Coronal Plane Alignment Of The Knee (CPAK) Type III Valgus Knee Exhibits Lateral Pivot Motion During Squatting

Coronal Plane Alignment Of The Knee (CPAK) Type III Valgus Knee Exhibits Lateral Pivot Motion During Squatting | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Coronal Plane Alignment Of The Knee (CPAK) Type III Valgus Knee Exhibits Lateral Pivot Motion During Squatting Geert Peersman, Orçun Taylan, Junya Itou, Gérard Peersman, Johan Bellemans, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6385860/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Medial pivoting motion has been identified as the primary kinematic pattern throughout flexion of the native knee joint. The recently introduced coronal plane alignment of the knee (CPAK) classification categorizes knees into nine alignment-based phenotypes, yet the relationship between these phenotypes and their respective kinematic behavior remains poorly documented, particularly in less common valgus phenotypes. Therefore, this study aimed to perform a detailed analysis of the pivoting motion of the CPAK type III knees during ex vivo simulated squatting. Considering the more lateral weight-bearing axis in the valgus phenotype, we hypothesized that weight-bearing motion is associated with lateral pivot motion. We retrospectively analysed a previously collected dataset of sixty-nine native fresh-frozen cadaveric knees subjected to squatting motion (35°-100°) on a physiological knee joint simulator. Seventeen CPAK Type III knees were identified based on full-leg computed tomography scans. Next, we discerned between medial and lateral pivoting throughout the range of motion based on the location of the instantaneous center of rotation (ICOR) to the center of the tibial plateau. Furthermore, we screened for possible associations between CPAK’s coronal lower limb alignment features and lateral pivoting. All 17 CPAK type III knees exhibited a lateral center of rotation during squatting, with 8 demonstrating lateral pivoting as the predominant pattern over more than half of the flexion range. This study showed that a lateral pivot motion pattern occurred during squatting in approximately half of the CPAK type III specimens, from mid to deep flexion (58.5°-100°) when tested in a loaded knee simulator. The current study offers essential data and insights to be considered for subsequent research on the role of native valgus knee kinematics in optimizing TKA outcomes. Health sciences/Anatomy Health sciences/Medical research Physical sciences/Physics lateral pivot coronal plane alignment of the knee (CPAK) valgus squatting kinematics Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Total knee arthroplasty (TKA) is considered the gold standard treatment for relieving pain and restoring knee function in patients with knee osteoarthritis (OA) 1 , 2 . Unfortunately, it is also true that not everyone who has undergone TKA is satisfied 3 – 5 . Although the exact reasons for this may be diverse, it could be assumed that patient satisfaction is correlated with the TKA’s ability to restore kinematics more closely to the native knee 6 , 7 . Hence, understanding native knee kinematics and its phenotypes is warranted to further improve clinical outcomes and patient satisfaction. Prior research has identified a medial pivoting motion as the main kinematic pattern throughout flexion of the native knee joint 8 . Based hereon, medial pivot-type prosthesis designs have been introduced to restore preoperative kinematics and, indeed, excellent clinical outcomes have been reported for varus knees 9 . Recently, the coronal plane alignment of the knee (CPAK) classification was introduced by MacDessi et al. 10 which categorizes all knees into nine alignment-based phenotypes and is intended to enhance TKA planning with the patient’s constitutional limb alignment in mind. Furthermore, CPAK types I and II, i.e. varus knees, were reported to be the most common phenotype in both healthy and arthritic populations, whereas only 2.4–28.4% have been classified as CPAK types III, VI or IX, i.e. valgus knees 11 – 15 . Nevertheless, the association between these alignment-based phenotypes and their respective kinematic behavior has not been adequately evaluated. Indeed, prior studies documenting native knee kinematics did not base their evaluation of lower extremity alignment yet on alignment-phenotypes such as the CPAK classification. As a result, the identification of medial pivoting as the main kinematic pattern might have been biased by the more common varus-aligned phenotypes and its applicability to the less common valgus-aligned phenotypes thus remains to be confirmed. Within this context, prior research did already establish that knees with varus and valgus deformities exhibit different kinematic patterns 16 , 17 . Some authors have suggested that these differences may be primarily associated with the varying alignment of the lower-limbs weight-bearing axis leading to a more medial tibiofemoral contact point in varus knees versus a more lateral contact point in valgus knees 18 , 19 . Indeed, in contrast to the traditional belief that knees solely exhibit a medial pivoting kinematic behavior 8 , more recent studies have reported a more variable pivoting behavior throughout the full knee range of motion 20 – 24 . For example, Meneghini et al. have stated that during activities of daily living, such as walking, running, or pivoting the native knee exhibits a lateral pivot pattern in earlier knee flexion, whereas medial pivoting occurred during deeper knee flexion 25 . However, also here the association between native knee kinematics and CPAK’s phenotypes was not documented. Our current understanding of how native weight-bearing kinematics are related to an individual’s constitutional alignment as expressed in the CPAK classification, remains to be fully investigated, specifically in terms of its pivoting motion in the less common valgus phenotypes. Gaining insight into the pivoting motion patterns, especially in the valgus knees, may greatly help surgeons determine an optimal treatment strategy. Moreover, its restoration in TKA may, in theory, result in better patient outcomes and increased patient satisfaction. Therefore, this study aimed to perform a detailed analysis of the pivoting motion of CPAK type III knees as the most common valgus phenotype 10 , 11 , during ex vivo simulated squatting. Considering the more lateral weight-bearing axis in the valgus knee, it was hypothesized that the weight-bearing squatting motion could be associated with a more dominant lateral pivot motion Materials and Methods For this study we retrospectively analysed a previously collected dataset documenting tibiofemoral kinematics of sixty-nine native fresh-frozen cadaveric knees (Table 1 ) that were subjected to passive flexion and squatting motions; the latter using a single physiological ex vivo knee simulator, between 2014 and 2023. All specimens were tested following ethical approval with a consistent, well-established method briefly outlined hereunder (Fig. 1 ) 26 . Table 1 Demographics of the specimens, including the Coronal Plane Alignment of the Knee (CPAK) classification, number of the samples, age distribution, gender (%), height, weight, and size of the tibial plateau in anterior-posterior and medial-lateral directions. CPAK Type Number Age Gender (Male %) Height Weight Medial AP Lateral AP Mediolateral ML I 10 85 ± 10 80 171.8 ± 7.4 81.3 ± 9 44.98 ± 3.79 36.62 ± 3.06 76.54 ± 5.57 II 33 81.1 ± 9.2 63.6 170.1 ± 7.7 72 ± 14.2 43.31 ± 3.59 37.41 ± 4.45 76.95 ± 5.09 III 17 79.8 ± 8.82 52.9 170.9 ± 8.8 75.4 ± 19.3 43.2 ± 4.03 37.51 ± 4.26 75.86 ± 5.55 V 4 81.7 ± 11.3 75 179 ± 13.4 89 ± 17.4 45.13 ± 4.04 38.41 ± 3.06 78.19 ± 5.32 VI 5 79.4 ± 5.4 60 171.4 ± 5.9 77.2 ± 16.6 46.61 ± 0.67 37.97 ± 2.14 79.17 ± 5.76 Medial AP = Medial tibial plateau anterior−posterior size (mm); Lateral AP = Lateral tibial plateau anterior−posterior size (mm); ML = Mediolateral size of tibial plateau (mm); the values with “±” indicate mean ± standard deviation Prior to the testing, bi-cortical bone pins were inserted into the femur and tibia to attach rigid frames containing four retroreflective spheres. Non-weight-bearing computed tomography (CT) scans were acquired from the specimens in full extension with a slice thickness of 0.6–0.75 mm (Fig. 1 A). The CT scans and available lab notes were screened by an experienced surgeon for possible signs of severe OA (i.e. equilavent to Kellgren and Lawrence grade 3 and grade 4) or pathology that might have affected the kinematic behavior (e.g. fracture history). Based hereon, ten (n = 10) out of the sixty-nine (n = 69) specimens were excluded. Next, segmentation software (Mimics 25.0, Materialise, Leuven, Belgium) was used to identify the location of the spherical markers, as well as specific anatomical landmarks 27 to define a joint coordinate system for the femur and tibia based on the Grood and Suntay conventions (Fig. 1 B) 28 . Identification of CPAK Type III Knees Each specimen’s CT scan was imported into Mimics (Materialise, Leuven, Belgium), and 3-D models of the femur and tibia were generated. Detailed reconstructions were performed for the distal femur and proximal tibia to allow accurate definition of the required landmarks. More specifically, the following femoral and tibial anatomical landmarks were identified as described by Victor et al 27 (Fig. 1 B). For the femur, the mechanical axis (vertical axis) was defined by the line between the femoral hip center (FHC) and the femoral knee center (FKC). The femoral medio-lateral axis was defined by a line between the femoral medial condyle center (FMCC) and the femoral lateral condyle center (FLCC). The anterior-posterior axis of the femur was defined as the axis that is mutually perpendicular to both the mechanical axis and the medio-lateral axis of the femur. The tibial mechanical axis was defined as the line between the center of the tibial plateau (TKC) and the ankle joint (TAC). The tibial medio-lateral axis was defined by a line from the point of the medial condyle center (TMCC) to the lateral condyle center (TLCC). Consequently, the anterior-posterior axis was defined as the line mutually perpendicular to these two axes. The above vertical and medio-lateral axes definitions were then used to define the coronal plane for both the femur and tibia. Next, the lateral distal femoral angle (LDFA) and the proximal tibial angle (MPTA) were calculated. The LDFA was defined as the angle on the lateral side between the femoral mechanical axis and the joint line of the distal femur 10 projected on the coronal plane (Fig. 1 C). To define the joint line, the most distal points of the medial and the lateral femoral condyles were identified 15 . Similarly, the MPTA was described as the angle on the medial side between the tibia’s mechanical axis and the coronal plane projection of the joint line of the proximal tibia, defined as the line connecting the deepest points of the medial and lateral tibial plateau (Fig. 1 C) 29 . To determine the CPAK classification for each knee, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated based on the LDFA and MPTA 10 . Accordingly, the aHKA was calculated as the difference between MPTA and LDFA, while JLO was the sum of MPTA and LDFA. The bony landmark identification and CPAK phenotyping were performed by an experienced knee surgeon who was not involved in the experimental data collection and was blinded to the sample identifications. Experimental Protocol All specimens were thawed 24 hours prior to testing, with a maximum of two freezing-thawing cycles. The femur and tibia were resected 320 mm proximal and 280 mm distal to the knee joint line, respectively. The skin and subcutaneous tissue surrounding the knee joint were carefully removed while preserving the joint capsule, ligaments and tendons. The exposed quadriceps tendon was clamped within a custom metal clamp, and suture loops (2x2 non-absorbable polyester braided suture wire; Cardioxyl, Peters Surgical, Bobigny Cedex, France) were passed through the medial and lateral hamstrings. Subsequently, the femur and tibia were embedded into metal containers using acrylic resin (Struers, Ballerup, Denmark), with the femur positioned in 6° of valgus. Each specimen was mounted into an Oxford-based dynamic ex vivo knee simulator and subjected to loaded squatting (35° – 100°). During squatting motion, 50 N constant force springs were attached to the medial and lateral hamstrings suture loops to apply a constant load throughout the entire flexion cycle, while the quadriceps clamp was fixed to a linear actuator. The force of the electromechanical quadriceps actuator was computer-controlled to apply physiological quadriceps load while maintaining a vertical ankle load of 110 N. Each motion was performed in triplicate, and the trajectories of the retro-reflective spheres attached to the specimens were recorded using six infrared cameras (Vicon Motion Systems, Oxford, UK) operating at 100 Hz. Identification of Medial or Lateral Pivoting Motion The trajectories of the bone-pin mounted reflective markers were reconstructed in 3D (Nexus 2.9, Vicon, Oxford, UK). Based hereon, tibiofemoral translations and rotations during squatting were computed with custom-written code in Matlab (R2018b, Mathworks Inc, Natick, MA, USA). Each kinematic variable was down-sampled and interpolated at intervals of 1° of flexion and within the common range of knee flexion shared by all specimens for squatting (35° – 100°). To determine the instantaneous center of rotation (ICOR) during squatting, the medial-lateral axis of the femur was projected onto the transverse plane of the tibia. For each consecutive pair of knee flexion angles, the intersection points of the medial-lateral axis of the femur projected onto the tibial plateau were calculated, resulting in the ICORs as a function of knee flexion angle, as described by Koo and Andriacchi 21 . These points provided a detailed pattern of how the center of rotation changed during knee flexion (Fig. 2 ). Next, we discriminated between medial and lateral pivoting motion throughout the flexion range of squatting motion based on the medio-lateral position of the ICOR with respect to the TKC: if the ICOR was medial or lateral to the TKC, the associated flexion angle was identified as demonstrating medial or lateral pivoting, respectively. Finally, a density plot was created to visualize the medio-lateral distribution of the ICORS location as a function of the flexion angle for those specimens classified as CPAK type III (Fig. 4 A). In addition, the proportion of lateral pivoting relative to total pivoting (medial + lateral) was assessed for each specimen across the full range of motion (35° – 100°). The percentage of lateral pivoting was calculated to further classify specimens. If more than 50% of the total pivoting throughout the range of motion was lateral, the specimen was classified as a lateral pivoting dominant knee; if less than 50% was lateral, the specimen was classified as medial pivoting dominant (Fig. 4 B). Last, the total travel of the medial and lateral femoral condyles on the tibial plateau was measured by calculating the absolute sum of displacements between every consecutive knee flexion angles across the full range of motion for each specimen. To account for variations in specimen’s joint size, we normalized these translations to the size of each specimen's respective tibial plateau, with medial condyle displacements adjusted to the medial plateau size and lateral condyle displacements to the lateral plateau size. The total travel was measured for each specimen to assess the variability and magnitude of femoral condylar translations on both the medial and lateral tibial plateaus. (Fig. 4 C). Statistical Analysis The ICOR (outcome variable) was transformed into a binary classification, where “1” was defined as a lateral pivot and “0” as a medial pivot for each flexion angle. The predictor variables aHKA, JLO, and knee flexion were centered and standardized to ensure comparability of scales and improve model convergence. A generalized linear mixed-effects model was used to estimate the likelihood of lateral pivot motion, specifically in specimens classified as CPAK type III. Furthermore, the model used a binomial distribution with a logit link function for the binary outcomes. The model included aHKA, JLO, and knee flexion as fixed effects to capture their direct impact on lateral pivot behavior. To account for the inter-specimen variability, random slope, and random intercept were included as knee flexion and specimen IDs, respectively. All statistical analyses were performed in R (R-Studio Version 1.0.143, Boston, MA, USA) and the significance level was determined at p < 0.05. Results CPAK Phenotyping From the fifty-nine specimens without signs of pathology (n = 59), the most dominant CPAK types were type II (n = 28, 46.67%) and type III (n = 17, 28.33%). Type I was the third most common (n = 9, 15%), followed by type V (n = 4, 6.67%) and type VI (n = 2, 3.33%). Type IV, VII, VIII, and IX were not detected within this cohort (Fig. 3 ). Within CPAK type III, 76.5% of the data demonstrated an aHKA between 2° and 4°, while JLO ranged between 170° and 177°. The mean aHKA and JLO of the CPAK type III group measured 3.59° (standard deviation (S.D.) = ± 1.35°) and 173.2° (S.D. = ± 1.7°), respectively. Medial versus Lateral Pivoting Throughout Squatting The density plot for CPAK type III knees exhibited a bimodal pattern, showing a medial pivoting motion up to mid-flexion, which then shifted to a lateral pivoting motion from mid-flexion to deep flexion (Fig. 4 A). Each of the 17 CPAK type III knees exhibited a lateral center of rotation (lateral pivot) during squatting, whereas for 8 of these 17 lateral pivoting was the predominant pattern, extending over more than half of the flexion range (Fig. 4 B). Furthermore, the likelihood of observing lateral pivot motion, across all subjects and knee flexion angles, was 48.1%. Among the specimens, the proportion of lateral pivoting motion across the entire range of knee flexion varied from 9.23–100%, with a mean ± S.D. of 48 ± 27.62% (Fig. 4 B). Additionally, throughout the full range of knee flexion, the medial femoral condyle showed a total translation ranging between 0.05 and 0.41 across specimens (mean ± S.D. = 0.16 ± 0.1). Similarly, the lateral femoral condyle demonstrated a translation ranging from 0.06 to 0.50 (mean ± S.D. = 0.17 ± 0.1), (Fig. 4 B). The GLM model demonstrated that the effects of aHKA (p = 0.922) and JLO (p = 0.833) on lateral pivot motion were not statistically significant. Nevertheless, the knee flexion angle exhibited a significant impact (p = 0.024), showing that increased flexion was associated with a higher occurrence of lateral pivoting. Overall, lateral pivoting predominantly occurred when the knee flexion angle was ≥ 58.5° (Fig. 4 A). Discussion To the best of our knowledge, this was the first study to assess the relationship between pivoting motion and the CPAK phenotypes, more specifically type III. The main finding of this study was that all CPAK type III specimens exhibited a lateral center of rotation (lateral pivot) during loaded squatting and primarily occurring from mid to deep flexion. These results thus align with our hypothesis that the weight-bearing squatting motion is associated with lateral pivot motion in the CPAK type III knees. At first sight, our finding conflicts with prior research that identified a medial pivoting motion as the main kinematic pattern throughout flexion of the native knee joint 8 . Although medial pivot motion has indeed been observed in non-weight-bearing passive flexion of the knee 16 , 30 as well as weight-bearing squat exercises 31 – 33 , it is critical to mention that none of these studies explicitly references their findings to the lower extremity alignment. One possible explanation for the consistent reports of medial pivot could be that these studies were biased by the higher incidence of constitutional varus knees, leading to the lateral pivot seen in valgus knees, such as in CPAK III, being either underrepresented or not observed 11 , 34 . The term “lateral pivot motion” itself is not new and has been reported in the past. As mentioned above, more recent investigations of native knee kinematics have revealed that earlier stages of knee flexion associated with activities like walking, running, or pivoting are characterized by a lateral pivot pattern 20 , 21 , 24 . On the other hand, to the best of our knowledge, there are no systematic reports of such lateral pivot motion in deep flexion. Engel et al. reported that 8 out of 9 cadaveric knees showed a medial center of rotation during squatting, whereas 1 knee showed a lateral center of rotation 19 . Also, Komistek et al. described a fluoroscopic in vivo study in which the majority of 5 native knees showed medial pivoting, but one knee showed a lateral pivot motion in gait and deeper flexion 35 . Whether these lateral pivoting knees demonstrated valgus alignment unfortunately remains unknown for both studies, but is highly probable given the distribution of the Caucasian population in terms of lower extremity alignment 11 . Nevertheless, these studies do indicate that pivoting of the knee joint might be more complex than previously thought. Importantly, the bimodal pattern we observed in our study, characterized by a shift from medial to lateral pivoting for increasing flexion (see Fig. 4 A) adds to this complexity. Hence, the systematic integration of lower extremity alignment and its phenotypes in knee kinematic studies, as done in this study, has the potential to unravel this complexity. Interestingly, a very recent investigation in the correlation between knee alignment phenotypes and cartilage degeneration also suggests that a more detailed analysis of limb axis deformities should complement the assessment of cartilage and planning of an intervention 36 . Although this study was not based on CPAK, this study did highlight that, in addition to the general trend of valgus alignment being linked to lateral wear, tibial valgus is associated with medial cartilage degeneration 36 . Although the mechanistic interaction between cartilage wear and pivoting motion requires further research, the combined occurrence of medial and lateral wear thus seems to align with the bimodal pivoting pattern throughout flexion we observed in our study. Furthermore, this study indicated that the combination of a valgus femur with varus tibia phenotypes, as present in CPAK’s type III phenotypes, exhibited a strong, atypical correlation with the anterior lateral tibial subregion which importantly aligns with our finding of lateral pivoting as the main kinematic pattern and the underlying assumption of a primarily lateral transfer of tibiofemoral contact forces. Another potential confounder to consider when discussing the native knee’s pivoting behavior is the inclusion of weight- or non-weight-bearing kinematics as it is well-known that the weight-bearing kinematics differ from the non-weight-bearing 37 , 38 . Interestingly, a complementary kinematic analysis of this study’s cohort of valgus-aligned CPAK Type III specimens during passive flexion-extension did not reveal any lateral pivoting motion (See Supplementary Information). One potential reason for the differing pivot motion observed during squatting and passive flexion-extension in a valgus knee might be the way tibiofemoral contact forces are distributed between the knee’s medial and lateral compartments while bearing weight. Lerner et al. have observed that aligning the knee joint to the valgus position results in increased contact pressure at the lateral joint surface and shifts in the contact point locations 18 . Furthermore, this redistribution of contact forces, and hence also the lateral pivoting we observed, aligns with valgus alignment being a commonly accepted cause of lateral compartment wear 36 . Finally, the absence of any co-contraction in passive flexion further contributes to this differing pivot motion 38 . Our finding that native CPAK type III specimens exhibit a lateral center of rotation (lateral pivot) during squatting also has important clinical relevance. Indeed, as patient satisfaction is assumed to be correlated with TKA’s ability to restore kinematics more closely to the native knee 6 , 7 , these results provide a first indication for the clinical potential of implants that allow for a lateral pivot motion during weight-bearing motor tasks that involve deep flexion such as squatting, sit-stand-sit, or stair ascending and descending tasks. In this context, clinical results of a dual pivot TKA design have been recently reported 39 . However, the lateral pivot motion of this implant design is induced only in earlier stages of the flexion and not during deep flexion. Furthermore, the relationship between the clinical outcome of this implant and alignment phenotypes was not analysed. Hence, the proportion within their cohort of CPAK Type III subjects potentially showing native lateral pivoting remains unknown. Iwakiri et al. (40) analysed the clinical outcome of medial pivot TKA in the valgus knee. Although clinical outcomes were reported to be similar as in the varus knee, the number of valgus cases was small and underpowered. Therefore, the current literature remains inconclusive as to which implant design best fits the valgus knee. Furthermore, valgus knees still present with additional surgical challenges that might affect post-TKA kinematics 41 , including but not limited to the definition of alignment targets in constitutional valgus phenotypes such as CPAK III. Lastly, also the substantial specimen-to-specimen variation in the proportion of lateral pivoting throughout the flexion range complicates the design optimization for valgus knees. Furthermore, our results indicate that this variation cannot be attributed to alignment features of the CPAK classification as JLO and aHKA had no significant impact on the occurrence of lateral pivoting. Nevertheless, we believe the current study offers important data and insights to be considered for subsequent research on the role of native valgus knee kinematics in the optimization of TKA outcomes. Several methodological aspects of this study require further discussion. First, the CPAK classification was originally designed to be conducted by means of two-dimensional (2D) full-length lower limb standing radiograph 10 , because of its wide clinical availability. Nevertheless, accurate evaluation of the inherently three-dimensional (3D) lower limb alignment with 2D medical imaging is at risk of being confounded by lower limb rotation and flexion contractures 42 . Therefore, recent studies suggested the use of three-dimensional (3D) CT 13 , 14 and reported that 3D CT measurements of MPTA and LDFA were more reproducible and had a good correlation with two-dimensional measurements 43 . However, one of the recurrent challenges in 3D CT measurement is that the 3D definition of the tibial joint line varies throughout the literature, and consensus yet has to be reached. Fürmetz et al. defined the joint line as the line connecting the medial and lateral most cranial points on the tibial plateau 44 . Ho et al. 45 reported the best matching surfaces for the medial and lateral sides of the proximal tibia, and Micicoi et al. 46 similarly specified 35 points and used a plane that coincided with the articular surface. León-Muñoz et al. 47 and Gieroba et al. 43 used the deepest points of the tibial plateau, as in the present study. Given the complex morphology of the tibiofemoral joint, the deepest point was considered a more accurate and reproducible measurement method 43 . Secondly, our 3D CT-based analysis was non-weight-bearing in contrast with the original CPAK classification methodology. However, prior research from our group identified that deformity increases with loading 48 . Therefore, our selection of CPAK type III phenotypes was likely overly conservative, which further adds to the strength of our study. Nevertheless, further research on CPAK classification with 3D, weight-bearing measurements is warranted. Secondly, our kinematic analysis was based on the geometric center axis of the distal femur (GCA). More specifically, spheres that fit the flexion facets of the medial and lateral posterior condyles (FMCC and FLCC) were used to define the GCA 26 , 49 , 50 . This GCA was then projected onto the tibial plane to evaluate anteroposterior condyle translations and, hence, identify the pivoting motion of the knee 49 . Nevertheless, other studies relied on the trans-epicondylar axis (TEA). Although both have been extensively used in past studies 51 , 52 , it has been reported that the choice between both can affect the identification of kinematic patterns underlying a given knee movement 50 . Rao et al. advocated that, without considering the intricate patterns of knee motion along the flexion path, the TEA may oversimplify the fundamental link between the anatomy and kinematics of the knee 53 . Mochizuki et al. also stated that the TEA was not a good surrogate for the functional flexion axis 54 . Based on these studies, we preferred GCA over TEA. Other possible kinematic analysis approaches include contact estimates, lowest point kinematics, and functional axes 55 , 56 . However, there is still controversy as to which method is the most appropriate, warranting further research. Thirdly, specimens considered to have severe OA were excluded from this study. The primary motivation behind this was that this study targeted the identification of native kinematics. According to Hamai et al., patients with medial OA have different weight-bearing kinematics than native knees 57 . Furthermore, it is well known that anterior cruciate ligament (ACL) dysfunction has a coherent relationship with OA 58 – 60 . Murayama et al. reported that the motion pattern of ACL dysfunctional knees was different from that of the contralateral, healthy knees 32 . Dennis et al. also found that the center of rotation of normal and ACL dysfunctional subjects differ significantly 33 . Based on these studies, we aimed to prevent our conclusions from being affected by (1) changes in joint surface shape due to severe OA and/or (2) ACL dysfunction due to severe OA. Fourthly, this study made use of a physiological ex vivo knee simulator to mimic the native function of the knee joint. Alternatively, intraoperative navigation systems have been used to assess knee kinematics during surgery 16 , 17 , 25 . However, this method only allows the assessment of passive knee function in a non-weight-bearing state. Alternatively, in vivo analysis using fluoroscopy is often performed 20 , 24 , 31 – 33 , 35 , 50 , 51 , 54 , 57 , 61 , but this has the disadvantage of exposing the subject to high levels of radiation, in addition to practical and financial constraints. Moreover, it is also known that there are limitations to the accuracy of reproduction of natural activity 36 . In other words, natural, unrestricted motion, such as squatting, is difficult to analyse in larger cohorts given the specific constraints of fluoroscopes. On the other hand, the use of a physiological ex vivo knee simulator is an alternative complementary assessment method that mimics the weight-bearing situations while applying physiological muscle loads, which is not limited to ethical, time, and practical constraints compared to in vivo testing 19 , 62 , 63 . The simulator used in this study, and hence the uniquely large cohort of specimens analysed with it, has been proven reliable and useful in previous studies 62 – 64 . Nevertheless, this study has several remaining limitations. First, despite prior studies documenting the representativeness of such cadaveric simulations for in vivo knee function 65 , care should still be taken when extrapolating these findings to in vivo knee joint kinematics during a wider range of daily life motor tasks. Secondly, this study only investigated pivoting motion within knee flexion ranging from 35 to 100°. Therefore, the pivoting behaviour in extension and early flexion could not be investigated. Thirdly, our study used a simplified definition of medial and lateral pivoting compared to more detailed or restricted approaches reported in the literature. Previous studies have used methods such as the mean of overall pivoting to identify the center of rotation 66 or categorized motion into distinct types—no pivot, medial pivot, lateral pivot, and central pivot—over the knee flexion angle 67 . In contrast, we assessed pivoting throughout the entire range of motion without focusing on a single mean or restricting to specific definitions. Fourthly, we did not analyse the influence of patellar tracking, which might be a contributing factor for the lateral pivoting. The patella fits into the trochlear groove during flexion, affecting the pressure on the tibiofemoral joint 68 , 69 . However, it remains unclear how patella alignment affects pivot motion 70 . Further studies are required for understanding the relationship between the patellar tracking and pivot motion. Finally, our findings are based on a limited sample of only 17 CPAK type III knees and may not be representative of the entire population with valgus alignment, especially the cases with a higher aHKA or lower JLO. Conclusion This study analysed the relationship between pivot motion during squatting and lower extremity valgus alignment (CPAK classification) and showed that a lateral pivot motion pattern occurred during squatting in approximately half of CPAK type III specimens from mid to deep flexion when tested in a loaded knee simulator. The current study offers essential data and insights to be considered for subsequent research on the role of native valgus knee kinematics in optimizing TKA outcomes. Declarations Data availability statement The datasets generated and/or analysed during the current study are not publicly available due to ethical restrictions, as the data were obtained from previously tested human donor specimens. Access to the data is available from the corresponding author upon reasonable request and subject to approval by the senior author and their affiliated university. The source data from which the results were generated and analysed are included in the Supplementary Information document. Contributions G.P. drafted the first manuscript of this article, coordinated the manuscript with all co-authors, supervised all aspects, interpreted the results and revised manuscript sections. O.T. collected measurements, developed the code for data processing, post-processed all data, and analysed the results, drafted the first manuscript of this article, coordinated the manuscript with all co-authors recruited participants, revised manuscript sections. J.I. and G.P. post-processed some of the data, analysed the results, and drafted the first manuscript of this article. J.B. developed the research agenda behind this work, revised manuscript sections and supervised all aspects. L.S. collected measurements, developed the research agenda behind this work, interpreted the results, revised manuscript sections and supervised all aspects. All authors contributed to the study design, interpreted the results, wrote and revised manuscript sections, read and approved the submitted version. Use of human tissue samples This study involved only previously collected data from cadaveric human donor specimens, which were originally tested as part of earlier ethically approved studies. No new experiments involving human participants or the collection of human tissue were conducted for this study. All methods utilized in the original studies received approval from the Local KU Leuven Ethics Committee in accordance with relevant guidelines and regulations. Due to the retrospective nature of the study, the Local KU Leuven Ethics Committee waived the need of obtaining informed consent. Competing interests The authors declare declare no potential conflict of interest. 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Knee Surg. 32 , 590–595 (2019). Howell, S. M., Akhtar, M., Nedopil, A. J. & Hull, M. L. Reoperation, implant survival, and clinical outcome after kinematically aligned total knee arthroplasty: A concise clinical follow-up at 16 years. J. Arthroplasty 39 , 695–700 (2024). Freeman, M. A. & Pinskerova, V. The movement of the knee studied by magnetic resonance imaging. Clin. Orthop. Relat. Res. 410 , 35–43 (2003). Iida, T. et al. Mid-term clinical results of alumina medial pivot total knee arthroplasty. Knee Surg. Sports Traumatol. Arthrosc. 20 , 1514–1519 (2012). MacDessi, S. J., Jones, W. G., Harris, I. A., Bellemans, J. & Chen, D. B. Coronal plane alignment of the knee (CPAK) classification: a new system for describing knee phenotypes. Bone Joint J. 103B , 329–337 (2023). Pagan, C. A. et al. Geographic variation in knee phenotypes based on the coronal plane alignment of the knee classification: a systematic review. J. Arthroplasty. 38 , 1892–1899 (2023). 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Batra, S., Sugumar, P. A. A., Kumar, V. & Malhotra, R. Which one restores in vivo knee kinematics effectively—medial or lateral pivot? J. Clin. Orthop. Trauma 13 , 70–73 (2021). Yamaguchi, S. et al. In vivo kinematics of anterior cruciate ligament deficient knees during pivot and squat activities. Clin. Biomech. (Bristol, Avon) 24 , 71–76 (2009). Hoshino, Y. & Tashman, S. Internal tibial rotation during in vivo, dynamic activity induces greater sliding of tibio-femoral joint contact on the medial compartment. Knee Surg. Sports Traumatol. Arthrosc. 20 , 1268–1275 (2012). Meneghini, R. M., Deckard, E. R., Ishmael, M. K. & Ziemba-Davis, M. A dual-pivot pattern simulating native knee kinematics optimizes functional outcomes after total knee arthroplasty. J. Arthroplasty 32 , 3009–3015 (2017). Victor, J., Van Glabbeek, F., Vander Sloten, J., Parizel, P. M., Somville, J. & Bellemans, J. An experimental model for kinematic analysis of the knee. J. Bone Joint Surg. Am. 91 , 150–163 (2009). Victor, J., Van Doninck, D., Labey, L., Innocenti, B., Parizel, P. M. & Bellemans, J. How precise can bony landmarks be determined on a CT scan of the knee? Knee 16 , 358–365 (2009). Grood, E. S. & Suntay, W. J. A joint coordinate system for the clinical description of three-dimensional motions: application to the knee. J. Biomech. Eng. 105 , 136–144 (1983). Tarassoli, P. et al. Arithmetic hip-knee-ankle angle and stressed hip-knee-ankle angle: equivalent methods for estimating constitutional lower limb alignment in kinematically aligned total knee arthroplasty. Knee Surg. Sports Traumatol. Arthrosc. 30 , 2980–2990 (2022). Freeman, M. A. & Pinskerova, V. The movement of the normal tibio-femoral joint. J. Biomech. 38 , 197–208 (2005). Moro-oka, T. A. et al. Dynamic activity dependence of in vivo normal knee kinematics. J. Orthop. Res. 26 , 428–434 (2008). Murayama, T. et al. Three-dimensional in vivo dynamic motion analysis of anterior cruciate ligament-deficient knees during squatting using geometric center axis of the femur. J. Orthop. Sci. 21 , 159–165 (2016). Dennis, D. A., Mahfouz, M. R., Komistek, R. D. & Hoff, W. In vivo determination of normal and anterior cruciate ligament-deficient knee kinematics. J. Biomech. 38 , 241–253 (2005). Bellemans, J., Colyn, W., Vandenneucker, H. & Victor, J. The Chitranjan Ranawat award: is neutral mechanical alignment normal for all patients? The concept of constitutional varus. Clin. Orthop. Relat. Res. 470 , 45–53 (2012). Komistek, R. D., Dennis, D. A. & Mahfouz, M. In vivo fluoroscopic analysis of the normal human knee. Clin. Orthop. Relat. Res. 410 , 69–81 (2003). Khury, F. et al. Which knee phenotypes exhibit the strongest correlation with cartilage degeneration? Clin. Orthop. Relat. Res. 482 , 500–510 (2024). Johal, P., Williams, A., Wragg, P., Hunt, D. & Gedroyc, W. Tibio-femoral movement in the living knee. A study of weight bearing and non-weight bearing knee kinematics using ‘interventional’ MRI. J. Biomech. 38 , 269–276 (2005). Victor, J., Labey, L., Wong, P., Innocenti, B. & Bellemans, J. The influence of muscle load on tibiofemoral knee kinematics. J. Orthop. Res. 28 , 419–428 (2010). Sandberg, R., Deckard, E. R., Ziemba-Davis, M., Banks, S. A. & Meneghini, R. M. Dual-pivot bearings improve ambulation and promote increased activity levels in total knee arthroplasty: A match-controlled retrospective study. Knee 26 , 1243–1249 (2019). Iwakiri, K. et al. Is medial pivot total knee arthroplasty suitable for patients with valgus knee osteoarthritis? Eur. J. Orthop. Surg. Traumatol. 32 , 551–557 (2022). Alesi, D. et al. Total knee arthroplasty in valgus knee deformity: is it still a challenge in 2021? Musculoskelet. Surg. 106 , 1–8 (2022). Lazennec, J. Y. et al. Are advanced three-dimensional imaging studies always needed to measure the coronal knee alignment of the lower extremity? Int. Orthop. 41 , 917–924 (2017). Gieroba, T. J., Marasco, S., Babazadeh, S., Di Bella, C. & van Bavel, D. Arithmetic hip-knee angle measurement on long leg radiograph versus computed tomography—inter-observer and intra-observer reliability. Arthroplasty 5 , 35 (2023). Furmetz, J. et al. Three-dimensional assessment of lower limb alignment: Accuracy and reliability. Knee. 26 , 185–193 (2019). Ho, J. P. Y. et al. Tibia vara in Asians: Myth or fact? Verification with three-dimensional computed tomography. J. Orthop. Surg. (Hong Kong) 29 , (2021). Micicoi, G. et al. Neutral alignment resulting from tibial vara and opposite femoral valgus is the main morphologic pattern in healthy middle-aged patients: an exploration of a 3D-CT database. Knee Surg. Sports Traumatol. Arthrosc. 29 , 849–858 (2021). Leon-Munoz, V. J., Lopez-Lopez, M., Martinez-Martinez, F. & Santonja-Medina, F. Comparison of weight-bearing full-length radiographs and computed-tomography-scan-based three-dimensional models in the assessment of knee joint coronal alignment. Knee 27 , 543–551 (2020). Colyn, W., Vanbecelaere, L., Bruckers, L., Scheys, L. & Bellemans, J. The effect of weight-bearing positions on coronal lower limb alignment: A systematic review. Knee 43 , 51–61 (2023). Victor, J. et al. A common reference frame for describing rotation of the distal femur: A CT-based kinematic study using cadavers. J. Bone Joint Surg. Br. 91 , 683–690 (2009). Tanifuji, O. et al. Three-dimensional in vivo motion analysis of normal knees employing transepicondylar axis as an evaluation parameter. Knee Surg. Sports Traumatol. Arthrosc. 21 , 2301–2308 (2012). Li, G., Zhou, C., Zhang, Z., Foster, T. & Bedair, H. Articulation of the femoral condyle during knee flexion. J. Biomech. 131 , 110906 (2022). Ren, L. et al. Identifying the functional flexion-extension axis of the knee: An in vivo kinematics study. PLoS One 10 , e0129631 (2015). Rao, Z. et al. There are isoheight points that measure constant femoral condyle heights along the knee flexion path. Knee Surg. Sports Traumatol. Arthrosc. 29 , 600–607 (2021). Mochizuki, T. et al. The clinical epicondylar axis is not the functional flexion axis of the human knee. J. Orthop. Sci. 19 , 451–456 (2014). Postolka, B. et al. . Interpretation of natural tibio-femoral kinematics critically depends upon the kinematic analysis approach: A survey and comparison of methodologies. J. Biomech. 144 , 111306 (2022). Hamilton, L. D., Shelburne, K. B., Rullkoetter, P. J., Barnes, C. L. & Mannen, E. M. Kinematic performance of medial pivot total knee arthroplasty. J. Arthroplasty. 39 , 1595–1601 (2023). Hamai, S. et al . Knee kinematics in medial osteoarthritis during in vivo weight-bearing activities. J. Orthop. Res. 27 , 1555–1561 (2009). Waldstein, W., Merle, C., Monsef, J. B. & Boettner, F. Varus knee osteoarthritis: how can we identify ACL insufficiency? Knee Surg. Sports Traumatol. Arthrosc. 23 , 2178–2184 (2015). Hasegawa, A. et al. Anterior cruciate ligament changes in the human knee joint in aging and osteoarthritis. Arthritis Rheum. 64 , 696–704 (2012). Weston-Simons, J. S. et al. Outcome of combined unicompartmental knee replacement and combined or sequential anterior cruciate ligament reconstruction. J. Bone Joint Surg. Br. 94B , 1216–1220 (2012). Murakami, K. et al. Knee kinematics in bi-cruciate stabilized total knee arthroplasty during squatting and stair-climbing activities. J. Orthop. 15 , 650–654 (2018). Heyse, T. J. et al. Kinematics of a bicruciate-retaining total knee arthroplasty. Knee Surg. Sports Traumatol. Arthrosc. 25 , 1784–1791 (2017). Peersman, G. et al. Kinematics of mobile-bearing unicompartmental knee arthroplasty compared to native: results from an in vitro study. Arch. Orthop. Trauma Surg. 137 , 1557–1563 (2017). Ghijselings, I. et al. Using a patella reduced technique while balancing a TKA results in restored physiological strain in the collateral ligaments: an ex vivo kinematic analysis. Arch. Orthop. Trauma Surg. 142 , 1633–1644 (2022). Peersman, G. et al. Does unicondylar knee arthroplasty affect tibial bone strain? A paired cadaveric comparison of fixed- and mobile-bearing designs. Clin. Orthop. Relat. Res. 478 , 1990–2000 (2020). Postolka, B., Taylor, W. R., Fucentese, S. F., List, R. & Schutz, P. The role of limb alignment on natural tibiofemoral kinematics and kinetics. Bone Joint Res. 13 , 485–496 (2024). Hamilton, L. D. et al. Knee pivot location in asymptomatic older adults. J. Biomech. 149 , 111487 (2023). Chinzei, N. et al. Evaluation of patellofemoral joint in ADVANCE medial-pivot total knee arthroplasty. Int. Orthop. 38 , 509–515 (2014). Matsumoto, T. et al. Joint gap kinematics in posterior-stabilized total knee arthroplasty measured by a new tensor with the navigation system. J. Biomech. Eng. 128 , 867–871 (2006). Konno, T. et al. Correlation between knee kinematics and patellofemoral contact pressure in total knee arthroplasty. J. Arthroplasty 29 , 2305–2308 (2014). Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformation.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6385860","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":492867308,"identity":"dae61c98-bf58-4c4b-86bf-5bc29b1ad892","order_by":0,"name":"Geert Peersman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYAgAGxDBRljdAQQzjXQthwlrkXdvPvb5A8MdOX7p4083/Nxx3p6//wDbgw94tBieOZY84wDDM2PJvhyzm71nbjNL3EhgN5yBT8uMHGOgww4nbjjDw3aDt+02G8MNBjZpHnxa5r//DNJSv/8M+7Obf9vO8cifP8Am/QefXyR4mEFaEgx4GMxu87YdkDA4kMAmjc/7BjxpxgxnDJ4ZzjjDY3Zbti3ZwPBGYrthDz5b2g8/ZqiouCPP3wN02Ns2O3u584ePPfiBz5YDCBIGGBvwuYtBHiJ9AK+iUTAKRsEoGOEAAErkUJoFfNNuAAAAAElFTkSuQmCC","orcid":"","institution":"Ziekenhuis Netwerk Antwerpen Cadix","correspondingAuthor":true,"prefix":"","firstName":"Geert","middleName":"","lastName":"Peersman","suffix":""},{"id":492867309,"identity":"fe85b7c6-efaa-488b-bec3-b3a17465b824","order_by":1,"name":"Orçun Taylan","email":"","orcid":"","institution":"Institute for Orthopaedic Research and Training (IORT), KU Leuven","correspondingAuthor":false,"prefix":"","firstName":"Orçun","middleName":"","lastName":"Taylan","suffix":""},{"id":492867310,"identity":"222583b8-a419-4797-9697-613059d82d19","order_by":2,"name":"Junya Itou","email":"","orcid":"","institution":"Ziekenhuis Netwerk Antwerpen Cadix","correspondingAuthor":false,"prefix":"","firstName":"Junya","middleName":"","lastName":"Itou","suffix":""},{"id":492867311,"identity":"ecb53987-3cd1-40ea-901e-2335e70c5a83","order_by":3,"name":"Gérard Peersman","email":"","orcid":"","institution":"Institute for Orthopaedic Research and Training (IORT), KU Leuven","correspondingAuthor":false,"prefix":"","firstName":"Gérard","middleName":"","lastName":"Peersman","suffix":""},{"id":492867312,"identity":"b974a098-f59d-44e3-b93a-ab0ae2c8b253","order_by":4,"name":"Johan Bellemans","email":"","orcid":"","institution":"Institute for Orthopaedic Research and Training (IORT), KU Leuven","correspondingAuthor":false,"prefix":"","firstName":"Johan","middleName":"","lastName":"Bellemans","suffix":""},{"id":492867313,"identity":"f6ed8a6d-94f2-4af2-bf7d-e188ce5708c3","order_by":5,"name":"Lennart Scheys","email":"","orcid":"","institution":"Institute for Orthopaedic Research and Training (IORT), KU Leuven","correspondingAuthor":false,"prefix":"","firstName":"Lennart","middleName":"","lastName":"Scheys","suffix":""}],"badges":[],"createdAt":"2025-04-06 09:23:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6385860/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6385860/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88038665,"identity":"05e530e3-aaea-4c1d-a6ab-e0f8f38d1d17","added_by":"auto","created_at":"2025-07-31 16:40:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":509184,"visible":true,"origin":"","legend":"\u003cp\u003eOverview of testing protocol\u003c/p\u003e\n\u003cp\u003e(a) Specimen preparation and computed-tomography imaging, (b) anatomical landmark and reflective markers identification and each bone’s coordinate system identification, (c) the lateral distal femoral angle (LDFA) and the proximal tibial angle (MPTA) measurement in 3D using each bone’s coronal view and (d) squatting motion in Oxford-based physiological cadaver knee simulator.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6385860/v1/fcdb0aaf5747dea96236dbeb.png"},{"id":88036963,"identity":"593e474e-3123-41e1-a6ea-6d5c8e42ddf1","added_by":"auto","created_at":"2025-07-31 16:24:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":254921,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of femoral rollback pattern\u003c/p\u003e\n\u003cp\u003eSolid black dots represent the respective centers of the medial and lateral femoral condyles projected on the tibia plateau. The asterisk (*) with gradient colors shows the instantaneous center of rotation (ICOR) calculated from each consecutive pair of knee flexion angles throughout the squatting motion from the extension (35°, black) to flexion (100°, yellow). Negative values indicate the medial and posterior regions, while positive values indicate the lateral and anterior regions.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6385860/v1/13ec48abf0150b30118ab925.png"},{"id":88036952,"identity":"8bb17fd3-49a3-411b-b836-7acee0dbac2f","added_by":"auto","created_at":"2025-07-31 16:24:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":89979,"visible":true,"origin":"","legend":"\u003cp\u003eCPAK distribution\u003c/p\u003e\n\u003cp\u003eDistribution of arithmetic hip-knee-ankle angle (aHKA) plotted against joint line obliquity obtained from fifty-nine (n = 59) specimens, illustrating distribution by percentage in the nine Coronal Plane Alignment of the Knee (CPAK) types. MPTA = medial proximal tibial angle; LDFA = lateral distal femoral angle\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6385860/v1/ff147621c4ee543d98e49cbc.png"},{"id":88036955,"identity":"31197deb-305b-4e46-9f51-656be1faef8d","added_by":"auto","created_at":"2025-07-31 16:24:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":130033,"visible":true,"origin":"","legend":"\u003cp\u003ePivoting motion for CPAK Type III specimens during squatting\u003c/p\u003e\n\u003cp\u003e(A) Density plot of the instantaneous center of rotation (ICOR) for all CPAK type III specimens throughout the full squatting motion (35°–100°), with density represented by a color gradient from white (low density) to dark blue (high density). (B) Proportion (%) of the flexion range of motion (ROM) demonstrating lateral pivoting for the cohort of CPAK type III specimens (n=17). The specimens are ordered from minimum to maximum aHKA values. (C) Total anterior-posterior travel of the medial and lateral femur condyles projected on the tibial plateau. Total travel was defined as the summation of the travel between every consecutive knee flexion angle across the range of motion for each specimen, calculated separately in absolute terms for both the medial and lateral translations. The red dashed line indicates equal proportions for (a) and (b), respectively. Both the ICOR and total travel data are normalized to the size of each specimen’s tibial plateau. The specimens are ordered from minimum to maximum aHKA values.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6385860/v1/9d775eca7ac7ae2f84b37c30.png"},{"id":89457713,"identity":"0ca87a22-2d03-4a65-b318-e2c8ab149da6","added_by":"auto","created_at":"2025-08-20 07:16:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1738040,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6385860/v1/f8e59b08-4ada-4eaa-9b1b-701785a15fac.pdf"},{"id":88036949,"identity":"11289add-1362-43e8-a7a7-b6f075d60991","added_by":"auto","created_at":"2025-07-31 16:24:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1790642,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6385860/v1/d3f1079206cbf3c62b76dcc7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Coronal Plane Alignment Of The Knee (CPAK) Type III Valgus Knee Exhibits Lateral Pivot Motion During Squatting","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTotal knee arthroplasty (TKA) is considered the gold standard treatment for relieving pain and restoring knee function in patients with knee osteoarthritis (OA)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Unfortunately, it is also true that not everyone who has undergone TKA is satisfied\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Although the exact reasons for this may be diverse, it could be assumed that patient satisfaction is correlated with the TKA\u0026rsquo;s ability to restore kinematics more closely to the native knee\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Hence, understanding native knee kinematics and its phenotypes is warranted to further improve clinical outcomes and patient satisfaction.\u003c/p\u003e\u003cp\u003ePrior research has identified a medial pivoting motion as the main kinematic pattern throughout flexion of the native knee joint\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Based hereon, medial pivot-type prosthesis designs have been introduced to restore preoperative kinematics and, indeed, excellent clinical outcomes have been reported for varus knees\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Recently, the coronal plane alignment of the knee (CPAK) classification was introduced by MacDessi et al.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e which categorizes all knees into nine alignment-based phenotypes and is intended to enhance TKA planning with the patient\u0026rsquo;s constitutional limb alignment in mind. Furthermore, CPAK types I and II, i.e. varus knees, were reported to be the most common phenotype in both healthy and arthritic populations, whereas only 2.4\u0026ndash;28.4% have been classified as CPAK types III, VI or IX, i.e. valgus knees\u003csup\u003e\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Nevertheless, the association between these alignment-based phenotypes and their respective kinematic behavior has not been adequately evaluated. Indeed, prior studies documenting native knee kinematics did not base their evaluation of lower extremity alignment yet on alignment-phenotypes such as the CPAK classification. As a result, the identification of medial pivoting as the main kinematic pattern might have been biased by the more common varus-aligned phenotypes and its applicability to the less common valgus-aligned phenotypes thus remains to be confirmed.\u003c/p\u003e\u003cp\u003eWithin this context, prior research did already establish that knees with varus and valgus deformities exhibit different kinematic patterns\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Some authors have suggested that these differences may be primarily associated with the varying alignment of the lower-limbs weight-bearing axis leading to a more medial tibiofemoral contact point in varus knees versus a more lateral contact point in valgus knees\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Indeed, in contrast to the traditional belief that knees solely exhibit a medial pivoting kinematic behavior\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, more recent studies have reported a more variable pivoting behavior throughout the full knee range of motion\u003csup\u003e\u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. For example, Meneghini et al. have stated that during activities of daily living, such as walking, running, or pivoting the native knee exhibits a lateral pivot pattern in earlier knee flexion, whereas medial pivoting occurred during deeper knee flexion\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. However, also here the association between native knee kinematics and CPAK\u0026rsquo;s phenotypes was not documented.\u003c/p\u003e\u003cp\u003eOur current understanding of how native weight-bearing kinematics are related to an individual\u0026rsquo;s constitutional alignment as expressed in the CPAK classification, remains to be fully investigated, specifically in terms of its pivoting motion in the less common valgus phenotypes. Gaining insight into the pivoting motion patterns, especially in the valgus knees, may greatly help surgeons determine an optimal treatment strategy. Moreover, its restoration in TKA may, in theory, result in better patient outcomes and increased patient satisfaction. Therefore, this study aimed to perform a detailed analysis of the pivoting motion of CPAK type III knees as the most common valgus phenotype\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, during \u003cem\u003eex vivo\u003c/em\u003e simulated squatting. Considering the more lateral weight-bearing axis in the valgus knee, it was hypothesized that the weight-bearing squatting motion could be associated with a more dominant lateral pivot motion\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eFor this study we retrospectively analysed a previously collected dataset documenting tibiofemoral kinematics of sixty-nine native fresh-frozen cadaveric knees (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) that were subjected to passive flexion and squatting motions; the latter using a single physiological \u003cem\u003eex vivo\u003c/em\u003e knee simulator, between 2014 and 2023. All specimens were tested following ethical approval with a consistent, well-established method briefly outlined hereunder (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographics of the specimens, including the Coronal Plane Alignment of the Knee (CPAK) classification, number of the samples, age distribution, gender (%), height, weight, and size of the tibial plateau in anterior-posterior and medial-lateral directions.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCPAK Type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGender (Male %)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHeight\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eWeight\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMedial AP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLateral AP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eMediolateral ML\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e85\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e171.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e81.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e44.98\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e36.62\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e76.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e81.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e63.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e170.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e43.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e37.41\u0026thinsp;\u0026plusmn;\u0026thinsp;4.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e76.95\u0026thinsp;\u0026plusmn;\u0026thinsp;5.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e79.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e170.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e75.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e43.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e37.51\u0026thinsp;\u0026plusmn;\u0026thinsp;4.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e75.86\u0026thinsp;\u0026plusmn;\u0026thinsp;5.55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e81.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e179\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;17.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e45.13\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e38.41\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e78.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e79.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e171.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e77.2\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e46.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e\u003cp\u003e37.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e\u003cp\u003e79.17\u0026thinsp;\u0026plusmn;\u0026thinsp;5.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csub\u003eMedial AP = Medial tibial plateau anterior\u0026minus;posterior size (mm); Lateral AP = Lateral tibial plateau anterior\u0026minus;posterior size (mm); ML = Mediolateral size of tibial plateau (mm); the values with \u0026ldquo;\u0026plusmn;\u0026rdquo; indicate mean \u0026plusmn; standard deviation\u003c/sub\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePrior to the testing, bi-cortical bone pins were inserted into the femur and tibia to attach rigid frames containing four retroreflective spheres. Non-weight-bearing computed tomography (CT) scans were acquired from the specimens in full extension with a slice thickness of 0.6\u0026ndash;0.75 mm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e\u003cp\u003eThe CT scans and available lab notes were screened by an experienced surgeon for possible signs of severe OA (i.e. equilavent to Kellgren and Lawrence grade 3 and grade 4) or pathology that might have affected the kinematic behavior (e.g. fracture history). Based hereon, ten (n\u0026thinsp;=\u0026thinsp;10) out of the sixty-nine (n\u0026thinsp;=\u0026thinsp;69) specimens were excluded.\u003c/p\u003e\u003cp\u003eNext, segmentation software (Mimics 25.0, Materialise, Leuven, Belgium) was used to identify the location of the spherical markers, as well as specific anatomical landmarks\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e to define a joint coordinate system for the femur and tibia based on the Grood and Suntay conventions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB)\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIdentification of CPAK Type III Knees\u003c/p\u003e\u003cp\u003eEach specimen\u0026rsquo;s CT scan was imported into Mimics (Materialise, Leuven, Belgium), and 3-D models of the femur and tibia were generated. Detailed reconstructions were performed for the distal femur and proximal tibia to allow accurate definition of the required landmarks. More specifically, the following femoral and tibial anatomical landmarks were identified as described by Victor et al \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). For the femur, the mechanical axis (vertical axis) was defined by the line between the femoral hip center (FHC) and the femoral knee center (FKC). The femoral medio-lateral axis was defined by a line between the femoral medial condyle center (FMCC) and the femoral lateral condyle center (FLCC). The anterior-posterior axis of the femur was defined as the axis that is mutually perpendicular to both the mechanical axis and the medio-lateral axis of the femur. The tibial mechanical axis was defined as the line between the center of the tibial plateau (TKC) and the ankle joint (TAC). The tibial medio-lateral axis was defined by a line from the point of the medial condyle center (TMCC) to the lateral condyle center (TLCC). Consequently, the anterior-posterior axis was defined as the line mutually perpendicular to these two axes. The above vertical and medio-lateral axes definitions were then used to define the coronal plane for both the femur and tibia.\u003c/p\u003e\u003cp\u003eNext, the lateral distal femoral angle (LDFA) and the proximal tibial angle (MPTA) were calculated. The LDFA was defined as the angle on the lateral side between the femoral mechanical axis and the joint line of the distal femur\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e projected on the coronal plane (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). To define the joint line, the most distal points of the medial and the lateral femoral condyles were identified\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Similarly, the MPTA was described as the angle on the medial side between the tibia\u0026rsquo;s mechanical axis and the coronal plane projection of the joint line of the proximal tibia, defined as the line connecting the deepest points of the medial and lateral tibial plateau (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC)\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo determine the CPAK classification for each knee, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated based on the LDFA and MPTA\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Accordingly, the aHKA was calculated as the difference between MPTA and LDFA, while JLO was the sum of MPTA and LDFA. The bony landmark identification and CPAK phenotyping were performed by an experienced knee surgeon who was not involved in the experimental data collection and was blinded to the sample identifications.\u003c/p\u003e\u003cp\u003eExperimental Protocol\u003c/p\u003e\u003cp\u003eAll specimens were thawed 24 hours prior to testing, with a maximum of two freezing-thawing cycles. The femur and tibia were resected 320 mm proximal and 280 mm distal to the knee joint line, respectively. The skin and subcutaneous tissue surrounding the knee joint were carefully removed while preserving the joint capsule, ligaments and tendons. The exposed quadriceps tendon was clamped within a custom metal clamp, and suture loops (2x2 non-absorbable polyester braided suture wire; Cardioxyl, Peters Surgical, Bobigny Cedex, France) were passed through the medial and lateral hamstrings. Subsequently, the femur and tibia were embedded into metal containers using acrylic resin (Struers, Ballerup, Denmark), with the femur positioned in 6\u0026deg; of valgus.\u003c/p\u003e\u003cp\u003eEach specimen was mounted into an Oxford-based dynamic \u003cem\u003eex vivo\u003c/em\u003e knee simulator and subjected to loaded squatting (35\u0026deg; \u0026ndash; 100\u0026deg;). During squatting motion, 50 N constant force springs were attached to the medial and lateral hamstrings suture loops to apply a constant load throughout the entire flexion cycle, while the quadriceps clamp was fixed to a linear actuator. The force of the electromechanical quadriceps actuator was computer-controlled to apply physiological quadriceps load while maintaining a vertical ankle load of 110 N. Each motion was performed in triplicate, and the trajectories of the retro-reflective spheres attached to the specimens were recorded using six infrared cameras (Vicon Motion Systems, Oxford, UK) operating at 100 Hz.\u003c/p\u003e\u003cp\u003eIdentification of Medial or Lateral Pivoting Motion\u003c/p\u003e\u003cp\u003eThe trajectories of the bone-pin mounted reflective markers were reconstructed in 3D (Nexus 2.9, Vicon, Oxford, UK). Based hereon, tibiofemoral translations and rotations during squatting were computed with custom-written code in Matlab (R2018b, Mathworks Inc, Natick, MA, USA). Each kinematic variable was down-sampled and interpolated at intervals of 1\u0026deg; of flexion and within the common range of knee flexion shared by all specimens for squatting (35\u0026deg; \u0026ndash; 100\u0026deg;).\u003c/p\u003e\u003cp\u003eTo determine the instantaneous center of rotation (ICOR) during squatting, the medial-lateral axis of the femur was projected onto the transverse plane of the tibia. For each consecutive pair of knee flexion angles, the intersection points of the medial-lateral axis of the femur projected onto the tibial plateau were calculated, resulting in the ICORs as a function of knee flexion angle, as described by Koo and Andriacchi\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. These points provided a detailed pattern of how the center of rotation changed during knee flexion (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eNext, we discriminated between medial and lateral pivoting motion throughout the flexion range of squatting motion based on the medio-lateral position of the ICOR with respect to the TKC: if the ICOR was medial or lateral to the TKC, the associated flexion angle was identified as demonstrating medial or lateral pivoting, respectively.\u003c/p\u003e\u003cp\u003eFinally, a density plot was created to visualize the medio-lateral distribution of the ICORS location as a function of the flexion angle for those specimens classified as CPAK type III (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). In addition, the proportion of lateral pivoting relative to total pivoting (medial\u0026thinsp;+\u0026thinsp;lateral) was assessed for each specimen across the full range of motion (35\u0026deg; \u0026ndash; 100\u0026deg;). The percentage of lateral pivoting was calculated to further classify specimens. If more than 50% of the total pivoting throughout the range of motion was lateral, the specimen was classified as a lateral pivoting dominant knee; if less than 50% was lateral, the specimen was classified as medial pivoting dominant (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Last, the total travel of the medial and lateral femoral condyles on the tibial plateau was measured by calculating the absolute sum of displacements between every consecutive knee flexion angles across the full range of motion for each specimen. To account for variations in specimen\u0026rsquo;s joint size, we normalized these translations to the size of each specimen's respective tibial plateau, with medial condyle displacements adjusted to the medial plateau size and lateral condyle displacements to the lateral plateau size. The total travel was measured for each specimen to assess the variability and magnitude of femoral condylar translations on both the medial and lateral tibial plateaus. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eC).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eThe ICOR (outcome variable) was transformed into a binary classification, where \u0026ldquo;1\u0026rdquo; was defined as a lateral pivot and \u0026ldquo;0\u0026rdquo; as a medial pivot for each flexion angle. The predictor variables aHKA, JLO, and knee flexion were centered and standardized to ensure comparability of scales and improve model convergence.\u003c/p\u003e\u003cp\u003eA generalized linear mixed-effects model was used to estimate the likelihood of lateral pivot motion, specifically in specimens classified as CPAK type III. Furthermore, the model used a binomial distribution with a logit link function for the binary outcomes. The model included aHKA, JLO, and knee flexion as fixed effects to capture their direct impact on lateral pivot behavior. To account for the inter-specimen variability, random slope, and random intercept were included as knee flexion and specimen IDs, respectively. All statistical analyses were performed in R (R-Studio Version 1.0.143, Boston, MA, USA) and the significance level was determined at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eCPAK Phenotyping\u003c/p\u003e\u003cp\u003eFrom the fifty-nine specimens without signs of pathology (n\u0026thinsp;=\u0026thinsp;59), the most dominant CPAK types were type II (n\u0026thinsp;=\u0026thinsp;28, 46.67%) and type III (n\u0026thinsp;=\u0026thinsp;17, 28.33%). Type I was the third most common (n\u0026thinsp;=\u0026thinsp;9, 15%), followed by type V (n\u0026thinsp;=\u0026thinsp;4, 6.67%) and type VI (n\u0026thinsp;=\u0026thinsp;2, 3.33%). Type IV, VII, VIII, and IX were not detected within this cohort (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Within CPAK type III, 76.5% of the data demonstrated an aHKA between 2\u0026deg; and 4\u0026deg;, while JLO ranged between 170\u0026deg; and 177\u0026deg;. The mean aHKA and JLO of the CPAK type III group measured 3.59\u0026deg; (standard deviation (S.D.)\u0026thinsp;=\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u0026deg;) and 173.2\u0026deg; (S.D. = \u0026plusmn; 1.7\u0026deg;), respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMedial versus Lateral Pivoting Throughout Squatting\u003c/p\u003e\u003cp\u003eThe density plot for CPAK type III knees exhibited a bimodal pattern, showing a medial pivoting motion up to mid-flexion, which then shifted to a lateral pivoting motion from mid-flexion to deep flexion (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Each of the 17 CPAK type III knees exhibited a lateral center of rotation (lateral pivot) during squatting, whereas for 8 of these 17 lateral pivoting was the predominant pattern, extending over more than half of the flexion range (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Furthermore, the likelihood of observing lateral pivot motion, across all subjects and knee flexion angles, was 48.1%.\u003c/p\u003e\u003cp\u003eAmong the specimens, the proportion of lateral pivoting motion across the entire range of knee flexion varied from 9.23\u0026ndash;100%, with a mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D. of 48\u0026thinsp;\u0026plusmn;\u0026thinsp;27.62% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Additionally, throughout the full range of knee flexion, the medial femoral condyle showed a total translation ranging between 0.05 and 0.41 across specimens (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D. = 0.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1). Similarly, the lateral femoral condyle demonstrated a translation ranging from 0.06 to 0.50 (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D. = 0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1), (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003eThe GLM model demonstrated that the effects of aHKA (p\u0026thinsp;=\u0026thinsp;0.922) and JLO (p\u0026thinsp;=\u0026thinsp;0.833) on lateral pivot motion were not statistically significant. Nevertheless, the knee flexion angle exhibited a significant impact (p\u0026thinsp;=\u0026thinsp;0.024), showing that increased flexion was associated with a higher occurrence of lateral pivoting. Overall, lateral pivoting predominantly occurred when the knee flexion angle was \u0026ge;\u0026thinsp;58.5\u0026deg; (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eA).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this was the first study to assess the relationship between pivoting motion and the CPAK phenotypes, more specifically type III. The main finding of this study was that all CPAK type III specimens exhibited a lateral center of rotation (lateral pivot) during loaded squatting and primarily occurring from mid to deep flexion. These results thus align with our hypothesis that the weight-bearing squatting motion is associated with lateral pivot motion in the CPAK type III knees.\u003c/p\u003e\u003cp\u003eAt first sight, our finding conflicts with prior research that identified a medial pivoting motion as the main kinematic pattern throughout flexion of the native knee joint\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Although medial pivot motion has indeed been observed in non-weight-bearing passive flexion of the knee\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e as well as weight-bearing squat exercises\u003csup\u003e\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e, it is critical to mention that none of these studies explicitly references their findings to the lower extremity alignment. One possible explanation for the consistent reports of medial pivot could be that these studies were biased by the higher incidence of constitutional varus knees, leading to the lateral pivot seen in valgus knees, such as in CPAK III, being either underrepresented or not observed\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe term \u0026ldquo;lateral pivot motion\u0026rdquo; itself is not new and has been reported in the past. As mentioned above, more recent investigations of native knee kinematics have revealed that earlier stages of knee flexion associated with activities like walking, running, or pivoting are characterized by a lateral pivot pattern\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. On the other hand, to the best of our knowledge, there are no systematic reports of such lateral pivot motion in deep flexion. Engel et al. reported that 8 out of 9 cadaveric knees showed a medial center of rotation during squatting, whereas 1 knee showed a lateral center of rotation\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Also, Komistek et al. described a fluoroscopic \u003cem\u003ein vivo\u003c/em\u003e study in which the majority of 5 native knees showed medial pivoting, but one knee showed a lateral pivot motion in gait and deeper flexion\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. Whether these lateral pivoting knees demonstrated valgus alignment unfortunately remains unknown for both studies, but is highly probable given the distribution of the Caucasian population in terms of lower extremity alignment\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Nevertheless, these studies do indicate that pivoting of the knee joint might be more complex than previously thought. Importantly, the bimodal pattern we observed in our study, characterized by a shift from medial to lateral pivoting for increasing flexion (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003eA) adds to this complexity. Hence, the systematic integration of lower extremity alignment and its phenotypes in knee kinematic studies, as done in this study, has the potential to unravel this complexity. Interestingly, a very recent investigation in the correlation between knee alignment phenotypes and cartilage degeneration also suggests that a more detailed analysis of limb axis deformities should complement the assessment of cartilage and planning of an intervention\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Although this study was not based on CPAK, this study did highlight that, in addition to the general trend of valgus alignment being linked to lateral wear, tibial valgus is associated with medial cartilage degeneration\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Although the mechanistic interaction between cartilage wear and pivoting motion requires further research, the combined occurrence of medial and lateral wear thus seems to align with the bimodal pivoting pattern throughout flexion we observed in our study. Furthermore, this study indicated that the combination of a valgus femur with varus tibia phenotypes, as present in CPAK\u0026rsquo;s type III phenotypes, exhibited a strong, atypical correlation with the anterior lateral tibial subregion which importantly aligns with our finding of lateral pivoting as the main kinematic pattern and the underlying assumption of a primarily lateral transfer of tibiofemoral contact forces.\u003c/p\u003e\u003cp\u003eAnother potential confounder to consider when discussing the native knee\u0026rsquo;s pivoting behavior is the inclusion of weight- or non-weight-bearing kinematics as it is well-known that the weight-bearing kinematics differ from the non-weight-bearing\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Interestingly, a complementary kinematic analysis of this study\u0026rsquo;s cohort of valgus-aligned CPAK Type III specimens during passive flexion-extension did not reveal any lateral pivoting motion (See Supplementary Information). One potential reason for the differing pivot motion observed during squatting and passive flexion-extension in a valgus knee might be the way tibiofemoral contact forces are distributed between the knee\u0026rsquo;s medial and lateral compartments while bearing weight. Lerner et al. have observed that aligning the knee joint to the valgus position results in increased contact pressure at the lateral joint surface and shifts in the contact point locations\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Furthermore, this redistribution of contact forces, and hence also the lateral pivoting we observed, aligns with valgus alignment being a commonly accepted cause of lateral compartment wear\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Finally, the absence of any co-contraction in passive flexion further contributes to this differing pivot motion\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur finding that native CPAK type III specimens exhibit a lateral center of rotation (lateral pivot) during squatting also has important clinical relevance. Indeed, as patient satisfaction is assumed to be correlated with TKA\u0026rsquo;s ability to restore kinematics more closely to the native knee\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, these results provide a first indication for the clinical potential of implants that allow for a lateral pivot motion during weight-bearing motor tasks that involve deep flexion such as squatting, sit-stand-sit, or stair ascending and descending tasks. In this context, clinical results of a dual pivot TKA design have been recently reported\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. However, the lateral pivot motion of this implant design is induced only in earlier stages of the flexion and not during deep flexion. Furthermore, the relationship between the clinical outcome of this implant and alignment phenotypes was not analysed. Hence, the proportion within their cohort of CPAK Type III subjects potentially showing native lateral pivoting remains unknown. Iwakiri et al. (40) analysed the clinical outcome of medial pivot TKA in the valgus knee. Although clinical outcomes were reported to be similar as in the varus knee, the number of valgus cases was small and underpowered. Therefore, the current literature remains inconclusive as to which implant design best fits the valgus knee. Furthermore, valgus knees still present with additional surgical challenges that might affect post-TKA kinematics\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, including but not limited to the definition of alignment targets in constitutional valgus phenotypes such as CPAK III. Lastly, also the substantial specimen-to-specimen variation in the proportion of lateral pivoting throughout the flexion range complicates the design optimization for valgus knees. Furthermore, our results indicate that this variation cannot be attributed to alignment features of the CPAK classification as JLO and aHKA had no significant impact on the occurrence of lateral pivoting. Nevertheless, we believe the current study offers important data and insights to be considered for subsequent research on the role of native valgus knee kinematics in the optimization of TKA outcomes.\u003c/p\u003e\u003cp\u003eSeveral methodological aspects of this study require further discussion. First, the CPAK classification was originally designed to be conducted by means of two-dimensional (2D) full-length lower limb standing radiograph\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, because of its wide clinical availability. Nevertheless, accurate evaluation of the inherently three-dimensional (3D) lower limb alignment with 2D medical imaging is at risk of being confounded by lower limb rotation and flexion contractures\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Therefore, recent studies suggested the use of three-dimensional (3D) CT\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and reported that 3D CT measurements of MPTA and LDFA were more reproducible and had a good correlation with two-dimensional measurements\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. However, one of the recurrent challenges in 3D CT measurement is that the 3D definition of the tibial joint line varies throughout the literature, and consensus yet has to be reached. F\u0026uuml;rmetz et al. defined the joint line as the line connecting the medial and lateral most cranial points on the tibial plateau\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. Ho et al.\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e reported the best matching surfaces for the medial and lateral sides of the proximal tibia, and Micicoi et al.\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e similarly specified 35 points and used a plane that coincided with the articular surface. Le\u0026oacute;n-Mu\u0026ntilde;oz et al.\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e and Gieroba et al.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e used the deepest points of the tibial plateau, as in the present study. Given the complex morphology of the tibiofemoral joint, the deepest point was considered a more accurate and reproducible measurement method\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. Secondly, our 3D CT-based analysis was non-weight-bearing in contrast with the original CPAK classification methodology. However, prior research from our group identified that deformity increases with loading\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. Therefore, our selection of CPAK type III phenotypes was likely overly conservative, which further adds to the strength of our study. Nevertheless, further research on CPAK classification with 3D, weight-bearing measurements is warranted.\u003c/p\u003e\u003cp\u003eSecondly, our kinematic analysis was based on the geometric center axis of the distal femur (GCA). More specifically, spheres that fit the flexion facets of the medial and lateral posterior condyles (FMCC and FLCC) were used to define the GCA\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. This GCA was then projected onto the tibial plane to evaluate anteroposterior condyle translations and, hence, identify the pivoting motion of the knee\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Nevertheless, other studies relied on the trans-epicondylar axis (TEA). Although both have been extensively used in past studies\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e, it has been reported that the choice between both can affect the identification of kinematic patterns underlying a given knee movement\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. Rao et al. advocated that, without considering the intricate patterns of knee motion along the flexion path, the TEA may oversimplify the fundamental link between the anatomy and kinematics of the knee\u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e. Mochizuki et al. also stated that the TEA was not a good surrogate for the functional flexion axis\u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. Based on these studies, we preferred GCA over TEA. Other possible kinematic analysis approaches include contact estimates, lowest point kinematics, and functional axes\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e. However, there is still controversy as to which method is the most appropriate, warranting further research.\u003c/p\u003e\u003cp\u003eThirdly, specimens considered to have severe OA were excluded from this study. The primary motivation behind this was that this study targeted the identification of native kinematics. According to Hamai et al., patients with medial OA have different weight-bearing kinematics than native knees\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. Furthermore, it is well known that anterior cruciate ligament (ACL) dysfunction has a coherent relationship with OA\u003csup\u003e\u003cspan additionalcitationids=\"CR59\" citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e. Murayama et al. reported that the motion pattern of ACL dysfunctional knees was different from that of the contralateral, healthy knees\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Dennis et al. also found that the center of rotation of normal and ACL dysfunctional subjects differ significantly\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. Based on these studies, we aimed to prevent our conclusions from being affected by (1) changes in joint surface shape due to severe OA and/or (2) ACL dysfunction due to severe OA.\u003c/p\u003e\u003cp\u003eFourthly, this study made use of a physiological \u003cem\u003eex vivo\u003c/em\u003e knee simulator to mimic the native function of the knee joint. Alternatively, intraoperative navigation systems have been used to assess knee kinematics during surgery\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. However, this method only allows the assessment of passive knee function in a non-weight-bearing state. Alternatively, \u003cem\u003ein vivo\u003c/em\u003e analysis using fluoroscopy is often performed \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e, but this has the disadvantage of exposing the subject to high levels of radiation, in addition to practical and financial constraints. Moreover, it is also known that there are limitations to the accuracy of reproduction of natural activity\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. In other words, natural, unrestricted motion, such as squatting, is difficult to analyse in larger cohorts given the specific constraints of fluoroscopes. On the other hand, the use of a physiological \u003cem\u003eex vivo\u003c/em\u003e knee simulator is an alternative complementary assessment method that mimics the weight-bearing situations while applying physiological muscle loads, which is not limited to ethical, time, and practical constraints compared to \u003cem\u003ein vivo\u003c/em\u003e testing\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e\u003c/sup\u003e. The simulator used in this study, and hence the uniquely large cohort of specimens analysed with it, has been proven reliable and useful in previous studies\u003csup\u003e\u003cspan additionalcitationids=\"CR63\" citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNevertheless, this study has several remaining limitations. First, despite prior studies documenting the representativeness of such cadaveric simulations for \u003cem\u003ein vivo\u003c/em\u003e knee function\u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e, care should still be taken when extrapolating these findings to \u003cem\u003ein vivo\u003c/em\u003e knee joint kinematics during a wider range of daily life motor tasks. Secondly, this study only investigated pivoting motion within knee flexion ranging from 35 to 100\u0026deg;. Therefore, the pivoting behaviour in extension and early flexion could not be investigated. Thirdly, our study used a simplified definition of medial and lateral pivoting compared to more detailed or restricted approaches reported in the literature. Previous studies have used methods such as the mean of overall pivoting to identify the center of rotation\u003csup\u003e\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e or categorized motion into distinct types\u0026mdash;no pivot, medial pivot, lateral pivot, and central pivot\u0026mdash;over the knee flexion angle\u003csup\u003e\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e. In contrast, we assessed pivoting throughout the entire range of motion without focusing on a single mean or restricting to specific definitions. Fourthly, we did not analyse the influence of patellar tracking, which might be a contributing factor for the lateral pivoting. The patella fits into the trochlear groove during flexion, affecting the pressure on the tibiofemoral joint\u003csup\u003e\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e. However, it remains unclear how patella alignment affects pivot motion\u003csup\u003e\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e. Further studies are required for understanding the relationship between the patellar tracking and pivot motion. Finally, our findings are based on a limited sample of only 17 CPAK type III knees and may not be representative of the entire population with valgus alignment, especially the cases with a higher aHKA or lower JLO.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study analysed the relationship between pivot motion during squatting and lower extremity valgus alignment (CPAK classification) and showed that a lateral pivot motion pattern occurred during squatting in approximately half of CPAK type III specimens from mid to deep flexion when tested in a loaded knee simulator. The current study offers essential data and insights to be considered for subsequent research on the role of native valgus knee kinematics in optimizing TKA outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to ethical restrictions, as the data were obtained from previously tested human donor specimens. Access to the data is available from the corresponding author upon reasonable request and subject to approval by the senior author and their affiliated university. The source data from which the results were generated and analysed are included in the Supplementary Information document.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eG.P. drafted the first manuscript of this article, coordinated the manuscript with all co-authors, supervised all aspects, interpreted the results and revised manuscript sections. O.T. collected measurements, developed the code for data processing, post-processed all data, and analysed the results, drafted the first manuscript of this article, coordinated the manuscript with all co-authors recruited participants, revised manuscript sections. J.I. and G.P. post-processed some of the data, analysed the results, and drafted the first manuscript of this article. J.B. developed the research agenda behind this work, revised manuscript sections and supervised all aspects. L.S. collected measurements, developed the research agenda behind this work, interpreted the results, revised manuscript sections and supervised all aspects. All authors contributed to the study design, interpreted the results, wrote and revised manuscript sections, read and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUse of human tissue samples\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study involved only previously collected data from cadaveric human donor specimens, which were originally tested as part of earlier ethically approved studies. No new experiments involving human participants or the collection of human tissue were conducted for this study. All methods utilized in the original studies received approval from the Local KU Leuven Ethics Committee in accordance with relevant guidelines and regulations. Due to the retrospective nature of the study, the Local KU Leuven Ethics Committee waived the need of obtaining informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare declare no potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eInui, H., Yamagami, R., Kono, K. \u0026amp; Kawaguchi, K. What are the causes of failure after total knee arthroplasty? \u003cem\u003eJ. Joint Surg. Res.\u003c/em\u003e \u003cstrong\u003e1\u003c/strong\u003e, 32\u0026ndash;40 (2023).\u003c/li\u003e\n \u003cli\u003eMurakami, K. et al\u003cem\u003e.\u003c/em\u003e Kinematic analysis of stair climbing in rotating platform cruciate-retaining and posterior-stabilized mobile-bearing total knee arthroplasties. \u003cem\u003eArch. Orthop. 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Arthroplasty\u003c/em\u003e \u003cstrong\u003e29\u003c/strong\u003e, 2305\u0026ndash;2308 (2014).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"lateral pivot, coronal plane alignment of the knee (CPAK), valgus, squatting, kinematics","lastPublishedDoi":"10.21203/rs.3.rs-6385860/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6385860/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMedial pivoting motion has been identified as the primary kinematic pattern throughout flexion of the native knee joint. The recently introduced coronal plane alignment of the knee (CPAK) classification categorizes knees into nine alignment-based phenotypes, yet the relationship between these phenotypes and their respective kinematic behavior remains poorly documented, particularly in less common valgus phenotypes. Therefore, this study aimed to perform a detailed analysis of the pivoting motion of the CPAK type III knees during \u003cem\u003eex vivo\u003c/em\u003e simulated squatting. Considering the more lateral weight-bearing axis in the valgus phenotype, we hypothesized that weight-bearing motion is associated with lateral pivot motion.\u003c/p\u003e\u003cp\u003eWe retrospectively analysed a previously collected dataset of sixty-nine native fresh-frozen cadaveric knees subjected to squatting motion (35\u0026deg;-100\u0026deg;) on a physiological knee joint simulator. Seventeen CPAK Type III knees were identified based on full-leg computed tomography scans. Next, we discerned between medial and lateral pivoting throughout the range of motion based on the location of the instantaneous center of rotation (ICOR) to the center of the tibial plateau. Furthermore, we screened for possible associations between CPAK\u0026rsquo;s coronal lower limb alignment features and lateral pivoting. All 17 CPAK type III knees exhibited a lateral center of rotation during squatting, with 8 demonstrating lateral pivoting as the predominant pattern over more than half of the flexion range. This study showed that a lateral pivot motion pattern occurred during squatting in approximately half of the CPAK type III specimens, from mid to deep flexion (58.5\u0026deg;-100\u0026deg;) when tested in a loaded knee simulator. The current study offers essential data and insights to be considered for subsequent research on the role of native valgus knee kinematics in optimizing TKA outcomes.\u003c/p\u003e","manuscriptTitle":"Coronal Plane Alignment Of The Knee (CPAK) Type III Valgus Knee Exhibits Lateral Pivot Motion During Squatting","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-31 16:23:56","doi":"10.21203/rs.3.rs-6385860/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"038c8129-33d8-4029-860c-f17f22d38162","owner":[],"postedDate":"July 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52334708,"name":"Health sciences/Anatomy"},{"id":52334709,"name":"Health sciences/Medical research"},{"id":52334710,"name":"Physical sciences/Physics"}],"tags":[],"updatedAt":"2025-08-20T07:08:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-31 16:23:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6385860","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6385860","identity":"rs-6385860","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}