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.

Public Health Relevance

Total knee arthroplasty (TKA) surgery will increase dramatically in the coming decades, reflecting growth in the older adult knee osteoarthritis (OA) population. Although TKA effectively relieves joint pain, it does little to improve objectively-assessed physical functional capacity because of marked reductions in lower extremity neuromuscular function that occur during the early, post-surgical period. The proposed studies are relevant to public health because they seek to define the skeletal muscle adaptations that occur in TKA recipients during this early, post-surgical period and to explore interventions to counteract these adaptations, with the goal of improving physical functional capacity, reducing long-term disability and improving health outcomes in the older adult knee OA population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG050305-04
Application #
9712858
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Joseph, Lyndon
Project Start
2016-09-01
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405