Abstract. OBJECTIVE. Knee varus malalignment increases medial knee compartment loading and is associated with knee osteoarthritis (OA) progression and severity. 1. Altered biomechanical loading and dysregulation of joint tissue biology drive OA progression, but mechanistic links between these factors are lacking. Subchondral bone structural changes are biomechanically driven, involve bone resorption, immune cell influx, angiogenesis, and sensory nerve invasion, and contribute to joint destruction and pain. 2. We have investigated mechanisms underlying this involving RANKL and alkaline phosphatase (ALP), which reflect bone resorption and mineralisation respectively. 3. and the axonal guidance factor Sema3A. Sema3A is osteotropic, expressed by mechanically sensitive osteocytes, and an inhibitor of sensory nerve, blood vessel and immune cell invasion. 4. Sema3A is also differentially expressed in human OA bone. 5. HYPOTHESIS: Medial knee compartment overloading in varus knee malalignment patients causes dysregulation of bone derived Sema3A signalling directly linking joint biomechanics to pathology and pain. METHODS. Synovial fluid obtained from 30 subjects with medial knee OA (KL grade II-IV) undergoing high tibial osteotomy surgery (HTO) was analysed by mesoscale discovery and ELISA analysis for inflammatory, neural and bone turnover markers. 11 of these patients had been previously analysed in a published patient-specific musculoskeletal model. 6. of gait estimating joint contact location, pressure, forces, and medial-lateral condyle load distribution in a published data set included in analyses. Data analysis was performed using Pearson's correlation matrices and principal component analyses. Principal Components (PCs) with eigenvalues greater than 1 were analysed. RESULTS. PC1 (32.94% of variation) and PC2 (25.79% of variation) from PCA analysis and correlation matrices separated patients according to correlated clusters of established inflammatory markers of OA pain and progression (IL6/IL8, r=0.754, p<0.001) and anti-inflammatory mediators (IL4/IL10, r=0.469, p=0.005). Bone turnover marker ALP was positively associated with KL grade (r=0.815, p=0.002) and negatively associated with IL10 (r=−0.402, p=0.018) and first peak knee loading pressures (r=−0.688, p=0.019). RANKL was positively associated with IL4 (r=0.489, p=0.003). Synovial fluid Sema3A concentrations showed separate clustering from all OA progression markers and was inversely correlated with TNF-α (r=−0.423, p=0.022) in HTO patients. Sema3A was significantly inversely correlated with total predicted force in the medial joint compartment (r=−0.621, p=0.041), mean (r=−0.63, p=0.038) and maximum (r=−0.613, p=0.045) calculated medial compartment joint pressures during the first phase and mean (r=−0.618, p=0.043) and maximum (r=−0.641, p=0.034) medial compartment joint pressures during midstance outputs of patient-specific musculoskeletal model. CONCLUSIONS. This study shows joint inflammatory status and mechanical overloading influence subchondral bone-remodelling. Synovial Sema3A concentrations are inversely correlated to patient-specific musculoskeletal model estimations of pathological medial overloading. This study reveals Sema3A as a biological mediator with capacity to induce OA pain and disease progression that is directly regulated by gait mechanical loading. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

The medial opening-wedge high tibial osteotomy (OW-HTO) is an accepted option to treat the isolated medial compartment osteoarthritis (OA) in varus knee. Despite satisfactory outcomes were described in literature, consistent complication rate has been reported and the provided accuracy of coronal alignment correction using conventional HTO techniques falls short. Patient specific instrumentations has been introduced with the aim to reduce complications and to improve the intra-operative accuracy according to the pre-operative plan, which is responsible for the clinical result of the surgery. In this talk, an overview of the clinical results of HTO patient specific instrumentation available in literature will be performed. Moreover, preliminary intra-operative and clinical results of a new customised 3-D printed cutting guide and fixation plate for OW-HTO will be presented

Abstract. OBJECTIVES. Valgus high tibial osteotomy (HTO) represents an effective treatment for patients with medial compartment osteoarthritis (OA) in a varus knee. However, the mechanisms which cause this clinical improvement are unclear. Previous studies suggest a wider stance gait can reduce medial compartment loading via reduction in the external knee adduction moment (KAM); a measure implicated in progression of medial compartment OA. This study aimed to measure whether valgus HTO is associated with a postoperative increase in static stance width. METHODS. 32 patients, recruited in the Biomechanics and Bioengineering Centre Versus Arthritis HTO study, underwent valgus (medial opening wedge) HTO. Weightbearing pre- and post- operative radiographs were taken showing both lower limbs. The horizontal distance, measured from a fixed point on the right talus to the corresponding point on the left, was divided by the talus width to give a standardised “stance width” for each radiograph. The difference between pre- and post- operative stance width was compared for each patient using a paired sample t-test. RESULTS. Preoperatively, mean stance was 4.00 talar-widths but postoperatively this increased to 5.41. This mean increase of 1.42 talar-widths was statistically significant (p=0.001) and represents a mean proportional increase in stance width of 35.5% following HTO. Of the 32 patients, 23 showed increased stance width and 9 decreased (range −4.64 to 6.00 talar-widths). CONCLUSIONS. These findings indicate an association of frontal plane surgical realignment at the proximal tibia via a medial opening wedge HTO with an increased stance width on postoperative radiographs. Considering both wider stance gait and HTO have been shown to affect the progression of medial compartment OA, these results may explain one mechanism contributing to the efficacy of HTO surgery. However, the range of changes in stance width suggests significant variability in how patients adapt at a whole-limb and whole-body level following HTO. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

A correct ligament loading following TKA surgery is believed to minimize instability and improve patient satisfaction. The evaluation of the ligament stress or strain is however impractical in a surgical setting. Alternatively, tibial trial components containing force sensors have the potential to indirectly assess the ligament loading. These instrumented components quantify the medial and lateral forces in the tibiofemoral joint. Although this method finds clinical application already, the target values for both the force magnitude and medial / lateral force ratio under surgical conditions remain uncertain. A total of eight non-arthritic cadaveric knees have been tested mimicking surgical conditions. Therefore, the specimens are mounted in a custom knee simulator. This simulator allows to test full lower limb specimens, providing kinematic freedom throughout the range of motion. Knee flexion is obtained by lifting the femur (thigh pull). Knee kinematics are simultaneously recorded by means of a navigation system and based on the mechanical axis of the femur and tibia. In addition, the load transferred through the medial and lateral compartment of the knee is monitored. Therefore, a 2.4 mm thick sawing blade is used to machine a slot in the tibia perpendicular to the mechanical axis, at the location of the tibial cut in TKA surgery. A complete disconnection was thereby assured between the tibial plateau and the distal tibia. To fill the created gap, custom 3D printed shims were inserted. Through their specific geometry, these shims create a load deviation between two Tekscan pressure pads on the medial and lateral side. Following the insertion of the shims, the knee was closed before performing the kinematic and kinetic tests. Seven specimens showed a limited varus throughout the range of motion (ranging from 1° to 7° varus). The other knee was in valgus (4° valgus). Amongst varus knees, the results were very consistent, indicating high loads in full extension. Subsequently, the loads decrease as the knee flexes and eventually vanishes on the lateral side. This leads to consistently high compartmental load ratios (medial load / total load) in flexion. In full extension the screw-home mechanism results in increased loads, both medially and laterally. Upon flexion, the lateral loads disappear. This is attributed to slackening of the lateral collateral ligament, in turn linked to the femoral rollback and slope of the lateral compartment. The isometry of the medial collateral ligament contributes on the other hand to the near-constant load in the medial compartment. The above particularly applies for varus knees. The single valgus knee tested indicated a higher load transmission by the lateral compartment, potentially attributed to a contracture of the lateral structures. With respect to TKA surgery, these findings are particularly relevant when considering anatomically designed implants. For those implants, this study concludes that a tighter medial compartment reflects that of healthy varus knees. Be aware however that in full extension, higher and up to equal loads can be acceptable for the medial and lateral compartment

Constitutional knee varus increases the risk of medial OA disease due to increase in the knee adduction moment and shifting of the mechanical axis medially. Hueter-Volkmann’s law states that the amount of load experienced by the growth plate during development influences the bone morphology. For this reason, heightened sports activity during growth is associated with constitutional varus due to added knee adduction moment. In early OA, X-rays often show a flattened medial femoral condyle extension facet (EF). However, it is unknown whether this is a result of osteoarthritic wear, creep deformation over decades of use, or an outcome of Hueter-Volkmann’s law during development. A larger and flattened medial EF can bear more weight, due to increased load distribution. However, a flattened EF may also extrude the meniscus, leading meniscus degeneration and joint failure. Therefore, this study aimed to investigate whether varus knees have flattened medial EFs of both femur and tibia in a cohort of patients with no signs yet of bony attrition. Segmentation and morphology analysis was conducted using Materialise software (version 8.0, Materialise Inc., Belgium). This study excluded knees with bony attrition of the EFs based on Ahlbäck criteria, intraoperative findings, and operation notes history. Standard reference frames were used for both the femur and tibia to ensure reliable and repeatable measurements. The hip-knee-angle (HKA) angle defined varus or valgus knee alignment. Femur: The femoral EFs and flexion facets (FFs) had best-fit spheres fitted with 6 repetitions. Tibia: The slopes of the antero-medial medial tibial plateau were approximated using lines. Results 72 knees met the inclusion and exclusion criteria. The average age was 59 ± 11 years. The youngest was 31 and the oldest 84 years. Thirty-three were male and 39 were female. There was good intra- and inter-observer reliability for EF sphere fitting. Femur: The results demonstrated that the medial femoral condyle EF is flattened in knees with constitutional varus, as measured by the Sphere Ratios between the medial and lateral EF (varus versus straight: p = 0.006), and in the scaled values for the medial EF sphere radius (varus versus straight: p = 0.005). There was a statistically significant, moderate and positive correlation between the medial femoral EF radius, and the medial femoral EF-FF AP offset. Tibia: There was a statistically significant difference between the steepness of the slopes of the medial tibial plateau EF in varus and valgus knees, suggesting varus knees have a less concave (flatter) medial EF. Conclusions In comparison to straight knees, varus knees have flattened medial EFs in both femur and tibia. As this was the case in knees with no evidence of bony attrition, this could mean flattened medial EFs may be a result of medial physis inhibition during development, due to Hueter-Volkmann’s law. Flattened medial EFs may increase load distribution in the medial compartment, but could also be a potential aetiology in primary knee OA due to over extrusion of the medial meniscus and edge loading

Hindfoot disorders are complex 3D deformities. Current literature has assessed their influence on the full leg alignment, but the superposition of the hindfoot on plain radiographs resulted in different measurement errors. Therefore, the aim of this study is to assess the hindfoot alignment on Weight-Bearing CT (WBCT) and its influence on the radiographic Hip-Knee-Ankle (HKA) angle. A retrospective analysis was performed on a study population of 109 patients (mean age of 53 years ± 14,49) with a varus or valgus hindfoot deformity. The hindfoot angle (HA) was measured on the WBCT while the HKA angle, and the anatomical tibia axis angle towards the vertical (TA. X. ) were analysed on the Full Leg radiographs. The mean HA in the valgus hindfoot group was 9,19°±7.94, in the varus hindfoot group −7,29°±6.09. The mean TA. X. was 3,32°±2.17 in the group with a valgus hindfoot and 1,89°±2.63 in the group with a varus hindfoot, which showed to be statistically different (p<0.05). The mean HKA Angle was −1,35°±2.73 in the valgus hindfoot group and 0,4°±2.89 in the varus hindfoot group, which showed to be statistically different (p<0.05). This study demonstrates a higher varus in both the HKA and TA. X. in valgus hindfoot and a higher tibia valgus in varus hindfoot. This contradicts the previous assumption that a varus hindfoot is associated with a varus knee or vice versa. In clinical practice, these findings contribute to a better understanding of deformity corrections of both the hindfoot and the knee

Background. New marker free motion analysis systems are being used extensively in the area of sports medicine and physiotherapy. The accuracy and validity of use in an orthopaedic setting have not been fully assessed for these newer marker free motion analysis systems. The aim of this study is to compare leg length and varus/valgus knee measurements performed by leg measurement x-ray, and performed using the new marker free motion analysis system (Organic motion biostage). Methods. Patients attending the orthopaedic department for total knee replacements were recruited. They underwent radiological leg measurement x-ray, clinical leg measurement, and finally assessment using the organic motion biostage system. These were analysed using the motion monitor software, microsoft excel and minitab 16. Results. For 23 patients assessed, all methods showed a statistically significant result (p<0.05) using paired t-tests. This rejects the null hypothesis- indicating that organic motion does not have the accuracy currently to measure leg length or knee varus/valgus angle. Conclusions. Results indicate that the organic motion biostage system- a new marker free motion analysis system, is not feasible currently as a method of accurately measuring leg-length. Given the current modelling methods used by this new system there are limitations, that if addressed may yet allow the system to become a useful clinical tool. These authors feel it still has applications in orthopaedics as a useful, quick, and easy to use method of motion analysis and functional screen in orthopaedic patients, and warrants further investigation. We also present a case of lumbar pedicle subtraction osteotomy, and show how markerless motion analysis is a useful tool for assessing spinal sagittal balance, and its effect on the biomechanics of walking. Level of Evidence. IV

Summary Statement. An MRI-derived subject-specific finite element model of a knee joint was loaded with subject-specific kinetic data to investigate stress and strain distribution in knee cartilage during the stance phase of gait in-vivo. Introduction. Finite element analysis (FEA) has been widely used to predict the local stress and strain distribution at the tibiofemoral joint to study the effects of ligament injury, meniscus injury and cartilage defects on soft tissue loading under different loading conditions. Previous studies have focused on static FEA of the tibiofemoral joint, with few attempts to conduct subject-specific FEA on the knee during physical activity. In one FEA study utilising subject-specific loading during gait, the knee was simplified by using linear springs to represent ligaments. To address the gap that no studies have performed subject-specific FEA at the tibiofemoral joint with detailed structures, the present study aims to develop a highly detailed subject-specific FE model of knee joint to precisely simulate the stress distribution at knee cartilage during the stance phase of the gait cycle. Method. A detailed three-dimensional model of a healthy human knee was developed from MRI images of a living subject, including the main anatomical structures (bones, all principal ligaments, menisci and articular cartilages). The femur, tibia and fibula were considered as rigid bodies, while the menisci and articular cartilage were modelled as linearly elastic, isotropic and homogeneous while the ligaments were considered to be hyperelastic. Loading and boundary condition assignment was based on the kinematic and kinetic data recorded during gait analysis. Ten time intervals during the stance phase of gait were separately simulated to quantify the time–dependent stress distribution throughout the cycle from heel-strike to toe-off. Loading condition of the tibiofemoral joint varys during the gait cycle since the joint angle changes from extension to flextion, therefore different joint angles at relative time interval were determined to accurately simulate the varing loading condition. Results. The compressive stress and tensile strain distributions in the femoral cartilage, tibia cartilage and menisci of each selected time interval during the stance phase of gait cycle were quantified and corresponded to specific amount of varus/valgus knee moment obtained by inverse dynamics analysis of the kinematic and kinetic data from gait analysis. Therefore a correlation between stress/strain and the frontal movement was established and analysed. For example, at 10% of stance phase, the stress concentration was observed on the lateral compartment due to the valgus moment created at heel strike. At the next interval, the stress concentration shifted to the medial side as the frontal knee moment shifted to a varus orientation. Discussion. The results suggest that the stress distribution of tibiofemoral articular cartilage is qualitatively consistent with the valgus and varus moment observed during the stance phase of gait. The methods described could be applied to investigate the effects of injury and reconstruction on stress distribution within the tibiofemoral joint

The understanding of rotational alignment of the distal femur is essential in total knee replacement to ensure that there is correct placement of the femoral component. Many reference axes have been described, but there is still disagreement about their value and mutual angular relationship. Our aim was to validate a geometrically-defined reference axis against which the surface-derived axes could be compared in the axial plane. A total of 12 cadaver specimens underwent CT after rigid fixation of optical tracking devices to the femur and the tibia. Three-dimensional reconstructions were made to determine the anatomical surface points and geometrical references. The spatial relationships between the femur and tibia in full extension and in 90° of flexion were examined by an optical infrared tracking system.

After co-ordinate transformation of the described anatomical points and geometrical references, the projection of the relevant axes in the axial plane of the femur were mathematically achieved. Inter- and intra-observer variability in the three-dimensional CT reconstructions revealed angular errors ranging from 0.16° to 1.15° for all axes except for the trochlear axis which had an interobserver error of 2°. With the knees in full extension, the femoral transverse axis, connecting the centres of the best matching spheres of the femoral condyles, almost coincided with the tibial transverse axis (mean difference −0.8°, sd 2.05). At 90° of flexion, this femoral transverse axis was orthogonal to the tibial mechanical axis (mean difference −0.77°, sd 4.08). Of all the surface-derived axes, the surgical transepicondylar axis had the closest relationship to the femoral transverse axis after projection on to the axial plane of the femur (mean difference 0.21°, sd 1.77). The posterior condylar line was the most consistent axis (range −2.96° to −0.28°, sd 0.77) and the trochlear anteroposterior axis the least consistent axis (range −10.62° to +11.67°, sd 6.12). The orientation of both the posterior condylar line and the trochlear anteroposterior axis (p = 0.001) showed a trend towards internal rotation with valgus coronal alignment.