# Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $434,891

## Abstract

Project Summary
Total knee arthroplasty (TKA) is currently the most common elective surgery in the US and will increase in
frequency nearly five-fold by 2030 to 3.5 million surgeries annually. This surgery is most prevalent among
older adults with advanced knee osteoarthritis (OA) and its increase is explained primarily by growth in this
population. Although TKA reliably reduces joint pain, it fails to correct objectively-measured functional
disability due, in part, to dramatic declines in lower-extremity neuromuscular function during the early, post-
surgical period. These deficits are never fully remediated, remaining for years after surgery and contributing
to persistent disability. Despite these detrimental effects of TKA, the fundamental skeletal muscle
adaptations that occur in the early, post-surgical period are poorly defined and understudied and there is
currently no widely-accepted, evidence-based intervention to counter these changes. To address this clinical
problem, our goals in this application are to define the skeletal muscle structural and functional adaptations
following TKA at the whole body, tissue, cellular, organellar and molecular levels in humans in an effort to
identify factors contributing to functional disability and to assess the utility of neuromuscular electrical
stimulation (NMES) to counter post-surgical muscle adaptations at these same anatomic levels. Based on
our preliminary data, we propose a hypothetical model in which TKA fails to remediate physical disability in
patients, in part, because of the profound skeletal muscle myofilament and mitochondrial loss and
dysfunction that develops during the early, post-surgical period. Moreover, we posit that NMES will improve
functional recovery following TKA by countering these early skeletal muscle adaptations. To test this model,
we will evaluate knee OA patients prior to and following TKA for skeletal muscle structure and function at
multiple anatomic levels, with patients randomized to receive NMES or sham control intervention during the
first 5 weeks post-surgery. We anticipate that our results will yield seminal, mechanistic knowledge of the
early, post-surgical skeletal muscle structural and functional adaptations to TKA, which will challenge
conventional thinking in this field and provide novel targets for rehabilitative and pharmacological
intervention. Additionally, our results will provide mechanistic evidence for the utility of NMES to prevent
deleterious post-surgical adaptations in skeletal structure and function. Our findings, therefore, hold the
potential to advance both basic scientific knowledge and clinical practice towards the goal of improving long-
term functional and health outcomes in knee OA patients, the most disabled sector of the older adult
population.

## Key facts

- **NIH application ID:** 9939412
- **Project number:** 5R01AG050305-05
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** MICHAEL J TOTH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,891
- **Award type:** 5
- **Project period:** 2016-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939412

## Citation

> US National Institutes of Health, RePORTER application 9939412, Skeletal Muscle Atrophy and Dysfunction Following Total Knee Arthroplasty (5R01AG050305-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9939412. Licensed CC0.

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