growth of paralyzed muscle and altered active
functional loading beginning shortly after injury. We will apply our unique rodent and computational models of
BPBI that probe the separate contributions of nerve injury and muscle contracture to perform complementary
assessments of the relative contributions of nerve injury, passive muscle loading, and active functional loading
following BPBI to bone deformity. We will do so using 1) previously validated rat neurectomy models of brachial
plexus injury and our unique disarticulation model of altered loading and 2) an integrated computational model
to determine which specific features of bone deformity following BPBI are driven primarily by each potential
driver. This R01 project, conducted by a multidisciplinary team with expertise in orthopedic surgery and
biomechanical engineering, has high potential to elucidate the role of denervation in the parallel development of
bone and muscle that occurs postnatally. Our innovative study design permits us to isolate both direct neural
effects and indirect effects from altered passive and active mechanical loading on bone development in a way
that has not previously been possible. Ultimately, this work has the potential to shift current research and
treatment paradigms from an isolated focus on muscle as a treatment target to an integrated muscle and bone
approach based on driving factors of deformity and loss of function. We anticipate our results will provide new...

## Key facts

- **NIH application ID:** 11043271
- **Project number:** 3R01HD101406-04S1
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Jacqueline H Cole
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,090
- **Award type:** 3
- **Project period:** 2021-03-10 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11043271

## Citation

> US National Institutes of Health, RePORTER application 11043271, Development and Persistence of Tissue-Level Musculoskeletal Deformity Following Brachial Plexus Birth Injury (3R01HD101406-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11043271. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*