# Osteoarthritis After ACL Injury: Establishing Cumulative Joint Loading as a Preventative Target

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $166,954

## Abstract

Project Abstract
Each year in the United States, a quarter million individuals will severely injure their anterior cruciate ligament
(ACL), and half will develop radiographic signs of knee osteoarthritis (OA) within ten years. Unfortunately,
evidence-based interventions to prevent post-traumatic knee OA do not yet exist. Changes in joint structure
and function that are linked to radiographic knee OA occur quickly after ACL injury, particularly 1) alterations in
articular cartilage matrix organization on quantitative magnetic resonance imaging (MRI) within two months
after ACL reconstruction, 2) abnormal joint unloading early after ACL injury and six months after ACL
reconstruction, and 3) self-reported poor knee function before ACL reconstruction. Insufficient physical activity
levels play a role in OA in older adults, but their influence in progression to post-traumatic OA is unknown,
particularly in combination with joint loading. Understanding these early changes and relationships between
physical activity levels and movement patterns with later joint outcomes (articular cartilage breakdown, knee
function) is critical for future development of interventions to hinder progression to OA. The purpose of this
study is to identify markers that predict the earliest signs of poor joint outcomes after ACL injury. We will
measure daily physical activity through accelerometry (step counts) and biomechanical function (peak knee
moments during loading phase of gait) in participants within one month of ACL injury and again at two, four,
and six months after ACL reconstruction. Participants will complete MRI testing at baseline and six months
after ACL reconstruction to determine changes in the articular cartilage microstructure (measured by T2
relaxation time). Knee function will be measured by the Knee injury and Osteoarthritis Outcome Score (KOOS)
at six months after ACL reconstruction. In Aim 1, we will determine how physical activity levels and
biomechanical function before and after ACL reconstruction relate to changes in T2 relaxation time at 6 months
after ACL reconstruction. Cumulative joint loading (product of mean steps per day and knee flexion moment)
will be tested against individual physical activity and biomechanical factors to determine the strongest joint
loading determinant of T2 relaxation time. In Aim 2, we will identify levels of daily physical activity that predict
poor post-operative knee function on the KOOS. This work will define movement biomarkers that predict early
changes in cartilage microstructure (Aim 1) and post-operative knee joint function (Aim 2) after ACL injury.
Successful completion of this study will result in identification of an initial target or range of healthy knee joint
loading levels after ACL injury. Our findings will provide a foundation to test the efficacy of different regimens
aimed at optimizing joint loading to reduce degenerative changes in articular cartilage following ACL injury. We
predict that these...

## Key facts

- **NIH application ID:** 10114217
- **Project number:** 5R21AR075254-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Elizabeth A Wellsandt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $166,954
- **Award type:** 5
- **Project period:** 2020-02-25 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114217

## Citation

> US National Institutes of Health, RePORTER application 10114217, Osteoarthritis After ACL Injury: Establishing Cumulative Joint Loading as a Preventative Target (5R21AR075254-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10114217. Licensed CC0.

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