Total knee replacement, or arthroplasty, is the final clinical intervention available to relieve pain and functional limitations related to advanced stage knee osteoarthritis. Despite its beneficial effects, the early post-surgical period is characterized by the erosion of lower extremity muscle size and strength that cause further disability and slow functional recovery. While the detrimental effects of this period on muscle are widely recognized, the mechanisms underlying these adaptations are poorly understood and there are currently no widely-accepted clinical interventions to counter them
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, postsurgical 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, the investigators 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. We hypothesize that 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, the investigators posit that NMES will improve functional recovery following TKA by countering these early skeletal muscle adaptations. To test this model, the investigators will evaluate participants with knee OA 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.
Study Type
INTERVENTIONAL
NMES will be conducted on the quadriceps of the operative leg using a portable stimulation device, starting within 48-72 hrs of surgery. The operative leg will be immobilized at a neutral angle (\~30º), with electrodes affixed to the anterior surface of the thigh. Symmetrical, biphasic pulses (400 µs duration at 50 Hz) will be used, with a duty cycle of 25% (10 s on, 30 s off), with patient-selected stimulation intensity to cause visible contractions below pain threshold. NMES sessions will occur 5 d/week, twice daily for 45 min (5 min warm-up) for 5 wks.
University of Vermont College of Medicine
Burlington, Vermont, United States
Cross-sectional Area (CSA) of Muscle Fibers
CSA of skeletal muscle fibers via myosin heavy chain (MHC) immunohistochemistry
Time frame: Baseline and 5-weeks post-TKA surgery
Intermyofibrillar Mitochondrial Content
Fractional area of intermyofibrillar (IMF) mitochondria via electron microscopy
Time frame: Baseline and 5-weeks post-TKA surgery
Maximal Calcium-activated Tension Single Muscle Fiber Tension
Tension (force per unit muscle fiber cross-sectional area) from segments of chemically-skinned single human muscle fibers assessed under maximal calcium-activated condition, with muscle fiber type determined post-measurement by gel electrophoresis
Time frame: Baseline and 5-weeks post-TKA surgery
Physical Activity Level
Physical activity will be assessed by accelerometry.
Time frame: Baseline and 5-weeks post-TKA surgery
Quadriceps Muscle Cross-sectional Area
Quadriceps muscle cross-sectional area will be assessed by computed tomography at the mid-thigh on both surgical and non-surgical non-surgical legs.
Time frame: Baseline and 5-weeks post-TKA surgery
Short Physical Performance Battery
Physical functional assessment based on 2 lower extremity activities (5-time sit-to-stand, 4-m gait speed) and standing balance (side-side, tandem, semi-tandem) based on time or repetitions (0-4 score) with a minimum score of 0 and a maximal score of 12. Each activity is scored from 0 to 4 based on the level of performance (with higher values indicating better physical function and lower values indicating increasing levels of disability). The scores from the 3 activities are summed to give the total score, which is what is reported. Higher total score values indicate higher levels of physical function (more healthy), whereas lower values indicate increasing levels of physical disability/frailty.
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Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
23
Time frame: Baseline and 5-weeks post-TKA surgery
Knee Extensor Muscle Strength
Knee extensor isometric peak torque assessed by dynamometry on the surgical leg.
Time frame: Baseline and 5-weeks post-TKA surgery
30-second Sit-to-stand Test
Number of repetitions that an individual can complete the sit-to-stand transition in 30 seconds
Time frame: Assessed at baseline and 5 weeks post-surgery