This was a prospective, single-center, parallel-group, randomized controlled trial. A total of 101 patients with end-stage knee OA scheduled for primary TKA were enrolled in this prospective study between February 2018 and February 2019. The exclusion criteria were as follows: a history of serious peripheral circulatory disturbances, heart or respiratory problems, central or peripheral neurological disorders, and dementia. Patients with spinal disease complications or lower-extremity symptoms were also excluded. Finally, 76 patients were included in the analysis (Fig. 1). All the patients provided written informed consent to participate in the study. This study was conducted in accordance with the Declaration of Helsinki and was approved by the Hirosaki Memorial Hospital Research Ethics Committee (H29-14). This study was registered to UMIN-CTR on 01/09/2023 (Trial Registration Number: UMIN000052086).
Randomization and blinding
Participants who met the eligibility criteria were randomly assigned to (1) knee extension exercise using HAL-SJ combined with CPT (HAL-SJ group) or (2) CPT including knee extension exercise without HAL-SJ (CPT: CPT group). Independent of the study, the therapist created a random number table and assigned participants who met the eligibility criteria to the order in which they were admitted. The therapist was informed only of the patient’s ID and was blinded to the baseline evaluation. All participants and their physical therapists were informed of the assigned groups on the day after TKA.
Conventional physical therapy
All participants in the HAL-SJ and CPT groups underwent CPT. Physical therapy after TKA started on postoperative day 1. The rehabilitation program was as follows: active and passive knee ROM exercises, quadriceps muscle strength exercises, gait exercises performed on postoperative day 3, and stair-climbing exercises performed on postoperative day 8. All rehabilitation programs were managed by a physical therapist with careful monitoring of the worsening of the pain. Physical therapy was continued until discharge from the hospital at a frequency of five times a week. Participants in the CPT group started active knee extension exercises on postoperative day 4, in addition to the above-mentioned physical therapy. Participants began the exercise in a sitting position, extending the knee joint as much as possible and then flexing it back to the initial knee joint position. During the active knee extension exercises, the physical therapist did not assist with knee joint movement but only provided verbal instructions. These exercises counted as a one-time exercise and were performed 50 times a day. These active knee extension exercises were performed for five sessions per week, and the total number of sessions was 10 (i.e., 10 sessions in 2 weeks).
The patients in the HAL-SJ group performed knee extension exercises in combination with CPT. The HAL-SJ was composed of a power unit, thigh and lower leg attachments, a control device, and a lithium-ion battery (Fig. 2a). The HAL-SJ can perceive bioelectrical signals from the knee extensor or flexor muscles and assist in knee motion according to these signals7,9. The electrodes used to perceive bioelectrical signals were set on the skin of the front and rear thighs (Fig. 2b). The HAL-SJ provided visual feedback through the control device via the LED ring positioned on the side of the power unit using various colors according to the bioelectrical signal. Similar to the CPT group, participants began the exercise in a seated position. In the knee extension exercise, the HAL-SJ assisted the knee joint movement according to voluntary muscle activity, and a physical therapist did not assist the joint movement. With the assistance of the HAL-SJ, participants extended the knee joint as far as possible and then flexed the knee joint to return it to the initial knee joint position. The physical therapist immediately informed the participants whether muscle activation during the knee extension exercise was correct. In this study, incorrect muscle activation was defined as knee flexor activation during knee extension and knee extensor activation during knee flexion. The physical therapist adjusted the amount of assistance from the HAL-SJ to achieve full knee extension in each patient. The active knee extension exercises using the HAL-SJ were performed 50 times per day, five sessions per week, as in the CPT group; therefore, the total number of sessions was 10. The number of trials per day was determined based on the report of Goto et al.8. The frequency and total number of exercise sessions in exploratory studies were more frequent than those in previous studies. Physical therapy and interventions in the CPT and HAL-SJ groups are described in Supplemental Table S1.
Cruciate-substitute (CS) type TKAs using the Triathlon Knee CS System (Stryker Japan K.K., Tokyo) were performed with the measured resection technique without a navigation system. These surgeries were performed by three senior joint surgeons (ES, YW, and TS). A medial parapatellar approach was used to expose the knees. A femoral osteotomy was performed using an intramedullary guide. A tibial osteotomy was performed using an extramedullary guide with a varus/valgus angle of 0° and a slightly posterior slope. The gap was measured using a tensor. The soft tissue balance was adjusted for straight alignment with minimized medial soft tissue release in a step-by-step manner, such that the medial and lateral gap differences were less than 3 mm at both full extension and 90° flexion. Finally, the components were implanted using a cementless technique.
The main outcomes measured in the present study were pain intensity during knee motion and active and passive knee extension angles. Isometric knee extension strength (IKES), gait, standing and sitting abilities, ADL, and QOL were assessed as ancillary outcome measures.
Pain intensity during active knee motion was evaluated using a visual analogue scale (VAS). The VAS is a 100-mm-long horizontal line anchored by word descriptors at each end. The left side of the scale (0 mm) reads “no pain,” and the right side of the scale (100 mm) reads “worst pain imaginable.” Each participant drew a vertical mark on the line at the point that best represented their perceived pain.
Active and passive knee extension angles
The participants were seated on a bed, and two sagittal plane photographs of each active and passive knee extension were obtained. The knee extension angle was measured using image analysis software (ImageJ; National Institutes of Health, Bethesda, MD, United States)10. The knee extension angle analysis was performed by two physical therapists who were blinded to the group assignments. The average value was used for statistical analysis.
Participants were seated in a wheelchair with their hip and knee joints flexed and stabilized at 90°. A handheld dynamometer (Microfet2; HOGGAN Scientific, Salt Lake City, UT, United States) was fixed at one-third of the distal part of each participant’s lower leg. The evaluator asked the participants to extend their knees maximally for 3 s. All evaluations were performed by the same evaluator. The intraclass correlation coefficient (ICC) was calculated before this study. ICC (1,1) was 0.94 (95% confidence interval [CI] 0.64–0.99), and ICC (1,2) was 0.97 (95% CI 0.78–0.99). To obtain sufficient reliability, the evaluation was performed twice at each time point, and the larger value was used for comparison.
Gait ability was evaluated using the 10-m maximal walking test (MWT). The patient walked 10 m as quickly as possible. The patient was allowed to use assistive and/or orthotic devices if necessary. Two trials were performed, and the shorter time was used to compare and calculate the walking rate (WR).
Timed up and go test (TUG)
The TUG test was used to evaluate standing-up and sitting-down abilities. In this study, the participant was instructed to stand when the evaluator said “start”, walk at a maximal speed past the 3-m mark, turn around, walk back, and sit in the chair. The time required for the TUG test was measured using a stopwatch and recorded to the nearest second. The evaluation time point at each TUG was performed twice, and the faster time was used for statistical analysis.
ADL and QOL
ADL and QOL were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS)11. KOOS is a self-answered questionnaire that consists of five subscales: Pain, Other Disease-Specific Symptoms, ADL Function, Sport and Recreation Function, and Knee-Related QOL. A previous study showed that KOOS is an appropriate outcome measure in patients after TKA12. However, patients with severe knee OA often skipped answering the item on sports in the KOOS as it was considered irrelevant to their daily lives13. In this study, because the participants did not perform the motion presented in the KOOS (i.e., running and jumping) 4 weeks after TKA, this study excluded the subscale of sports in the KOOS for statistical analysis.
The pain intensity and active and passive knee extension angles were evaluated for 10 days before and after each intervention. Additionally, pain intensity, active and passive knee extension angles, IKES, MWT, and TUG were evaluated periodically before surgery and 2 and 4 weeks after TKA. The KOOS score was evaluated before and 4 weeks after TKA.
The sample size was calculated using G-power before the study, with an alpha of 0.05, a power of 0.80, and an effect size of 0.25. The analysis of variance (ANOVA) calculation for the split-plot factorial design showed that a total of 44 patients were needed in each group, and 36 patients were needed in each group for the paired t-test.
Preoperative data for the HAL-SJ and CPT groups were compared using two-sample t-tests for age and body mass index and Pearson’s chi-square test for the ratio of women. The amount of change in pain intensity and active and passive knee extension angles before and after intervention for 10 days in each group was calculated. Mendoza’s multisample sphericity test was performed; split-plot ANOVA was performed when sphericity was assumed; and split-plot ANOVA with Greenhouse–Geisser’s epsilon correction was performed when sphericity was not assumed. The ANOVA was used to compare the number of changes over 10 days and periodic evaluations (i.e., before TKA and 2 and 4 weeks after TKA) of the HAL-SJ and CPT groups. If the interaction was significant, a two-sample t-test was used to compare the group differences at each evaluation point. A post hoc test using the Shaffer method was performed when only the main effect of the repeated-measures factor was significant. In addition, to investigate the immediate effect of the intervention, pain intensity and active and passive knee extension angles before and after intervention in each group for 10 days were compared using a paired t-test with the Bonferroni correction.
The threshold for significance was set at p = 0.05. All statistical analyses were performed using R version 3.6.3(R: R Foundation for Statistical Computing, Vienna, Austria).