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Aims. Classifying trochlear dysplasia (TD) is useful to determine the treatment options for patients suffering from patellofemoral instability (PFI). There is no consensus on which classification system is more reliable and reproducible for the purpose of guiding clinicians’ management of PFI. There are also concerns about the validity of the Dejour Classification (DJC), which is the most widely used classification for TD, having only a fair reliability score. The Oswestry-Bristol Classification (OBC) is a recently proposed system of classification of TD, and the authors report a fair-to-good interobserver agreement and good-to-excellent intraobserver agreement in the assessment of TD. The aim of this study was to compare the reliability and reproducibility of these two classifications. Methods. In all, six assessors (four consultants and two registrars) independently evaluated 100 axial MRIs of the patellofemoral joint (PFJ) for TD and classified them according to OBC and DJC. These assessments were again repeated by all raters after four weeks. The inter- and intraobserver reliability scores were calculated using Cohen’s kappa and Cronbach’s α. Results. Both classifications showed good to excellent interobserver reliability with high α scores. The OBC classification showed a substantial intraobserver agreement (mean kappa 0.628; p < 0.005) whereas the DJC showed a moderate agreement (mean kappa 0.572; p < 0.005). There was no significant difference in the kappa values when comparing the assessments by consultants with those by registrars, in either classification system. Conclusion. This large study from a non-founding institute shows both classification systems to be reliable for classifying TD based on axial MRIs of the PFJ, with the simple-to-use OBC having a higher intraobserver reliability score than that of the DJC. Cite this article: Bone Jt Open 2023;4(7):532–538


Bone & Joint Research
Vol. 12, Issue 5 | Pages 313 - 320
8 May 2023
Saiki Y Kabata T Ojima T Kajino Y Kubo N Tsuchiya H

Aims. We aimed to assess the reliability and validity of OpenPose, a posture estimation algorithm, for measurement of knee range of motion after total knee arthroplasty (TKA), in comparison to radiography and goniometry. Methods. In this prospective observational study, we analyzed 35 primary TKAs (24 patients) for knee osteoarthritis. We measured the knee angles in flexion and extension using OpenPose, radiography, and goniometry. We assessed the test-retest reliability of each method using intraclass correlation coefficient (1,1). We evaluated the ability to estimate other measurement values from the OpenPose value using linear regression analysis. We used intraclass correlation coefficients (2,1) and Bland–Altman analyses to evaluate the agreement and error between radiography and the other measurements. Results. OpenPose had excellent test-retest reliability (intraclass correlation coefficient (1,1) = 1.000). The R. 2. of all regression models indicated large correlations (0.747 to 0.927). In the flexion position, the intraclass correlation coefficients (2,1) of OpenPose indicated excellent agreement (0.953) with radiography. In the extension position, the intraclass correlation coefficients (2,1) indicated good agreement of OpenPose and radiography (0.815) and moderate agreement of goniometry with radiography (0.593). OpenPose had no systematic error in the flexion position, and a 2.3° fixed error in the extension position, compared to radiography. Conclusion. OpenPose is a reliable and valid tool for measuring flexion and extension positions after TKA. It has better accuracy than goniometry, especially in the extension position. Accurate measurement values can be obtained with low error, high reproducibility, and no contact, independent of the examiner’s skills. Cite this article: Bone Joint Res 2023;12(5):313–320


Bone & Joint Open
Vol. 1, Issue 7 | Pages 355 - 358
7 Jul 2020
Konrads C Gonser C Ahmad SS

Aims. The Oswestry-Bristol Classification (OBC) was recently described as an MRI-based classification tool for the femoral trochlear. The authors demonstrated better inter- and intraobserver agreement compared to the Dejour classification. As the OBC could potentially provide a very useful MRI-based grading system for trochlear dysplasia, it was the aim to determine the inter- and intraobserver reliability of the classification system from the perspective of the non-founder. Methods. Two orthopaedic surgeons independently assessed 50 MRI scans for trochlear dysplasia and classified each according to the OBC. Both observers repeated the assessments after six weeks. The inter- and intraobserver agreement was determined using Cohen’s kappa statistic and S-statistic nominal and linear weights. Results. The OBC with grading into four different trochlear forms showed excellent inter- and intraobserver agreement with a mean kappa of 0.78. Conclusion. The OBC is a simple MRI-based classification system with high inter- and intraobserver reliability. It could present a useful tool for grading the severity of trochlear dysplasia in daily practice. Cite this article: Bone Joint Open 2020;1-7:355–358


Bone & Joint Research
Vol. 2, Issue 1 | Pages 1 - 8
1 Jan 2013
Costa AJ Lustig S Scholes CJ Balestro J Fatima M Parker DA

Objectives. There remains a lack of data on the reliability of methods to estimate tibial coverage achieved during total knee replacement. In order to address this gap, the intra- and interobserver reliability of a three-dimensional (3D) digital templating method was assessed with one symmetric and one asymmetric prosthesis design. Methods. A total of 120 template procedures were performed according to specific rotational and over-hang criteria by three observers at time zero and again two weeks later. Total and sub-region coverage were calculated and the reliability of the templating and measurement method was evaluated. Results. Excellent intra- and interobserver reliability was observed for total coverage, when minimal component overhang (intraclass correlation coefficient (ICC) = 0.87) or no component overhang (ICC = 0.92) was permitted, regardless of rotational restrictions. Conclusions. Measurement of tibial coverage can be reliable using the templating method described even if the rotational axis selected still has a minor influence


Bone & Joint Research
Vol. 11, Issue 9 | Pages 619 - 628
7 Sep 2022
Yapp LZ Scott CEH Howie CR MacDonald DJ Simpson AHRW Clement ND

Aims. The aim of this study was to report the meaningful values of the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) and EuroQol visual analogue scale (EQ-VAS) in patients undergoing primary knee arthroplasty (KA). Methods. This is a retrospective study of patients undergoing primary KA for osteoarthritis in a university teaching hospital (Royal Infirmary of Edinburgh) (1 January 2013 to 31 December 2019). Pre- and postoperative (one-year) data were prospectively collected for 3,181 patients (median age 69.9 years (interquartile range (IQR) 64.2 to 76.1); females, n = 1,745 (54.9%); median BMI 30.1 kg/m. 2. (IQR 26.6 to 34.2)). The reliability of the EQ-5D-3L was measured using Cronbach’s alpha. Responsiveness was determined by calculating the anchor-based minimal clinically important difference (MCID), the minimal important change (MIC) (cohort and individual), the patient-acceptable symptom state (PASS) predictive of satisfaction, and the minimal detectable change at 90% confidence intervals (MDC-90). Results. The EQ-5D-3L demonstrated good internal consistency with an overall Cronbach alpha of 0.75 (preoperative) and 0.88 (postoperative), respectively. The MCID for the Index score was 0.085 (95% confidence interval (CI) 0.042 to 0.127) and EQ-VAS was 6.41 (95% CI 3.497 to 9.323). The MIC. COHORT. was 0.289 for the EQ-5D and 5.27 for the EQ-VAS. However, the MIC. INDIVIDUAL. for both the EQ-5D-3L Index (0.105) and EQ-VAS (-1) demonstrated poor-to-acceptable reliability. The MDC-90 was 0.023 for the EQ-5D-3L Index and 1.0 for the EQ-VAS. The PASS for the postoperative EQ-5D-3L Index and EQ-VAS scores predictive of patient satisfaction were 0.708 and 77.0, respectively. Conclusion. The meaningful values of the EQ-5D-3L Index and EQ-VAS scores can be used to measure clinically relevant changes in health-related quality of life in patients undergoing primary KA. Cite this article: Bone Joint Res 2022;11(9):619–628


Bone & Joint Open
Vol. 2, Issue 8 | Pages 638 - 645
1 Aug 2021
Garner AJ Edwards TC Liddle AD Jones GG Cobb JP

Aims. Joint registries classify all further arthroplasty procedures to a knee with an existing partial arthroplasty as revision surgery, regardless of the actual procedure performed. Relatively minor procedures, including bearing exchanges, are classified in the same way as major operations requiring augments and stems. A new classification system is proposed to acknowledge and describe the detail of these procedures, which has implications for risk, recovery, and health economics. Methods. Classification categories were proposed by a surgical consensus group, then ranked by patients, according to perceived invasiveness and implications for recovery. In round one, 26 revision cases were classified by the consensus group. Results were tested for inter-rater reliability. In round two, four additional cases were added for clarity. Round three repeated the survey one month later, subject to inter- and intrarater reliability testing. In round four, five additional expert partial knee arthroplasty surgeons were asked to classify the 30 cases according to the proposed revision partial knee classification (RPKC) system. Results. Four classes were proposed: PR1, where no bone-implant interfaces are affected; PR2, where surgery does not include conversion to total knee arthroplasty, for example, a second partial arthroplasty to a native compartment; PR3, when a standard primary total knee prosthesis is used; and PR4 when revision components are necessary. Round one resulted in 92% inter-rater agreement (Kendall’s W 0.97; p < 0.005), rising to 93% in round two (Kendall’s W 0.98; p < 0.001). Round three demonstrated 97% agreement (Kendall’s W 0.98; p < 0.001), with high intra-rater reliability (interclass correlation coefficient (ICC) 0.99; 95% confidence interval 0.98 to 0.99). Round four resulted in 80% agreement (Kendall’s W 0.92; p < 0.001). Conclusion. The RPKC system accounts for all procedures which may be appropriate following partial knee arthroplasty. It has been shown to be reliable, repeatable and pragmatic. The implications for patient care and health economics are discussed. Cite this article: Bone Jt Open 2021;2(8):638–645


Bone & Joint Open
Vol. 4, Issue 4 | Pages 262 - 272
11 Apr 2023
Batailler C Naaim A Daxhelet J Lustig S Ollivier M Parratte S

Aims. The impact of a diaphyseal femoral deformity on knee alignment varies according to its severity and localization. The aims of this study were to determine a method of assessing the impact of diaphyseal femoral deformities on knee alignment for the varus knee, and to evaluate the reliability and the reproducibility of this method in a large cohort of osteoarthritic patients. Methods. All patients who underwent a knee arthroplasty from 2019 to 2021 were included. Exclusion criteria were genu valgus, flexion contracture (> 5°), previous femoral osteotomy or fracture, total hip arthroplasty, and femoral rotational disorder. A total of 205 patients met the inclusion criteria. The mean age was 62.2 years (SD 8.4). The mean BMI was 33.1 kg/m. 2. (SD 5.5). The radiological measurements were performed twice by two independent reviewers, and included hip knee ankle (HKA) angle, mechanical medial distal femoral angle (mMDFA), anatomical medial distal femoral angle (aMDFA), femoral neck shaft angle (NSA), femoral bowing angle (FBow), the distance between the knee centre and the top of the FBow (DK), and the angle representing the FBow impact on the knee (C’KS angle). Results. The FBow impact on the mMDFA can be measured by the C’KS angle. The C’KS angle took the localization (length DK) and the importance (FBow angle) of the FBow into consideration. The mean FBow angle was 4.4° (SD 2.4; 0 to 12.5). The mean C’KS angle was 1.8° (SD 1.1; 0 to 5.8). Overall, 84 knees (41%) had a severe FBow (> 5°). The radiological measurements showed very good to excellent intraobserver and interobserver agreements. The C’KS increased significantly when the length DK decreased and the FBow angle increased (p < 0.001). Conclusion. The impact of the diaphyseal femoral deformity on the mechanical femoral axis is measured by the C’KS angle, a reliable and reproducible measurement. Cite this article: Bone Jt Open 2023;4(4):262–272


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1075 - 1081
17 Dec 2021
Suthar A Yukata K Azuma Y Suetomi Y Yamazaki K Seki K Sakai T Fujii H

Aims. This study aimed to investigate the relationship between changes in patellar height and clinical outcomes at a mean follow-up of 7.7 years (5 to 10) after fixed-bearing posterior-stabilized total knee arthroplasty (PS-TKA). Methods. We retrospectively evaluated knee radiographs of 165 knees, which underwent fixed-bearing PS-TKA with patella resurfacing. The incidence of patella baja and changes in patellar height over a minimum of five years of follow-up were determined using Insall-Salvati ratio (ISR) measurement. We examined whether patella baja (ISR < 0.8) at final follow-up affected clinical outcomes, knee joint range of motion (ROM), and Knee Society Score (KSS). We also assessed inter- and intrarater reliability of ISR measurements and focused on the relationship between patellar height reduction beyond measurement error and clinical outcomes. Results. The ISR gradually decreased over five years after TKA, and finally 33 patients (20.0%) had patella baja. Patella baja at the final follow-up was not related to passive knee ROM or KSS. Interestingly, when we divided into two groups - patella baja and patella normal-alta (ISR ≥ 0.8) - the patella baja group already had a lower patellar height before surgery, compared with the patella normal-alta group. The ISR measurement error in this study was 0.17. Both passive knee flexion and KSS were significantly decreased in the group with a decrease in ISR of ≥ 0.17 at final follow-up. Conclusion. Patellar height gradually decreased over five years of follow-up after TKA. The reduction in patellar height beyond measurement error following TKA was associated with lower clinical outcomes. Cite this article: Bone Jt Open 2021;2(12):1075–1081


Bone & Joint Research
Vol. 7, Issue 7 | Pages 468 - 475
1 Jul 2018
He Q Sun H Shu L Zhu Y Xie X Zhan Y Luo C

Objectives. Researchers continue to seek easier ways to evaluate the quality of bone and screen for osteoporosis and osteopenia. Until recently, radiographic images of various parts of the body, except the distal femur, have been reappraised in the light of dual-energy X-ray absorptiometry (DXA) findings. The incidence of osteoporotic fractures around the knee joint in the elderly continues to increase. The aim of this study was to propose two new radiographic parameters of the distal femur for the assessment of bone quality. Methods. Anteroposterior radiographs of the knee and bone mineral density (BMD) and T-scores from DXA scans of 361 healthy patients were prospectively analyzed. The mean cortical bone thickness (CBTavg) and the distal femoral cortex index (DFCI) were the two parameters that were proposed and measured. Intra- and interobserver reliabilities were assessed. Correlations between the BMD and T-score and these parameters were investigated and their value in the diagnosis of osteoporosis and osteopenia was evaluated. Results. The DFCI, as a ratio, had higher reliability than the CBTavg. Both showed significant correlation with BMD and T-score. When compared with DFCI, CBTavg showed better correlation and was better for predicting osteoporosis and osteopenia. Conclusion. The CBTavg and DFCI are simple and reliable screening tools for the prediction of osteoporosis and osteopenia. The CBTavg is more accurate but the DFCI is easier to use in clinical practice. Cite this article: Q-F. He, H. Sun, L-Y. Shu, Y. Zhu, X-T. Xie, Y. Zhan, C-F. Luo. Radiographic predictors for bone mineral loss: Cortical thickness and index of the distal femur. Bone Joint Res 2018;7:468–475. DOI: 10.1302/2046-3758.77.BJR-2017-0332.R1


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 885 - 893
14 Nov 2022
Goshima K Sawaguchi T Horii T Shigemoto K Iwai S

Aims

To evaluate whether low-intensity pulsed ultrasound (LIPUS) accelerates bone healing at osteotomy sites and promotes functional recovery after open-wedge high tibial osteotomy (OWHTO).

Methods

Overall, 90 patients who underwent OWHTO without bone grafting were enrolled in this nonrandomized retrospective study, and 45 patients treated with LIPUS were compared with 45 patients without LIPUS treatment in terms of bone healing and functional recovery postoperatively. Clinical evaluations, including the pain visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score, were performed preoperatively as well as six weeks and three, six, and 12 months postoperatively. The progression rate of gap filling was evaluated using anteroposterior radiographs at six weeks and three, six, and 12 months postoperatively.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 879 - 885
14 Oct 2024
Moore J van de Graaf VA Wood JA Humburg P Colyn W Bellemans J Chen DB MacDessi SJ

Aims

This study examined windswept deformity (WSD) of the knee, comparing prevalence and contributing factors in healthy and osteoarthritic (OA) cohorts.

Methods

A case-control radiological study was undertaken comparing 500 healthy knees (250 adults) with a consecutive sample of 710 OA knees (355 adults) undergoing bilateral total knee arthroplasty. The mechanical hip-knee-ankle angle (mHKA), medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were determined for each knee, and the arithmetic hip-knee-ankle angle (aHKA), joint line obliquity, and Coronal Plane Alignment of the Knee (CPAK) types were calculated. WSD was defined as a varus mHKA of < -2° in one limb and a valgus mHKA of > 2° in the contralateral limb. The primary outcome was the proportional difference in WSD prevalence between healthy and OA groups. Secondary outcomes were the proportional difference in WSD prevalence between constitutional varus and valgus CPAK types, and to explore associations between predefined variables and WSD within the OA group.


Bone & Joint Open
Vol. 4, Issue 6 | Pages 399 - 407
1 Jun 2023
Yeramosu T Ahmad W Satpathy J Farrar JM Golladay GJ Patel NK

Aims

To identify variables independently associated with same-day discharge (SDD) of patients following revision total knee arthroplasty (rTKA) and to develop machine learning algorithms to predict suitable candidates for outpatient rTKA.

Methods

Data were obtained from the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) database from the years 2018 to 2020. Patients with elective, unilateral rTKA procedures and a total hospital length of stay between zero and four days were included. Demographic, preoperative, and intraoperative variables were analyzed. A multivariable logistic regression (MLR) model and various machine learning techniques were compared using area under the curve (AUC), calibration, and decision curve analysis. Important and significant variables were identified from the models.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 624 - 635
4 Oct 2023
Harrison CJ Plessen CY Liegl G Rodrigues JN Sabah SA Beard DJ Fischer F

Aims

To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.

Methods

Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


Bone & Joint Open
Vol. 3, Issue 10 | Pages 767 - 776
5 Oct 2022
Jang SJ Kunze KN Brilliant ZR Henson M Mayman DJ Jerabek SA Vigdorchik JM Sculco PK

Aims

Accurate identification of the ankle joint centre is critical for estimating tibial coronal alignment in total knee arthroplasty (TKA). The purpose of the current study was to leverage artificial intelligence (AI) to determine the accuracy and effect of using different radiological anatomical landmarks to quantify mechanical alignment in relation to a traditionally defined radiological ankle centre.

Methods

Patients with full-limb radiographs from the Osteoarthritis Initiative were included. A sub-cohort of 250 radiographs were annotated for landmarks relevant to knee alignment and used to train a deep learning (U-Net) workflow for angle calculation on the entire database. The radiological ankle centre was defined as the midpoint of the superior talus edge/tibial plafond. Knee alignment (hip-knee-ankle angle) was compared against 1) midpoint of the most prominent malleoli points, 2) midpoint of the soft-tissue overlying malleoli, and 3) midpoint of the soft-tissue sulcus above the malleoli.


Aims

The aim of this study was to compare the preinjury functional scores with the postinjury preoperative score and postoperative outcome scores following anterior cruciate ligament (ACL) reconstruction surgery (ACLR).

Methods

We performed a prospective study on patients who underwent primary ACLR by a single surgeon at a single centre between October 2010 and January 2018. Preoperative preinjury scores were collected at time of first assessment after the index injury. Preoperative (pre- and post-injury), one-year, and two-year postoperative functional outcomes were assessed by using the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score, and Tegner Activity Scale.


Bone & Joint Open
Vol. 4, Issue 9 | Pages 682 - 688
6 Sep 2023
Hampton M Balachandar V Charalambous CP Sutton PM

Aims

Aseptic loosening is the most common cause of failure following cemented total knee arthroplasty (TKA), and has been linked to poor cementation technique. We aimed to develop a consensus on the optimal technique for component cementation in TKA.

Methods

A UK-based, three-round, online modified Delphi Expert Consensus Study was completed focusing on cementation technique in TKA. Experts were identified as having a minimum of five years’ consultant experience in the NHS and fulfilling any one of the following criteria: a ‘high volume’ knee arthroplasty practice (> 150 TKAs per annum) as identified from the National joint Registry of England, Wales, Northern Ireland and the Isle of Man; a senior author of at least five peer reviewed articles related to TKA in the previous five years; a surgeon who is named trainer for a post-certificate of comletion of training fellowship in TKA.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 681 - 687
19 Aug 2024
van de Graaf VA Shen TS Wood JA Chen DB MacDessi SJ

Aims

Sagittal plane imbalance (SPI), or asymmetry between extension and flexion gaps, is an important issue in total knee arthroplasty (TKA). The purpose of this study was to compare SPI between kinematic alignment (KA), mechanical alignment (MA), and functional alignment (FA) strategies.

Methods

In 137 robotic-assisted TKAs, extension and flexion stressed gap laxities and bone resections were measured. The primary outcome was the proportion and magnitude of medial and lateral SPI (gap differential > 2.0 mm) for KA, MA, and FA. Secondary outcomes were the proportion of knees with severe (> 4.0 mm) SPI, and resection thicknesses for each technique, with KA as reference.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 109 - 116
8 Feb 2024
Corban LE van de Graaf VA Chen DB Wood JA Diwan AD MacDessi SJ

Aims

While mechanical alignment (MA) is the traditional technique in total knee arthroplasty (TKA), its potential for altering constitutional alignment remains poorly understood. This study aimed to quantify unintentional changes to constitutional coronal alignment and joint line obliquity (JLO) resulting from MA.

Methods

A retrospective cohort study was undertaken of 700 primary MA TKAs (643 patients) performed between 2014 and 2017. Lateral distal femoral and medial proximal tibial angles were measured pre- and postoperatively to calculate the arithmetic hip-knee-ankle angle (aHKA), JLO, and Coronal Plane Alignment of the Knee (CPAK) phenotypes. The primary outcome was the magnitude and direction of aHKA, JLO, and CPAK alterations.