The Dynamic Dual-Mode Alignment Optimization and Intelligent Precision Knee Preservation System for Knee Osteoarthritis
Phase: NA
Conditions: Knee Osteoarthritis (Knee OA)
Sponsor: First Affiliated Hospital of Wenzhou Medical University

The Dynamic Dual-Mode Alignment Optimization and Intelligent
Precision Knee Preservation System for Knee Osteoarthritis
Research Institution: The First Affiliated Hospital of Wenzhou Medical University
Principal Investigator: Zhang Lei
Responsible Department: Department of Joint Surgery
Contact Number: 13587557573
Collaborating Institutions: Beijing Jishuitan Hospital, Ningbo Sixth People's Hospital
Version No.: 2.0
Version Date: September 3 , 2025

Scheme Abstract
Item
Content
Project Name:
The
Dynamic
Dual-Mode
Alignment
Optimization
and
IntelligentPrecision
Knee
Preservation System for Knee Osteoarthritis
Research Objectives：
1. Clinical comparative study of neutral alignment vs. traditional alignment for knee
preservation (completed); 2. Clinical comparative treatment of kinematic alignment vs. traditional
alignment for knee preservation; 3. Clinical comparative study of 3D-printed guide plate-guided
HTO vs. traditional surgery; 4. Optimization of preoperative surgical planning strategy based on
CT imaging and verification of the accuracy of corresponding 3D-printed guide plates; 5.
Accuracy verification of AR real-time feedback in intraoperative alignment adjustment for HTO
Study Subjects：Patients with knee osteoarthritis (KOA) requiring high tibial osteotomy (HTO)
(K-L grade Ⅱ-Ⅲ)
Sample Size: Total: 120 cases (3 groups, 40 cases per group)
Inclusion Criteria:
1. Aged 40-70 years; 2. Unilateral medial compartment knee osteoarthritis (mild to moderate
pain); 3. Mild to moderate varus deformity (5°-15°); 4. Coronal MRI shows medial meniscus
extrusion (MME) > 3 mm, flexion contracture < 10°; 5. Intact lateral meniscus and cartilage; 6.
Voluntarily sign informed consent
Exclusion Criteria:
1. Complicated with inflammatory arthritis (e.g., rheumatoid arthritis) or systemic
inflammatory diseases; 2. Severe varus deformity (>10°) or flexion contracture >10°; 3. Lateral
meniscus lesions (tear, discoid meniscus) or knee instability; 4. History of major knee
trauma/infection/previous surgery; 5. Severe patellofemoral arthritis; 6. Advanced medial
compartment osteoarthritis (bone-on-bone contact or knee subluxation); 7. Refusal of secondary
arthroscopic review or study participation; 8. Failure to complete at least 12 months of follow-up;
9. Severe osteoporosis; 10. Cognitive impairment
Study Design:
This study adopts a prospective, multicenter, multi-module mixed design, combining

randomized controlled trial (RCT), prospective cohort study, and self-controlled study to
systematically evaluate the effectiveness, accuracy, and clinical value of dynamic dual-mode
alignment optimization (neutral position + kinematic alignment) and intelligent precision
knee-preserving system (3D-printed guide plate, AR navigation).
1.
Kinematic Alignment (KA) vs. Traditional Mechanical Alignment (MA) for Knee
Preservation: Multicenter, assessor-blinded, three-arm parallel-group RCT. Group 1 (MA
group): HTO guided by traditional mechanical axis alignment; Group 2 (KA group): HTO
guided by personalized kinematic alignment based on dynamic knee kinematic assessment;
Group 3 (DA group - Dynamic Dual-mode Alignment group): HTO guided by dynamic
dual-mode alignment combining neutral alignment and KA.
2.
3D-Printed Guide Plate-Guided HTO vs. Traditional HTO: Multicenter, assessor-blinded
RCT. Group A (Traditional group): Traditional manual HTO based on intraoperative
fluoroscopy and empirical judgment; Group B (3D Guide Plate group): HTO based on
optimized preoperative CT planning and 3D-printed osteotomy guide plate.
3.
Optimization of CT-Based Preoperative Planning and Accuracy Verification of 3D-Printed
Guide Plates:
Prospective
cohort
study. Method: Preoperative
virtual
planning vs.
postoperative actual results - 3D registration of postoperative CT data with preoperative
planning data to quantitatively measure differences in key parameters (coronal MPTA angle,
sagittal PTA angle, osteotomy depth, angle, osteotomy surface position, and deviation
between planned and actual guide plate placement).
4.
Accuracy Verification of AR Real-Time Feedback in Intraoperative HTO Alignment
Adjustment: Prospective cohort study (self-controlled). Verification process: Step 1 (Routine
Adjustment): Surgeon performs initial alignment adjustment and temporary fixation based on
experience, fluoroscopy, and/or 3D guide plate (if used); Step 2 (AR-Guided Adjustment):
Turn on AR navigation system, surgeon performs fine adjustment under AR real-time
visualization feedback (showing deviation between current and target alignment); Step 3
(Final Confirmation): Confirm final alignment using standard fluoroscopy (full-length film).
Outcome Measures:
1.
Alignment Comparison: Primary endpoint - 1-year postoperative WOMAC total score; Key
secondary endpoints - 2-year postoperative KOOS score, VAS pain score, gait parameters,

reoperation rate.
2.
Guide Plate vs. Traditional: Primary endpoint - Postoperative HKA planned-actual difference;
Secondary endpoints - Operation time, fluoroscopy times, 6-week postoperative ROM,
complication rate.
3.
Guide Plate Accuracy: Primary endpoint - 3D registration error (MPTA/PPTA angle
difference); Secondary endpoints - Osteotomy depth deviation (mm), guide plate clinical
usability score.
4.
AR Verification: Primary endpoint - Change in alignment deviation (HKA angle) before and
after AR adjustment; Secondary endpoints - AR adjustment time, surgeon satisfaction score,
system registration error.
Statistical Analysis:
A stratified statistical analysis framework will be adopted: For intergroup comparisons,
continuous primary endpoints (WOMAC total score, MPTA angle difference) will use analysis of
covariance to adjust baseline values; Kruskal-Wallis H test will be used for heterogeneous
variance. Categorical variables (complication rate) will use chi-square test or Fisher's exact test,
with Bonferroni correction for multiple comparisons among three groups. Repeated measurement
data (multi-timepoint VAS/KOOS/ROM) will use linear mixed-effects model (LMM) to analyze
time effect, intergroup effect, and interaction, with random intercept to control individual
differences. For accuracy verification, paired t-test or Wilcoxon signed-rank test will compare
systematic deviation between preoperative planning and postoperative measurement values;
Bland-Altman consistency analysis will calculate 95% limits of agreement (LoA) and intraclass
correlation coefficient (ICC) to evaluate measurement reliability. Correlation analysis will use
Pearson/Spearman correlation coefficients to explore the association between alignment accuracy
and clinical outcomes. All analyses will be based on the intention-to-treat (ITT) principle; missing
data will use multiple imputation for sensitivity analysis. Two-tailed α=0.05 will be set as the
significance threshold, using SPSS 26.0 and R 4.3.1 software.
Study Duration:
September 2026 - August 2028 (24 months)

1. Research Background
1.1 Clinical Problems to Be Solved and Necessity
Knee Osteoarthritis (KOA) is one of the major diseases with a rising global disability burden,
especially medial unicompartmental OA combined with mechanical varus alignment, which has a
significant incidence in middle-aged and elderly populations as well as young and middle-aged people
with high sports demands. Its pathogenesis is closely related to lower limb alignment abnormalities:
medial deviation of the mechanical axis leads to long-term excessive load on the medial compartment,
accelerating cartilage degeneration and meniscal injury. High Tibial Osteotomy (HTO), as an important
strategy for current knee-preserving treatment, aims to accurately adjust the overall alignment of the
lower limb, transferring weight-bearing from the diseased medial compartment to the relatively healthy
lateral compartment, thereby reducing mechanical stress in the lesioned area, delaying the degenerative
process, and improving pain and function. This remodeling of the mechanical environment is clinically
referred to as "joint restart," creating a biomechanical premise for cartilage repair and joint function
recovery.
However, current mainstream preoperative planning for HTO mostly adopts a "one-size-fits-all"
strategy based on static mechanical axis targets (e.g., Fujisawa point, approximately 62% of tibial
plateau width), with multiple limitations:

Neglect of individual differences: Significant differences exist in anatomical structure, soft tissue
tension, meniscus and cartilage status, and gait kinematic patterns among different patients,
making fixed targets unsuitable for all populations;

Risk of overcorrection or undercorrection: Minor errors in the mechanical axis position can lead
to significant changes in medial-lateral force, affecting clinical efficacy and long-term survival
rate;

Inconsistency between static and dynamic loading: Static imaging targets cannot accurately reflect
dynamic load states such as walking and uphill/downhill walking, which may result in 达标on
imaging but unimproved or even worsened function and symptoms;

Limited execution accuracy: Traditional operation methods relying on manual positioning and
intraoperative fluoroscopy are highly dependent on surgeon experience, leading to easy deviation
of key parameters such as HKA, MPTA, and PTS, while increasing radiation exposure and

operation time.
At present, there is a lack of an individualized precision knee-preserving system that can balance
static accuracy and dynamic functional matching and can be widely promoted clinically. Especially in
the context of no consensus on the "optimal target alignment," how to integrate static alignment
(neutral or mild valgus) with dynamic functional indicators (e.g., knee adduction moment KAM, varus
thrust), and realize a closed-loop of planning-execution-verification through digital means such as CT
3D planning, 3D-printed patient-specific instrumentation (PSI), and intraoperative augmented reality
(AR) real-time feedback, has become an urgent clinical problem to be solved.
This study intends to construct and systematically verify a dual-mode alignment strategy of "static
neutral target + dynamic functional target," combined with AI-assisted CT planning, 3D-printed PSI
execution, and intraoperative AR fine adjustment, to achieve truly individualized precision orthopedics.
Through rigorous verification from multiple dimensions such as kinematics, imaging, patient-reported
outcomes (PROs), safety, and economics, it will provide high-quality evidence-based basis for clinical
practice and promote KOA knee-preserving treatment to enter a new stage of functionalization and
precision.
1.2 Epidemiology/Clinical/Instrument/Background
Knee Osteoarthritis (KOA) is one of the most common disabling musculoskeletal diseases
worldwide. According to the Global Burden of Disease Study, the age-standardized prevalence of KOA
worldwide was approximately 5.5%-7.1% in 2020, with a total of over 650 million patients; its
prevalence has increased by more than 9% since 1990, and disability-adjusted life years (DALY) has
increased by approximately 9.5%. Epidemiological surveys in China show that the total prevalence of
KOA in people aged ≥40 years is 8.1%, with higher prevalence in women than men, and it increases
significantly with age; in people aged ≥60 years, the prevalence can exceed 20%. With aging and
obesity epidemics, the number of KOA patients is expected to continue to rise in the next 20 years,
bringing a huge burden to the social labor force and medical system.
Total Knee Arthroplasty (TKA) can effectively relieve advanced symptoms, but the 10-year
revision rate in young patients is significantly higher than that in the elderly, and revision surgery is
complex and costly. Therefore, "delaying replacement and preserving joints" has important public
health significance in this patient population. As the core surgical method for knee-preserving treatment,

High Tibial Osteotomy (HTO) has multiple advantages: it optimizes the lower limb alignment to
reduce the load on the lesioned compartment and delay joint degeneration; unlike joint replacement,
HTO retains the patient's own joint structure and proprioception, maintains the natural movement
trajectory of the knee joint, and helps to better complete advanced functional activities such as
squatting, running, and jumping; some patients can recover exercise ability after surgery and
re-participate in daily exercise or even competitive sports; at the same time, HTO creates more ideal
alignment and soft tissue conditions for patients who may need TKA in the future, thereby extending
the service life of the joint and improving surgical effects.
In knee-preserving surgery, the core of HTO lies in optimizing the joint force environment by
changing the lower limb alignment to delay disease progression. However, the difference between
preoperative planning and intraoperative execution directly determines the accuracy of orthopedics and
long-term efficacy. Although existing planning is mostly based on static mechanical axis targets, in
practical application, alignment strategies need to be more refined and individualized according to the
patient's soft tissue balance, meniscus and cartilage status, and gait kinematic characteristics.
In recent years, the application of digital auxiliary means in HTO has gradually emerged:
(1)
Patient-Specific Instrumentation (PSI) can perform individualized osteotomy planning and guide
plate production based on 3D images, showing high accuracy in coronal alignment (HKA, MPTA)
and sagittal (PTS) control, while reducing intraoperative fluoroscopy times and operation time.
However, its limitations include long production cycle, dependence on high-quality images,
insufficient cross-center consistency, and lack of consistent evidence for its advantages in
long-term functional outcomes and joint survival rate.
(2)
Augmented reality (AR) or mixed reality navigation can provide real-time superimposed display
of alignment and osteotomy information during surgery, realizing dynamic visualization and
precise fine adjustment, which has potential in improving surgical controllability and reducing
repeated fluoroscopy. However, it is currently mostly in the bench or small-sample clinical stage,
with problems such as hardware dependence, affected registration accuracy, and visual field
interference, and its translational value for patients' final functional benefits needs to be verified
by large-scale clinical studies.
In summary, how to integrate individualized functional goals into planning while maintaining
execution accuracy, and establish a digital precision knee-preserving system that can be stably

promoted under multicenter conditions, is the core problem to be solved urgently. The "dual-mode
alignment + digital execution closed-loop" proposed in this study is a systematic solution to the above
shortcomings.
1.3 Existing Evidence and Controversies
1.3.1 Clinical Evidence and Controversies of Target Alignment Strategies
At present, there is no unified consensus on the preoperative target alignment for HTO
internationally. The mild valgus strategy represented by the Fujisawa point (WBL about 62–62.5%) is
widely used, but in recent years, multiple studies have questioned the universality of this "fixed target"
in all populations. Katagiri et al. (2023) reported that there was no significant difference in short-term
clinical outcomes between neutral alignment and centralization strategy in patients with medial
meniscus posterior root tear combined with varus. The prospective randomized controlled study of our
team showed that there was no significant difference in postoperative functional recovery and pain
improvement between neutral position and Fujisawa point target in patients with MMPRT combined
with varus, while neutral position could avoid the risk of overcorrection in some patients. Other
scholars have pointed out that excessive lateral shift of the Fujisawa point may increase lateral
compartment stress and accelerate lateral cartilage degeneration. These results suggest that the optimal
target alignment should consider individual anatomy, soft tissue, and dynamic load characteristics,
rather than a "one-size-fits-all" model.
1.3.2 Accuracy and Limitations of Digital Execution Tools
Patient-specific guide plates (PSI) and computer-assisted surgery (CAS) are considered to
improve the execution accuracy of HTO. Multiple systematic reviews and meta-analyses have
confirmed that PSI is superior to traditional techniques in coronal alignment (HKA, MPTA) and
sagittal (PTS) control, and can reduce intraoperative fluoroscopy time. However, there is no consistent
conclusion on the advantages in long-term functional outcomes and joint survival rate; in addition, the
production cycle, cost of PSI, and dependence on high-quality images limit its wide promotion in
multicenter
settings.
Augmented
reality
(AR)
navigation
can
provide
real-time
visualized
superimposition of alignment and osteotomy information during surgery, helping to fine-tune alignment
and reduce radiation exposure. Chui ECS et al.'s bench and cadaver tests verified the feasibility of
markerless AR navigation, but its accuracy stability and translational value for patient function in large

clinical samples still need further verification.
1.3.3 Correlation between Kinematic Indicators and Clinical Outcomes
Gait studies have shown that peak knee adduction moment (KAM) and its impulse are important
predictors of KOA pain and structural progression (Miyazaki T et al., 2002; Sharma L et al., 2017). At
the same time, the presence of varus thrust is significantly associated with the occurrence and
aggravation of KOA. However, existing HTO studies mostly use static image alignment as the main
efficacy evaluation index, lacking systematic studies that link dynamic load indicators with static
accuracy, functional outcomes, and safety. This leads to incomplete optimization of dynamic load
distribution and symptoms in some patients even if static indicators are met.
1.3.4 Evidence Gaps to Be Addressed by This Study
Based on the above literature review, there is currently a lack of prospective multicenter clinical
studies that combine individualized target alignment strategies with digital precision execution tools
(PSI,
AR)
and
simultaneously
evaluate
from
the
full
chain
of
dynamic
load-static
alignment-patient-reported outcomes-safety. The design of this study is to fill this evidence gap, verify
the real benefits of the "dual-mode alignment + digital closed-loop knee-preserving system" on
multi-dimensional indicators, and provide high-quality evidence-based basis for KOA knee-preserving
treatment.
2. Research Objectives
2.1 Primary Objective
To verify
that
the
"dynamic
dual-mode alignment optimization
+ intelligent
precision
knee-preserving system" (integrating multi-module technologies such as static/kinematic target
alignment, CT-based preoperative 3D planning, 3D-printed guide plate guidance, and intraoperative AR
real-time feedback) can achieve a more significant relative reduction in peak knee adduction moment
(KAM) at 12 months postoperatively compared with traditional knee-preserving strategies, while
maintaining or improving knee clinical function without increasing the incidence of perioperative and
medium-to-long-term complications.
2.2 Secondary Objectives
(1)
Improve static alignment accuracy and sagittal control ability;

(2)
Improve dynamic load parameters such as varus thrust and KAM impulse;
(3)
Improve patient-reported outcomes (PROs) scores and MCID compliance rate;
(4)
Optimize perioperative process, reduce intraoperative radiation exposure and shorten operation
time;
(5)
Verify the safety and cost-effectiveness advantages of the scheme.
2.3 Sub-study Objectives
(1)
Clinical Comparative Study of Neutral Alignment vs. Traditional Alignment for Knee
Preservation (Completed): To compare the differences between the two static target alignments in
KAM improvement and function enhancement, providing a benchmark for subsequent kinematic
optimization.
(2)
Clinical Comparative Treatment of Kinematic Alignment vs. Traditional Alignment for Knee
Preservation: To verify the advantages of kinematic target alignment in reducing dynamic loads
(KAM, varus thrust).
(3)
Clinical Comparative Study of 3D-Printed Guide Plate-Guided HTO vs. Traditional Surgery: To
evaluate the effect of PSI guide plate in improving alignment accuracy, reducing radiation and
operation time.
(4)
Optimization of Preoperative Surgical Planning Strategy Based on CT Imaging and Accuracy
Verification of Corresponding 3D-Printed Guide Plates: To optimize preoperative 3D planning
parameters and verify the accuracy of guide plate production and application.
(5)
Accuracy Verification of AR Real-Time Feedback in Intraoperative HTO Alignment Adjustment:
To compare the differences in intraoperative alignment adjustment accuracy and efficiency
between AR navigation and traditional fluoroscopy.
3. Study Type
This is a prospective, randomized, controlled, partially blinded multicenter clinical study.
3.1 Overall Design Type
(1)
Prospective: All cases preset inclusion criteria and research procedures before surgery, and follow
up according to the established time window after surgery.
(2)
Random Grouping: All sub-studies (except the completed "neutral alignment vs. traditional

alignment for knee preservation" comparative study) adopt computer random number table to
assign subjects to experimental group or control group.
(3)
Control Methods:

Kinematic alignment vs. traditional static alignment;

3D-printed guide plate-guided HTO vs. traditional intraoperative fluoroscopy HTO;

CT planning-optimized guide plate vs. conventional guide plate design;

AR intraoperative real-time feedback vs. traditional fluoroscopy adjustment.
(4)
Blinding: Due to obvious differences in intervention methods, surgeons and patients cannot be
blinded; assessor blinding is adopted (postoperative imaging parameters, gait/kinematic data, and
PROs scores are analyzed by independent assessors unaware of grouping information).
3.2 Sub-study Blinding and Randomization Details
(1)
Kinematic vs. Traditional Alignment: 1:1 randomization; assessor blinding.
(2)
3D-Printed Guide Plate vs. Traditional HTO: 1:1 randomization; imaging and function assessor
blinding.
(3)
CT Planning Optimization vs. Conventional Planning: 1:1 randomization; postoperative imaging
accuracy analysis by blinded measurement.
(4)
AR Feedback vs. Traditional Fluoroscopy: 1:1 randomization; postoperative imaging and function
assessor blinding.
(5)
The completed study (neutral vs. traditional alignment) is a prospective randomized controlled
design, and the results are used as methodological and effect size references, not included in the
current random sequence.
3.3 Summary of Study Characteristics
(1)
Study Type: Clinical interventional trial
(2)
Design Attributes: Prospective, randomized, parallel-controlled, partially blinded, multicenter
(3)
Main Evaluation Time Points: Preoperative baseline, 6 weeks, 3 months, 6 months, 12 months
postoperatively
(4)
Data Analysis Principle: Primary endpoints by intention-to-treat (ITT), safety endpoints by
exposed population

4. Study Subjects and Case Selection
4.1 Inclusion Criteria
(1)
Aged 40-70 years;
(2)
Unilateral medial compartment knee osteoarthritis (mild to moderate pain);
(3)
Mild to moderate varus deformity (5°-15°);
(4)
Coronal MRI shows medial meniscus extrusion (MME) > 3 mm, flexion contracture < 10°;
(5)
Intact lateral meniscus and cartilage;
(6)
Voluntarily sign informed consent.
4.2 Exclusion Criteria
(1)
Complicated with inflammatory arthritis (e.g., rheumatoid arthritis) or systemic inflammatory
diseases;
(2)
Severe varus deformity (>10°) or flexion contracture >10°;
(3)
Lateral meniscus lesions (tear, discoid meniscus) or knee instability;
(4)
History of major knee trauma/infection/previous surgery;
(5)
Severe patellofemoral arthritis;
(6)
Advanced medial compartment osteoarthritis (bone-on-bone contact or knee subluxation);
(7)
Refusal of secondary arthroscopic review or study participation;
(8)
Failure to complete at least 12 months of follow-up;
(9)
Severe osteoporosis;
(10) Cognitive impairment.
5. Study Design
5.1 Intervention Measures
5.1.1 Intervention Group
The intervention group adopts the "dynamic dual-mode alignment optimization + intelligent
precision knee-preserving system," integrating the following elements:
(1)
Preoperative Planning:

Static target alignment: Measure HKA, MPTA, JLCA, etc., based on full-length standing X-ray,
and set orthopedic target (individualized ± neutral position).


Kinematic target alignment: Calculate dual-mode comprehensive target using 3D gait analysis and
ground reaction force data, combined with varus thrust, peak KAM, and KAM impulse.

CT 3D reconstruction and surgical simulation: Acquire full-length femoral and tibial images using
high-resolution CT (slice thickness ≤1mm), reconstruct 3D model, and set osteotomy plane,
wedge opening amount, and hinge position.

3D-printed personalized guide plate (PSI): Design and print according to optimized planning data,
including positioning guide plate and osteotomy guide groove.
(2)
Intraoperative Operation:

AR real-time feedback navigation: Register full-length lower limb images with 3D planning
model during surgery to realize AR real-time superimposed display of alignment changes and
dynamically adjust to planning target.

Osteotomy technique: Single-plane opening wedge HTO (OWHTO) with locking plate fixation.

Alignment confirmation: Recheck alignment and PTS under simulated weight-bearing, adjust
opening amount or hinge position if necessary.
(3)
Postoperative Management:

Lower limb muscle strength training and range of motion (ROM) training from the first day after
surgery;

Partial weight-bearing on the ground 2–3 days after surgery (adjusted according to bone quality
and fixation stability);

Gradual full weight-bearing 3–4 weeks after surgery;

Follow ERAS bundle care process, strengthen pain management and anti-thrombosis measures.
5.1.2 Control Group
The control group adopts traditional knee-preserving strategy, without kinematic alignment,
personalized CT planning, 3D-printed guide plate, and AR real-time feedback. Specific measures are as
follows:
(1)
Preoperative Planning:
Only set traditional static orthopedic target (e.g., postoperative HKA≈183°) based on full-length
standing X-ray, without kinematic evaluation and CT 3D planning.
(2)
Intraoperative Operation:
Adopt traditional open high tibial osteotomy (OWHTO), with osteotomy and opening amount

confirmed by surgeon's experience and intraoperative conventional fluoroscopy; alignment adjustment
based on estimation of mechanical axis under intraoperative fluoroscopy; no 3D-printed guide plate or
AR navigation.
(3)
Postoperative Management:
Implement routine rehabilitation and nursing programs with reference to the intervention group;
consistent pain management and anti-thrombosis programs.
5.1.3 Concomitant Medication and Prohibited Medication Regulations
(1)
Allowed: Routine analgesics (NSAIDs), anticoagulants (low molecular weight heparin or oral
anticoagulants), bone health management drugs (e.g., calcium, vitamin D).
(2)
Prohibited: Long-term systemic glucocorticoids; intra-articular injections outside the study scope
(hyaluronic acid, hormones, etc.); other lower limb surgical interventions that may affect gait
analysis.
All concomitant medications should be recorded and adjusted as covariates in data analysis.
5.2 Study Cycle and Visit Plan
5.2.1 Study Cycle
The total cycle of this study is 24 months, divided into four stages:
(1)
Preparation Stage (Months 0–3): Team formation and training; formulation of SOP, improvement
of case report form (CRF) and electronic data capture system (EDC); completion of ethical
approval and pilot enrollment.
(2)
Enrollment and Intervention Stage (Months 4–18): Allocate intervention group and control group
according to randomization scheme; continuous case enrollment and intervention implementation;
completion of preoperative baseline assessment and early postoperative follow-up.
(3)
Follow-up and Data Collection Stage (Months 18–22): Complete clinical follow-up and testing
according to preset visit points; ensure that the completion rate of 12-month primary endpoint
assessment is ≥90%.
(4)
Data Analysis and Conclusion Stage (Months 22–24): Data cleaning and statistical analysis;
writing research report and paper submission.

5.2.2 Visit Points and Contents
Visit Point
Time Point
Main Contents
V0
Preoperative
(on
enrollment day or
within
1
week
before surgery)
- General information: Age, gender, BMI, course of disease,
comorbidities
- Laboratory tests: Blood routine, biochemical profile, coagulation
function, blood glucose, liver and kidney function
- Imaging: Lower extremity full-length standing X-ray, knee CT
(required for intervention group), MRI (if meniscus/cartilage
lesions exist)
- Kinematic assessment: 3D gait analysis (peak KAM, KAM
impulse, varus thrust)
- Functional scales: KOOS, WOMAC, OKS, Lysholm, HSS
- Safety assessment: Vital signs, electrocardiogram
- Concomitant medication record
V1
Before discharge
after surgery
- Intraoperative records: Osteotomy amount, hinge position,
fixation method, fluoroscopy times/cumulative radiation dose,
operation duration, blood loss
- Postoperative imaging: Knee X-ray (including HKA, MPTA,
PTS measurement)
- Complication monitoring: Bleeding, infection, neurovascular
injury, fracture, etc.
V2
6±1
weeks
postoperatively
- Imaging: Knee X-ray (bone healing, alignment maintenance)
- Functional assessment: ROM, weight-bearing ability
-
Complication
monitoring:
Incision
healing,
deep
vein
thrombosis, infection
- Medication and rehabilitation compliance record
V3
3
months
postoperatively
(±2 weeks)
- Imaging: Lower extremity full-length standing X-ray (HKA,
MPTA, JLCA, PTS)
- Functional assessment: KOOS, WOMAC, OKS, Lysholm, HSS

- Complication monitoring and rehabilitation progress
- Record reintervention
V4
6
months
postoperatively
(±2 weeks)
- Kinematic assessment: Gait analysis (peak KAM, KAM
impulse, varus thrust)
- Functional assessment: Same as V3
- Imaging: Lower extremity full-length standing X-ray
- Complication/reintervention record
V5
12±1
months
postoperatively
(primary endpoint
assessment)
- Kinematic assessment: Gait analysis (peak KAM%Δ, KAM
impulse, varus thrust)
- Imaging: Lower extremity full-length standing X-ray (HKA hit
rate, PTS error)
- Functional scales: KOOS, WOMAC, OKS, Lysholm, HSS
(calculate MCID compliance rate)
- Perioperative and long-term complication record
5.3 Data and Quality Control
(1)
Data at each visit point are entered into the EDC system and double-checked;
(2)
Imaging and kinematic analysis are completed by independent assessors unaware of grouping
information;
(3)
A research progress and quality control meeting is held quarterly to ensure follow-up rate and data
integrity.
5.4 Randomization and Blinding
(1)
Kinematic vs. Traditional Alignment: 1:1 randomization; assessor blinding.
(2)
3D-Printed Guide Plate vs. Traditional HTO: 1:1 randomization; imaging and function assessor
blinding.
(3)
CT Planning Optimization vs. Conventional Planning: 1:1 randomization; postoperative imaging
accuracy analysis by blinded measurement.
(4)
AR Feedback vs. Traditional Fluoroscopy: 1:1 randomization; postoperative imaging and function

assessor blinding.
(5)
The completed study (neutral vs. traditional alignment) is a prospective randomized controlled
design, and the results are used as methodological and effect size references, not included in the
current random sequence.
5.5 Other
5.5.1 Drug and Device Information
(1)
Trial Devices:

Personalized
3D-printed
osteotomy
guide
plate (PSI): Designed
based
on preoperative
high-resolution CT data 3D reconstruction and optimized planning, printed with medical-grade
polyamide, in line with national Class III medical device registration requirements, and used once
after sterilization.

AR intraoperative real-time feedback navigation system: Adopts registered and verified
augmented reality visualization platform, with functions of image superimposed display and
real-time measurement of alignment deviation.

Locking plate and screw: Medical titanium alloy material, certified by CE or NMPA.
(2)
Routine Medications:

Perioperative antibiotics (e.g., cephalosporins): Intravenous administration 30–60 minutes before
surgery, discontinued within 48 hours after surgery; other sensitive antibiotics are selected if there
is a drug allergy history.

Anticoagulants: Subcutaneous injection of low molecular weight heparin sodium after surgery,
once a day, then changed to oral anticoagulants (e.g., rivaroxaban) until 4 weeks after surgery;
specific plan adjusted according to patient risk stratification.

Analgesics: Select NSAIDs (e.g., celecoxib) or short-term weak opioids if necessary according to
VAS pain score.
5.5.2 Drug Reduction, Delay and Discontinuation Procedures
(1)
Antibiotics: If allergic reactions (rash, dyspnea, hypotension, etc.) occur after surgery, discontinue
immediately and replace with sensitive alternative drugs; if there is no evidence of infection after
surgery, discontinue strictly according to 48 hours.
(2)
Anticoagulants: If active bleeding, platelets <50×10⁹/L, or severe coagulation dysfunction occurs,

discontinue immediately and give symptomatic treatment; if high-risk factors (e.g., severe venous
thrombosis) occur in the early postoperative period, anticoagulation time can be extended.
(3)
Analgesics: If severe gastrointestinal reactions, renal impairment, or drug allergy occur, adjust or
discontinue NSAIDs, and give gastric mucosal protectants or change analgesic plans.
5.5.3 Measures to Ensure Subject Compliance
(1)
Preoperative education: The research team explains the study process, intervention measures, and
follow-up requirements to subjects and their families in detail, and provides written instructions
and education manuals.
(2)
Digital follow-up: Rely on the hospital follow-up management system or designated personnel to
regularly send visit reminders, rehabilitation guidance, and medication prompts.
(3)
Specialized follow-up: Each subject is assigned a fixed research coordinator responsible for
regular telephone/video follow-up, answering patient questions, and supervising medication and
rehabilitation compliance.
(4)
Compliance monitoring: Record the patient's actual medication, rehabilitation implementation,
and follow-up completion rate at each visit point; individualized intervention and supervision for
subjects with insufficient compliance.
6. Outcome Measures and Evaluation Methods
Including primary study endpoints (usually 1), secondary study endpoints (not limited to 1), safety
endpoints, exploratory endpoints, and their corresponding evaluation methods.
6.1 Primary Study Endpoint
Relative reduction rate of KAM (%ΔKAM): The percentage of relative reduction in peak KAM
measured by gait analysis at 12±1 months postoperatively compared with preoperative baseline,
reflecting the functional improvement of lower limb load redistribution in clinical practice.

Evaluation method: A 3D gait analysis system (Vicon or equivalent with ≥100 Hz acquisition
frequency) is used to collect walking data of subjects at self-selected speed, and the peak
adduction moment during the gait cycle is calculated. The average value of three valid gait steps
on both sides is taken, and %ΔKAM is calculated by comparing with baseline.
6.2 Secondary Study Endpoints

(1)
Static alignment accuracy: MPTA planned-actual difference (measured by knee X-ray at 6 weeks
postoperatively); HKA accuracy rate (proportion of HKA falling within ±2° target range in
full-length standing X-ray at 12 months postoperatively).
(2)
Sagittal control ability: PTS error value (difference between 12 months postoperatively and
preoperative planning value, unit: °).
(3)
Dynamic load indicators: KAM impulse (gait analysis integral value, reflecting cumulative joint
load); Varus thrust amplitude (instantaneous coronal knee angle change in gait analysis).
(4)
Patient-reported outcomes (PROs): Changes in KOOS, WOMAC, OKS, Lysholm, HSS scores
and MCID compliance rate.
(5)
Perioperative efficiency and radiation exposure: Operation time (minutes), intraoperative
fluoroscopy times.
(6)
Reoperation rate: Proportion of reoperation due to alignment failure, fracture, implant problems,
etc., within 12 months of follow-up.
6.3 Safety Endpoints
(1)
Incidence of complications during perioperative period (≤30 days) and follow-up period (≤12
months): Including incision infection, deep vein thrombosis, fracture, neurovascular injury,
nonunion, loss of correction, internal fixation failure, etc.
(2)
Incidence of serious adverse events (SAE): Death, life-threatening events, permanent functional
loss, need for hospitalization or prolonged hospitalization, congenital abnormalities, etc.
(3)
Changes in laboratory safety indicators: Proportion of significant abnormalities in blood routine,
liver and kidney function, and coagulation function before and after surgery.
6.4 Exploratory Endpoints
(4)
Correlation between alignment accuracy and clinical outcomes: Correlation between MPTA/HKA
error and %ΔKAM, PROs score improvement.
(5)
Economic indicators: Direct medical costs, reoperation costs, rehabilitation cycle, etc., between
intervention group and control group.
(6)
Relationship between AR navigation registration error and adjustment time: Explore the
correlation between intraoperative AR system accuracy and operation efficiency.

6.5 Summary of Evaluation Methods
(1)
Imaging indicators: Full-length standing X-ray and CT before surgery, 6 weeks, 3 months, 6
months, and 12 months after surgery are completed by two independent assessors unaware of
grouping information using standardized measurement methods, and the average value is taken as
the final result.
(2)
Kinematic indicators: 3D gait analysis is completed by the same center and the same measurer
using calibrated motion capture and force measurement system.
(3)
Functional scores: Recorded by trained assessors through face-to-face or video visits to ensure the
integrity of questionnaires.
(4)
Safety monitoring: All adverse events are recorded in the case report form (CRF) and electronic
data capture system (EDC), and regularly reviewed by the Data Safety Monitoring Board
(DSMB).
7. Statistical Analysis
7.1 Sample Size Estimation
The primary endpoint of this study is the relative reduction rate of peak knee adduction moment
(KAM) at 12 months postoperatively (%ΔKAM), designed as a multicenter, three-group parallel
randomized controlled trial (kinematic alignment group, traditional alignment group, dynamic
dual-mode alignment group), mainly analyzing the difference in %ΔKAM between groups.
Sample size calculation is completed using G*Power software, based on intergroup effect size f =
0.25 (medium effect size). According to previous pilot studies and previous literature reports (Katagiri
2023; our team's 2024 clinical data), the expected difference in %ΔKAM between the intervention
group (dynamic dual-mode alignment optimization) and the traditional alignment group at 12 months
postoperatively is Δ = 15%, and the standard deviation (σ) is about 20%. Setting significance level
α=0.05 (two-tailed) and test power 1-β=0.80, calculated according to one-way analysis of variance
(ANOVA) model, the required sample size per group is 34 cases. Considering that multiple group
comparisons need Bonferroni correction (α'=0.05/3 ≈0.0167), the required sample size per group is
increased to n≈40 cases after recalculation.
To ensure study power and consider about 20% loss to follow-up or dropout rate, the final
determination is: 50 cases per group; total sample size: 150 cases (3 groups).

7.2 Statistical Analysis of Study Data
Corresponding datasets (e.g., full analysis set, per-protocol set, and safety analysis set) can be
selected for study endpoint analysis; corresponding data description forms and statistical analysis
methods are selected according to endpoint evaluation indicators. The following data description forms
and statistical analysis methods are for reference:
7.2.1 Analysis Datasets
(1)
Full Analysis Set: Follows the intention-to-treat (ITT) principle, including all subjects randomly
assigned and receiving at least one intervention; missing data is handled by multiple imputation.
(2)
Per-Protocol Set (PPS): Includes subjects who strictly completed the intervention and main
follow-up according to the study protocol, used to verify the robustness of study results.
(3)
Safety Set (SS): Includes all subjects who received at least one study intervention and have safety
assessment data, used for safety endpoint analysis.
7.2.2 Data Description
(1)
Continuous variables: Describe the number of cases (n), mean (x̄), standard deviation (SD),
median (M), 25th and 75th percentiles (P25, P75), minimum (Min), and maximum (Max).
(2)
Categorical variables: Describe the number of cases (n) and percentage (%) of each category.
7.2.3 Statistical Methods
(1)
Distribution test: Shapiro-Wilk test is used to evaluate the normality of continuous variables, and
Levene test is used to evaluate variance homogeneity.
(2)
Intragroup pre-post comparison: Paired t-test is used if normally distributed; Wilcoxon
signed-rank test is used if not normally distributed.
(3)
Intergroup comparison: One-way analysis of variance (ANOVA) is used if normally distributed
and homogeneous variance, with Bonferroni multiple comparison correction if necessary;
Kruskal-Wallis H test is used if not normally distributed or heterogeneous variance, and Dunn
method is used for pairwise comparison after test.
(4)
Categorical variable comparison: Chi-square test is used; Fisher's exact probability method is used
when expected frequency <5.
(5)
Repeated measurement data (e.g., VAS, KOOS, WOMAC multi-timepoint data): Linear
mixed-effects model (LMM) is used to analyze time effect, group effect, and their interaction,

with random effect term to control individual differences.
(6)
Correlation analysis: Pearson or Spearman correlation coefficients are used to analyze the
correlation between alignment accuracy and clinical outcomes.
(7)
Consistency analysis (for comparison between planning and actual values): Bland-Altman method
is used to calculate 95% limits of agreement, and intraclass correlation coefficient (ICC) is
calculated to evaluate measurement reliability.
7.2.4 Statistical Significance
Unless otherwise specified, all statistical tests use two-tailed tests, with significance level set at α
= 0.05, and P < 0.05 is considered statistically significant. All analyses are completed using SPSS 26.0
(IBM Corp., Armonk, NY, USA) and R 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria)
software.
8. Study Risks and Disposal Plans
This study is a multicenter clinical interventional study involving HTO, personalized 3D-printed
guide plates, AR intraoperative navigation, and gait analysis. The following risks and corresponding
disposal measures may exist:
8.1 Surgery-Related Risks
(1)
Risks: Intraoperative bleeding, infection, neurovascular injury, fracture, nonunion or delayed
union of osteotomy, implant failure, accelerated degeneration of lateral compartment cartilage,
etc.
(2)
Disposal Plans:

Strictly screen subjects and exclude high-risk patients (e.g., severe osteoporosis, systemic
infection, severe comorbidities).

Surgeons must be chief doctors with rich HTO experience and familiar with PSI guide plate and
AR navigation operation procedures.

Follow aseptic principles during surgery, and prepare blood products if necessary; in case of
neurovascular injury, perform microsurgical repair or vascular reconstruction immediately.

For patients with delayed union or pseudarthrosis, give secondary intervention to promote bone
healing (bone grafting, bone stimulation therapy, etc.).
8.2 Device Application-Related Risks

(1)
Risks: Positioning deviation of PSI guide plate or AR navigation may reduce osteotomy accuracy
and affect postoperative alignment; guide plate material allergy or foreign body reaction.
(2)
Disposal Plans:

All devices have passed medical device registration certification and are strictly disinfected and
sterilized before use.

Perform guide plate fitting and simulation exercise before surgery to ensure complete fit with the
patient's bone surface.

If large positioning deviation is found during surgery, immediately switch to traditional
intraoperative fluoroscopy and mechanical axis measurement for correction.

For patients with material allergy, replace with non-sensitizing material guide plate before
surgery.
8.3 Drug Use-Related Risks
(1)
Risks: Perioperative antibiotics may cause allergic reactions or drug resistance; anticoagulants
may increase bleeding risk; NSAIDs may cause gastrointestinal adverse reactions.
(2)
Disposal Plans:

Inquire about drug allergy history before surgery and perform necessary skin tests.

Anticoagulation plan is formulated according to patient's thrombosis risk stratification, and
platelets and coagulation function are regularly monitored.

For patients with peptic ulcer or high risk, combine with gastric mucosal protectants or select
selective COX-2 inhibitors.
8.4 Imaging and Gait Analysis-Related Risks
(1)
Risks: Fall risk during gait analysis; radiation exposure from imaging examinations.
(2)
Disposal Plans:

Arrange special personnel for protection during gait analysis and lay anti-slip mats on the ground.

Imaging examinations follow the principle of "minimum necessary radiation," and low-dose mode
is used as much as possible to reduce repeated shooting.
8.5 Data and Privacy Risks
(1)
Risks: Personal privacy and medical data of subjects may be leaked.

(2)
Disposal Plans:

All data are replaced with unique codes instead of subject identity information and stored in an
encrypted electronic data capture system.

Data access is limited to authorized members of the research team, who sign confidentiality
agreements.
8.6 Emergency Handling Mechanism
Each center sets up an emergency disposal team composed of multidisciplinary personnel from
orthopedics, anesthesiology, critical care medicine, radiology, etc. In case of serious adverse events,
report to the ethics committee and data safety monitoring committee within 24 hours, and start the
emergency treatment process until the incident is resolved. Regularly conduct risk prevention and
emergency disposal training for the research team to ensure that all types of emergencies can be
handled in a timely and standardized manner.
9. Study Termination Criteria
To ensure the safety of subjects and maintain the scientificity and data integrity of the study, the
entire study or individual subjects' participation in the study should be terminated when one of the
following situations occurs:
9.1 Subject Safety-Related Reasons
(1)
Any clinical adverse event (AE), severe abnormal laboratory test, or new comorbidity that the
researcher believes will cause unacceptable risks to the subject or is not in their best interest if
they continue to participate in the study.
(2)
Severe adverse events (SAE) occur after surgery, which are highly correlated with study
intervention after comprehensive evaluation, and continued study may lead to serious
consequences.
9.2 Study Implementation and Methodology-Related Reasons
(1)
Blind bottom leakage occurs (applicable to sub-studies implementing blinding), making it
impossible to ensure the scientificity and fairness of results.
(2)
Researchers or research centers seriously fail to comply with the study protocol (e.g., intervention
operation, evaluation method, drug use, etc.) and cannot be corrected in time, affecting the

validity and comparability of study data.
(3)
The Data Safety Monitoring Board (DSMB) finds that the primary endpoint cannot achieve the
expected effect or there is a significant adverse trend opposite to the expected during regular
evaluation.
9.3 Ethics and Management-Related Reasons
(1)
The ethics committee requires the termination of the study based on safety, scientificity, or ethical
principles.
(2)
Higher management departments or funders issue termination orders due to major safety hazards,
data quality problems, or policy adjustments in the study.
9.4 Subject's Personal Will
The subject or their legal representative proposes to voluntarily withdraw from the study and
confirms after informed notification.
9.5 Termination Handling Process
Once a study termination situation occurs, researchers should immediately take measures to
protect the safety of subjects and provide corresponding medical treatment if necessary. The reasons for
termination and related materials must be detailed in the case report form (CRF) and electronic data
capture system (EDC), and reported to the ethics committee and relevant regulatory authorities within
24 hours. Conduct a final follow-up on enrolled subjects and record their clinical status and outcomes.
10. Adverse Events and Disposal
Serious Adverse Event (SAE): refers to an adverse medical event that results in death, is
life-threatening, causes permanent or severe disability or functional loss, requires hospitalization or
prolongation of hospitalization, or is a congenital anomaly or birth defect in a subject after receiving
the test drug.
Once an SAE occurs, the researcher shall report it within 24 hours after discovery and submit the
SAE report form to the clinical research ethics committee for review of the adverse event, and record it.
For death cases, report to the medical department in a timely manner in accordance with hospital
regulations.

Treatment measures: Researchers need to take immediate measures to ensure that subjects receive
timely clinical treatment, and follow up the outcome of their SAE until recovery or return to the
baseline level.
11. Quality Control
Researchers will adopt standard operating procedures to ensure the implementation of the quality
control and quality assurance system for clinical research. All observations and findings in clinical
research will be verified to ensure data reliability and ensure that all conclusions in clinical research are
derived from original data. Quality control is adopted at each stage of data processing to ensure that all
data are reliable and processed correctly.
12. Ethical Requirements
(1)
Before the start of the clinical study, the study protocol must be reviewed by the ethics committee,
and the study can be implemented only after the review result is approved and a approval letter is
signed.
(2)
During the study, the WMA Declaration of Helsinki (2013), CIOMS International Ethical
Guidelines for Biomedical Research Involving Human Subjects (2016), and National Health
Commission Measures for the Ethical Review of Life Science and Medical Research Involving
Humans (2023) shall be followed.
(3)
During the study, any modification of the clinical study protocol, informed consent form,
recruitment materials, etc., must be approved by the ethics committee before implementation.
(4)
Before each subject is enrolled in this study, the researcher must introduce the existing treatment
methods, the purpose of this study, the study process and duration, examination operations,
expected benefits and risks of the subject, possible money and time spent, and the subject's
assignment to different groups in detail. In addition, researchers need to inform subjects that
participation in this study is completely voluntary, and they have the right to withdraw from the
study at any stage without discrimination or retaliation, and their medical treatment and rights will
not be affected.
(5)
After fully and detailed explanation of the study, the subject or their legal representative (for
subjects with incapacity) signs the informed consent form and indicates the date. The researcher
who executes the informed consent process also signs the name and date on the informed consent
form. The informed consent form is in duplicate, one for the subject and one for the researcher.

13. Expected Progress and Completion Date
This study plans to start 1 month after approval by the ethics committee, with a total study period of 24
months. The specific progress arrangement is as follows:
(1)
Preparation Stage (Months 0–3): Research team formation and training; formulation and
improvement of standard operating procedures (SOP), case report form (CRF), and electronic data
capture system (EDC); completion of ethical approval and pilot enrollment.
(2)
Enrollment and Intervention Stage (Months 4–18): Continuous case enrollment and intervention
implementation according to randomization scheme; completion of preoperative baseline
assessment, surgery, and early postoperative follow-up.
(3)
Follow-up and Data Collection Stage (Months 18–22): Completion of primary endpoint
assessment (12 months postoperatively) and other follow-ups; ensure that the completion rate of
primary endpoints is ≥90%.
(4)
Data Analysis and Conclusion Stage (Months 22–24): Data cleaning and statistical analysis;
writing research report and preparing SCI paper submission.
Expected Timeline:

Start Time: September 2025

Completion Time: August 2027
14. Participating Institutions and Responsibilities of All Parties
14.1 List of Research Centers

Leading Institution: The First Affiliated Hospital of Wenzhou Medical University

Collaborating Institutions: Beijing Jishuitan Hospital, Ningbo Sixth People's Hospital
14.2 Cooperative Units

Imaging Data Processing Laboratory: Hubei Jiayi Hi-Tech Co., Ltd.

3D-Printed Guide Plate Manufacturer: Hubei Jiayi Hi-Tech Co., Ltd.

CRO/SMO Company: Zhejiang Yaohui Pharmaceutical Technology Co., Ltd.

14.3 Responsibilities of Participating Institutions
Institution Name
Responsibilities
The
First
Affiliated
Hospital
of
Wenzhou
Medical
University
(Leading Institution)
Responsible for overall study design and protocol formulation;
undertaking
ethical
approval
and
project
registration;
coordinating the implementation of each research center;
responsible for data management and statistical analysis;
formulating unified standards for primary endpoint assessment
and training; leading paper writing and result release.
Beijing Jishuitan Hospital
Complete
subject
screening,
enrollment,
surgery,
and
follow-up according to the protocol; provide preoperative
imaging and kinematic assessment data; participate in case
quality control and difficult case discussion.
Ningbo Sixth People's Hospital
Complete
case
recruitment
and
intervention
operations
according to the protocol; cooperate in completing imaging
and gait data collection; participate in research data sharing
and safety monitoring.
Hubei Jiayi Hi-Tech Co., Ltd. (Imaging Data Processing
Laboratory)
Provide
a
unified
image
measurement
platform; independently analyze image registration and guide
plate accuracy; issue standardized analysis reports.
Hubei
Jiayi
Hi-Tech
Co.,
Ltd.
(3D-Printed
Guide
Plate
Manufacturer)
Produce personalized guide plates according to preoperative
planning documents to ensure dimensional accuracy and
qualified sterilization; provide production quality records and
technical support.
Zhejiang
Yaohui
Pharmaceutical
Technology Co., Ltd. (CRO/SMO
Company)
Assist in multicenter case management, visit arrangement, data
verification, and monitoring; ensure consistency, compliance,
and high follow-up rate of data collection in each center.