Clinical Efficacy of Tissue-Bone Homeostasis Manipulation on Soft Tissue Balance and Function in Knee Osteoarthritis

Summary

Here, we present a protocol to apply tissue-bone homeostasis manipulation for knee osteoarthritis and to evaluate its effects on peripatellar soft tissue tension, knee motion, and functional outcomes.

Abstract

Knee osteoarthritis (KOA) is characterized by progressive joint degeneration and biomechanical imbalance of periarticular soft tissues, leading to pain and functional limitation. However, effective biomechanically targeted manual therapy protocols for regulating soft tissue tension remain insufficiently standardized.

In this study, a randomized controlled design was used to investigate the effects of tissue-bone homeostasis manipulation (TBHM) on peri-knee soft tissue tension and functional outcomes in patients with KOA. Sixty patients were enrolled and randomly assigned to the TBHM group or the control group. Primary outcomes included rectus femoris, vastus medialis, vastus lateralis muscle tension, patellar ligament tension, and knee flexion range of motion (ROM). Secondary outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Timed Up and Go Test (TUGT).

The results showed that baseline characteristics were comparable between groups (all P > 0.05), and no adverse events were observed during the intervention. Repeated measures analysis revealed significant time effects for all primary and secondary outcomes (P < 0.001). Significant group × time interaction effects were observed for rectus femoris, vastus lateralis muscle tension, patellar ligament tension, knee flexion ROM, KOOS subscales (symptoms, activities of daily living, sport/recreation, and quality of life), and TUGT (P < 0.05), indicating greater improvement in the TBHM group compared with the control group. However, no significant interaction effect was found for vastus medialis muscle tension or KOOS-pain (P > 0.05), suggesting similar trends between groups in these measures.

In conclusion, TBHM demonstrates both safety and efficacy in reducing periarticular soft tissue tension and improving functional outcomes in KOA. This protocol provides a standardized and biomechanically oriented approach for manual therapy intervention and may offer a novel strategy for optimizing conservative treatment of KOA.

Introduction

Knee osteoarthritis (KOA) is a highly prevalent degenerative joint disorder in the aging population, characterized not only by progressive cartilage degeneration and osteophyte formation within the knee joint, but also by biomechanical imbalance of periarticular soft tissues, including muscles, ligaments, and fascia, which play a critical role in disease initiation and progression¹. Increasing evidence indicates that abnormal tension in the quadriceps muscle may alter patellar tracking patterns, leading to aberrant stress distribution within the patellofemoral joint and accelerating joint degeneration^2,3. Clinically, KOA presents with insidious onset and progressive symptoms such as pain, swelling, limited mobility, and crepitus, and in advanced stages may result in muscle atrophy, joint deformity, and functional disability, significantly impairing quality of life⁴.

Current stepwise therapeutic strategies, including exercise therapy, nonsteroidal anti-inflammatory drugs, and joint replacement, primarily target symptom relief rather than the underlying biomechanical dysfunction⁵. In particular, early-stage KOA remains challenging due to an incomplete understanding of its biomechanical pathogenesis and the lack of objective, mechanism-oriented evaluation systems. Emerging clinical evidence suggests that patients with KOA commonly present peripatellar myofascial hypertonicity⁶. This abnormal tension state not only contributes to increased stress concentration within the patellofemoral joint⁷, but may also be associated with nociceptive sensitization, leading to anterior knee pain.

Traditional Chinese medicine (TCM)-based manual therapies have been increasingly recognized for their role in regulating local inflammation and restoring joint biomechanical balance. Standardized manipulation techniques have been shown to relieve pain, improve joint stability, and demonstrate favorable safety profiles⁸. However, most existing studies focus primarily on muscle strength parameters of the quadriceps femoris⁹, while the dynamic regulation of soft tissue tension and its mechanistic relationship with patellar mobility remain insufficiently understood¹⁰. Moreover, current evaluation of manual therapy efficacy relies heavily on subjective clinical outcomes, with a lack of objective biomechanical indicators to quantify treatment effects.

Here, we present a protocol for tissue-bone homeostasis manipulation (TBHM) to systematically regulate peripatellar soft-tissue tension and restore patellar mobility in patients with KOA. The overall goal of this method is to provide a standardized, reproducible manual intervention approach and an integrated biomechanical evaluation framework to assess treatment efficacy. Compared with conventional manual therapies that primarily target symptom relief, this protocol emphasizes coordinated regulation of soft-tissue tension and joint kinematics, thereby offering a mechanistically informed intervention strategy. Within the broader context of KOA research, this method bridges the gap between clinical manual therapy and quantitative biomechanical assessment.

This protocol is particularly suitable for patients with KOA who present with peripatellar soft-tissue imbalance, reduced patellar mobility, and functional limitations. It may also be applied in clinical and translational studies aiming to investigate the biomechanical mechanisms of manual therapy or to establish objective outcome measures for rehabilitation interventions.

Protocol

This single-blind randomized controlled trial was conducted at the Rehabilitation Center of the First Affiliated Hospital of Anhui University of Chinese Medicine. The study protocol was approved by the Institutional Ethics Committee (Ref. No: 2024AH-36) and prospectively registered in the Chinese Clinical Trial Registry (ChiCTR2400090977, registered on October 17, 2024). All procedures were performed in accordance with institutional ethical guidelines. The trial was designed and reported in compliance with the Consolidated Standards of Reporting Trials (CONSORT) statement. Ensure that all procedures involving human participants comply with the institutional human research ethics committee guidelines and the Declaration of Helsinki. Obtain written informed consent from all participants before initiating the protocol.

1. Patient recruitment

1. Estimate the sample size using G*Power software (version 3.1.9.7) based on a two-sample independent t-test. Set the effect size to 1.01 and the statistical power to 0.90. Calculate a minimum of 44 participants for two groups. Increase the sample size by 20% to account for potential dropouts, resulting in at least 28 participants per group.
2. Recruit patients diagnosed with knee osteoarthritis (KOA). Screen the patients, check whether they meet the eligibility criteria, and agree to participate.
   NOTE: Patients were recruited from October 17, 2024, to December 30, 2025, at the Rehabilitation Center. Of 70 patients, 65 met eligibility criteria, and 60 agreed to participate in the study. Figure 1 presents the participant flow according to the CONSORT diagram.
3. Obtain written informed consent from all participants prior to enrollment, following ethical approval procedures.
4. Establish the diagnosis of KOA based on medical history, radiographic findings (X-ray), and physical examination performed by experienced orthopedic clinicians.
5. Inclusion criteria
   1. Include participants who meet all of the following conditions:
      1. Include patients who meet the clinical diagnostic criteria for KOA¹¹.
      2. Include patients aged between 40 and 80 years.
      3. Include patients who have Kellgren–Lawrence (K–L) grade II–III on radiographic assessment.
      4. Include patients who have not received any related treatment within 1 month prior to enrollment.
6. Exclusion criteria
   1. Exclude participants who meet any of the following conditions:
      1. Exclude patients who have other rheumatic diseases or severe systemic diseases.
      2. Exclude patients who have a history of knee surgery.

2. Randomization and allocation concealment

1. Generate a random allocation sequence using a computer-based randomization method. Seal the allocation sequence in opaque envelopes to ensure concealment.
2. Assign eligible participants to groups according to the random sequence. Ensure that the intervention is performed by the same therapist to maintain consistency.
3. Blind outcome assessors to group allocation. Ensure that assessors do not participate in treatment procedures.
4. Conduct outcome assessments at baseline and after 6 weeks of intervention.
5. Intervention procedures
   1. Joint mobilization group
      1. Position the patient in a supine position with the knee slightly flexed and relaxed at the edge of the treatment table.
      2. Apply long-axis traction at the ankle joint using both hands. Maintain traction for 15 s and repeat 5 times at grade III–IV intensity.
      3. Perform anterior-posterior gliding. Stabilize the affected limb at the maximal restricted flexion position. Place both thumbs on the anterior proximal tibia and apply posterior-directed force using body weight (15 s × 5 repetitions, grade III–IV).
      4. Perform posterior-anterior gliding. Place the thumbs on the anterior tibia and support the popliteal fossa with the fingers. Apply anterior-directed force (15 s × 5 repetitions, grade III–IV).
      5. Perform anterior tibial glide during hip–knee flexion in the supine position (15 s × 5 repetitions, grade III–IV).
      6. Repeat the above procedures once weekly for 6 consecutive weeks.

3. TBHM group

1. Soft tissue manipulation
   1. Position the patient in a supine position with the lower limb fully exposed and relaxed.
   2. Place the palm or thenar eminence over the anterior thigh muscles. Apply longitudinal pushing along the muscle fibers from proximal to distal using forearm-driven force.
   3. Perform circular kneading using the palm and fingers over the anterior, medial, and lateral thigh muscles, followed by the calf muscles. Maintain continuous contact and moderate pressure (Figure 2).
   4. Continue the manipulation for approximately 3 min.
      NOTE: Ensure that the pressure is sufficient to mobilize soft tissue but does not induce sharp pain. Adjust the intensity based on patient feedback.
2. Pain-point manipulation
   1. Palpate the peri-knee region systematically to identify tender points, including the patellar ligament, synovium, infrapatellar fat pad, muscle insertion sites, and collateral ligaments.
   2. Place the thumb pad or fingertip directly on each identified pain point.
   3. Apply circular kneading using small-amplitude movements in a clockwise or counterclockwise direction around the patella.
   4. Maintain a steady rhythm (approximately 1–2 Hz) with moderate pressure (Figure 3).
   5. Treat each point sequentially for three cycles, with a total duration of approximately 3 min.
   6. Apply focused fingertip kneading to the most sensitive points for an additional 1–2 min.
      NOTE: If pain points are difficult to localize, gradually increase palpation pressure and expand the examination area.
3. Posterior chain relaxation
   1. Reposition the patient in the prone position.
   2. Place both palms over the lumbar region and apply kneading to the erector spinae using rhythmic pressure generated from the forearm.
   3. Progress distally to the gluteal muscles, hamstrings, and triceps surae (Figure 4).
   4. Perform manipulation sequentially from proximal to distal regions.
   5. Maintain moderate and continuous pressure throughout the manipulation.
   6. Repeat three cycles for a total duration of approximately 5 min.
      NOTE: For patients with poor tolerance to the prone position, reduce the duration or perform partial posterior chain release.
4. Patella manipulation
   1. Point kneading of the patella
      1. Position the patient in a relaxed supine position.
      2. Place the thumb pads along the patellar margin.
      3. Divide the patella into two layers: superficial layer (patellar edge) and deep layer (subpatellar structures) (Figure 5).
      4. Apply kneading in eight directions: superior, superomedial, medial, inferomedial, inferior, inferolateral, lateral, and superolateral.
      5. Generate force using small circular thumb movements while maintaining consistent amplitude.
      6. Maintain each direction for 15 s.
      7. Complete all directions in the superficial layer before proceeding to the deep layer.
      8. Progress from superficial to deep layers.
      9. Complete the procedure within approximately 5 min.
         NOTE: Avoid abrupt force application. Maintain smooth and controlled pressure to prevent patient discomfort.
   2. Patella pushing manipulation
      1. Position the patient in a supine position.
      2. Place one thumb on the lateral side of the patella and the fingers on the medial side.
      3. Reinforce the pushing thumb using the opposite palm.
      4. Apply a slow and controlled push-pull movement to the patella in four directions, reaching the maximal tolerable range of motion (Figure 6).
      5. Hold the end position for approximately 3 s.
      6. Gently mobilize the patella along the femoral cartilage surface.
      7. Define one push-pull movement as one cycle (approximately 5 s).
      8. Perform the manipulation for approximately 2 min.
         NOTE: Reduce the amplitude of movement in patients with high pain sensitivity.
5. Exercise-based manipulation
   1. Passive knee flexion-extension
      1. Position the patient in the prone position.
      2. Hold the ankle joint with one hand and stabilize the knee joint with the other.
      3. Perform passive knee extension followed by flexion within the functional range.
      4. Use slow and controlled movements throughout the procedure.
      5. Avoid excessive compression at the end range.
      6. Repeat 5 times within approximately 1 min.
         NOTE: Stop the movement if the patient reports sharp pain.
   2. Traction and shaking
      1. Maintain the knee at approximately 90° flexion in the prone position.
      2. Grasp the ankle with both hands.
      3. Lift the lower leg approximately 10 cm off the treatment bed.
      4. Apply gentle traction combined with rhythmic vertical oscillations.
      5. Maintain a smooth and continuous movement pattern (Figure 7).
      6. Repeat 3 cycles within approximately 1 min.
         NOTE: Ensure that oscillations are small in amplitude to avoid joint irritation.
6. Treatment frequency
   1. Perform the TBHM intervention twice per week.
   2. Continue the treatment for 6 consecutive weeks.
      NOTE: Perform all assessments at baseline, immediately after the 6-week intervention period, and again at the 8-week follow-up. Ensure that outcome assessors are blinded to group allocation and independent from the intervention team.

4. Outcome measures

1. Primary outcomes
   1. Soft tissue tension
      1. Use the soft tissue tension testing system.
      2. Apply a standardized loading force of 500 g.
      3. Record displacement values (mm) to reflect tissue stiffness.
      4. Measure the following sites:
         Rectus femoris (2/3 between ASIS and patella)
         Vastus medialis and vastus lateralis (muscle belly peak)
         Patellar ligament (midpoint between patella and tibial tuberosity)
      5. Repeat measurements three times and calculate the mean value.
   2. Knee flexion range of motion (ROM)
      1. Measure knee flexion ROM using an electronic goniometer.
      2. Position the patient in a prone position.
      3. Place the center (axis) of the goniometer over the lateral femoral condyle.
      4. Align the stationary arm parallel to the longitudinal axis of the femur and the movable arm parallel to the longitudinal axis of the tibia.
      5. Instruct the patient to actively flex the knee to the maximal range.
      6. Record the measurement three times and calculate the mean value for analysis.
2. Secondary outcomes
   1. Timed Up and Go Test (TUGT)
      1. Instruct the patient to sit in a chair with armrests, with the back supported and hands resting on the armrests.
      2. Ask the patient to stand up upon command.
      3. Walk forward for 3 m at a comfortable pace.
      4. Turn around, walk back to the chair, and sit down.
      5. Record the total time required to complete the task.
      6. Repeat the test three times and calculate the mean value.
         NOTE: A shorter completion time indicates better functional mobility
   2. Knee function
      1. Assess knee function using the Knee Injury and Osteoarthritis Outcome Score (KOOS).
      2. Evaluate five domains: pain, symptoms, activities of daily living (ADL), sport and recreation, and quality of life (QoL).
      3. Score each item on a 0–4 scale.
      4. Calculate each subscale score independently.
      5. Convert each subscale score to a normalized 0–100 scale.
         ​NOTE: Higher scores indicate better knee function.

5. Statistical analysis

1. Perform all statistical analyses according to the intention-to-treat principle using the full analysis set. Import all data into statistical software and check for missing values prior to analysis.
2. Test the normality of continuous variables using the Shapiro–Wilk test. Analyze normally distributed variables using one-way analysis of variance (ANOVA), and analyze non-normally distributed variables using the Kruskal-Wallis test.
3. Analyze categorical variables using the chi-square test. Perform two-way repeated measures ANOVA to evaluate the interaction between group (TBHM group vs. control group) and time (baseline, post-intervention, and follow-up).
4. Set the significance level at P < 0.05. Conduct post hoc simple effects analysis for variables with significant interaction effects. Perform all analyses using statistical software.

Results

Baseline characteristics of patients
Table 1 summarizes the demographic and clinical baseline characteristics of the 60 enrolled patients. Comparative analysis revealed homogeneity between the two groups, with no statistically significant differences in age, gender, anthropometric measures (weight, height, BMI), disease chronicity, laterality of affected limbs, radiological parameters (K-L grade) (all P > 0.05). Critically, the intervention demonstrated a favorable safety...

Discussion

This study demonstrated that a 6-week TBHM protocol can effectively reduce peripatellar soft tissue tension and improve functional outcomes in patients with KOA, without inducing obvious adverse events. Compared with conventional joint mobilization, TBHM produced greater reductions in rectus femoris, vastus lateralis, and patellar ligament tension, accompanied by improvements in knee flexion ROM, KOOS scores, and TUGT performance. These findings indicate that the protocol is safe, feasible, and clinically applicable for ...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Electronic goniometer	Shengtai Xinyi Electronic Technology Co., Ltd. of Deqing	GJJDC01	Used to measure knee flexion range of motion (ROM) with alignment along the femur and tibia axes.
Soft tissue tension testing system	Tianjin Mingtong Century Technology Co., Ltd.	JZL-III	Used to quantify soft tissue mechanical properties by measuring tissue displacement under a standardized loading force (500 g).
Stopwatch	Shenzhen Yisheng Technology Co., Ltd.	YS-528	Used to record time-based functional performance during the Timed Up and Go Test.