The Stat3 inhibitor F0648-0027 is a potential therapeutic against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a disease characterized by chronic joint inflammation, pain and joint destruction, leading to alteration in activities of daily living, yet pathological mechanisms underlying the condition are not fully clarified. To date, various therapeutic agents have been developed as RA therapy including DMARDs and/or biological agents that target inflammatory cytokines or inhibit JAK. Here we asked whether inhibiting signal transducer and activator of transcription 3 (Stat3) activity would antagonize RA. Stat3 forms dimers when activated and undergoes nuclear translocalization; thus we screened approximately 4.9 million small compounds as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening. We identified 15 as strong candidates as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening from those compounds. Four of the 15 significantly inhibited expression of IL-6 and RANKL, both of which are direct targets of Stat3, induced by IL-6. Among four, one compound, F0648-0027, significantly inhibited arthritis development without apparent adverse effects in vivo in collagen-induced arthritis model mice. F0648-0027 also significantly blocked Stat3 phosphorylation and nuclear localization following IL-6 stimulation of fibroblasts. These data suggest that Stat3 is a target for collagen-induced arthritis in mice, and that F0648-0027 could serve as a therapeutic reagent against comparable conditions in humans.

Biomechanical features of drop vertical jump are different among various sporting activities.

BACKGROUND: Risk for non-contact anterior cruciate ligament (ACL) injury can be assessed based on drop vertical jump (DVJ). However, biomechanics of DVJ may differ with various sporting activities. The purpose of the present study was to clarify whether biomechanical features of DVJ are different among various sporting activities in female athletes. METHODS: A total of 42 female athletes, including 25 basketball, 8 soccer and 9 volleyball players, participated in the current investigation. DVJ was done for each female athlete using a three-dimensional motion analysis system which consisted of six cameras, two force plates and 46 retro-reflective markers. Kinematic and kinetic data were recorded for both limbs in each athlete. Simultaneously, frontal and sagittal plane views of the DVJ were recorded using two different high-resolution video cameras to evaluate Landing Error Scoring System (LESS) score. Three-dimensional biomechanical parameters at the knee joint and LESS were compared among three different sporting activities using ANOVA or Kruskal-Wallis test after confirming normality assumption. Thereafter post hoc Tukey or Steel-Dwass was utilized for multiple comparison. RESULTS: Soccer players had better LESS score, and peak knee flexion angle was significantly larger in soccer players compared to the other sports. In addition, knee abduction angle at initial contact (IC), peak knee abduction angle, knee internal rotation angle, and knee abduction moment within 40 ms from IC were significantly smaller in soccer players, compared to basketball players. In terms of volleyball players, knee abduction angle at IC and knee internal rotation angle at IC were significantly larger than soccer players, whereas no significant biomechanical differences were found between basketball and volleyball players. CONCLUSIONS: From the present study, female basketball and volleyball players have worse LESS score, smaller peak knee flexion angle, greater knee abduction angle at IC and greater knee internal rotation angle at IC, compared to female soccer players. Thus, female basketball and volleyball players may have an increased risk of non-contact ACL injury during the jump-landing task, compared to soccer players. Biomechanics of DVJ depends on characteristics of the athlete's primary sport.

Increase in tibial internal rotation due to weight-bearing is a key feature to diagnose early-stage knee osteoarthritis: a study with upright computed tomography.

BACKGROUND: The classification of knee osteoarthritis is an essential clinical issue, particularly in terms of diagnosing early knee osteoarthritis. However, the evaluation of three-dimensional limb alignment on two-dimensional radiographs is limited. This study evaluated the three-dimensional changes induced by weight-bearing in the alignments of lower limbs at various stages of knee osteoarthritis. METHODS: Forty five knees of 25 patients (69.9 ± 8.9 years) with knee OA were examined in the study. CT images of the entire leg were obtained in the supine and standing positions using conventional CT and 320-row detector upright CT, respectively. Next, the differences in the three-dimensional alignment of the entire leg in the supine and standing positions were obtained using 3D-3D surface registration technique, and those were compared for each Kellgren-Lawrence grade. RESULTS: Greater flexion, adduction, and tibial internal rotation were observed in the standing position, as opposed to the supine position. Kellgren-Lawrence grades 1 and 4 showed significant differences in flexion, adduction, and tibial internal rotation between two postures. Grades 2 and 4 showed significant differences in adduction, while grades 1 and 2, and 1 and 3 showed significant differences in tibial internal rotation between standing and supine positions. CONCLUSIONS: Weight-bearing makes greater the three-dimensional deformities in knees with osteoarthritis. Particularly, greater tibial internal rotation was observed in patients with grades 2 and 3 compared to those with grade 1. The greater tibial internal rotation due to weight-bearing is a key pathologic feature to detect early osteoarthritic change in knees undergoing osteoarthritis.

Knee varus alters three-dimensional ankle alignment in standing- a study with upright computed tomography.

BACKGROUND: For knee osteoarthritis (OA) treatment, it is important to correct the lower limb alignment including the foot. However, in the upright position, lower limb alignment is generally assessed from the body surface or radiographs, and it is a challenge to capture the exact characteristics of three-dimensional lower limb alignment. The purpose of the study was to measure lower limb alignment in patients with knee OA using upright computed tomography (CT) and radiography, and to identify features of knee joint deformity. METHODS: A total of 45 limbs in 25 patients with knee OA were enrolled. The subjects underwent both upright CT and radiography for the whole lower limb in the standing position. The joint angles were calculated on both images. The degree of knee OA was classified according to Kellgren-Lawrence (KL) grade by referring to radiography, which is mainly based on the degree of articular cartilage loss and severity of osteophytes, and the characteristics or correlation between knee and ankle joint in each group was investigated. RESULTS: In KL-I, there was an association between varus of the knee joint and internal rotation of the talocrural joint (r = 0.76, P < 0.05). In KL-II, there was an association between varus of the knee joint and eversion of the subtalar joint (r = 0.63, P < 0.05) and talocrural joint (r = - 0.65, P < 0.05). In KL-III, there was an association between varus of the knee joint and internal rotation of the subtalar joint (r = - 0.62, P < 0.05), and in KL-IV, there was an association between varus of the knee joint and internal rotation of the subtalar joint (r = - 0.58, P < 0.05). CONCLUSIONS: The lower limb alignment of patients with knee OA in the standing position was found that as knee OA worsened, it became apparent that compensatory knee joint alignment depended on the ankle joint rather than the subtalar joint. The results may help in the rehabilitation of patients with knee OA, since the ankle joint alignment has a significant impact on the knee joint during coarse movements involving load.

Four-dimensional computed tomographic analysis of screw home movement in patients with anterior cruciate ligament deficient knee - a 3D-3D registration technique.

OBJECTIVE: The tibia externally rotates to the femur during the last 20° of the knee extension motion. This kinematic phenomenon is well known as screw home movement (SHM). The purpose was to clarify the SHM in anterior cruciate ligament deficient (ACLD) knee using four-dimensional computed tomography (4DCT). MATERIALS AND METHODS: Six patients with a unilateral isolated ACLD knee participated. In the static position, CT scan of the both limbs of the femur and tibia were performed. Then, 4DCT was performed around knee. In the CT gantry, subjects were positioned in supine position with 45° of knee flexion on a triangle pillow and were asked to extend the knee to full extension within 10 s on each limb. The CT data were accumulated in digital imaging and communication in medicine (DICOM) data format. From the static CT and 4DCT DICOM data, three-dimensional surfaces of the knee joint were reconstructed. The whole tibia surface was matched into the partial tibia surface of that frame using 3D-3D registration technique. After the assessment of coordination system of the whole leg, knee flexion, abduction, and external rotation angle were calculated. RESULTS: Knee external rotation angle was significantly smaller on the ACLD side than on the contralateral unaffected side in 0-15° of knee flexion (P < 0.05 in 0, 5, 10, and 15 degrees), while the angle was similar during 15-60° of knee flexion. CONCLUSION: The absence of SHM in ACLD knee was detected using 3D-3D registration technique based on 4DCT.

Synoviolin is not a pathogenic factor for auto-inflammatory diseases.

Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox'd mice to yield hIL-1 cTg/Synoviolin cKO mice. Synoviolin gene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.

Influence of Patella thickness on Patellofemoral pressure in total knee Arthroplasty.

BACKGROUND: Patellofemoral complications are one of the major issues after total knee arthroplasty (TKA). Excessive patellofemoral joint pressure is associated with complications after TKA surgery, and the amount of patellar osteotomy has a direct effect on patellofemoral joint pressure. The purpose of this study was to evaluate the influence of patella thickness on patellofemoral pressure in TKA. METHODS: Five freshly frozen cadavers were operated with a custom-made Stryker posterior stabilizing type knee joint prosthesis. Patellofemoral joint pressure was measured using a pressure sensor, with the knee joint flexed from 90 to 110 degrees, and with patellar thickness of - 2 mm to + 4 mm. RESULTS: Increasing or decreasing patellar thickness significantly increased or decreased patellofemoral pressure. Regarding knee flexion angle, patellofemoral pressure increased with increasing patellar thickness at all flexion angles, but the pressure increase was greatest at 90 degrees of knee flexion and smallest at 110 degrees. CONCLUSIONS: The amount of patellar osteotomy influences the patellofemoral pressure. Surgeons should avoid increasing patella thickness, since the resulting increased patellofemoral pressure may reduce knee joint function.

Compressive mechanical stress enhances susceptibility to interleukin-1 by increasing interleukin-1 receptor expression in 3D-cultured ATDC5 cells.

BACKGROUND: Mechanical overload applied on the articular cartilage may play an important role in the pathogenesis of osteoarthritis. However, the mechanism of chondrocyte mechanotransduction is not fully understood. The purpose of this study was to assess the effects of compressive mechanical stress on interleukin-1 receptor (IL-1R) and matrix-degrading enzyme expression by three-dimensional (3D) cultured ATDC5 cells. In addition, the implications of transient receptor potential vanilloid 4 (TRPV4) channel regulation in promoting effects of compressive mechanical loading were elucidated. METHODS: ATDC5 cells were cultured in alginate beads with the growth medium containing insulin-transferrin-selenium and BMP-2 for 6 days. The cultured cell pellet was seeded in collagen scaffolds to produce 3D-cultured constructs. Cyclic compressive loading was applied on the 3D-cultured constructs at 0.5 Hz for 3 h. The mRNA expressions of a disintegrin and metalloproteinases with thrombospondin motifs 4 (ADAMTS4) and IL-1R were determined with or without compressive loading, and effects of TRPV4 agonist/antagonist on mRNA expressions were examined. Immunoreactivities of reactive oxygen species (ROS), TRPV4 and IL-1R were assessed in 3D-cultured ATDC5 cells. RESULTS: In 3D-cultured ATDC5 cells, ROS was induced by cyclic compressive loading stress. The mRNA expression levels of ADAMTS4 and IL-1R were increased by cyclic compressive loading, which was mostly prevented by pyrollidine dithiocarbamate. Small amounts of IL-1ß upregulated ADAMTS4 and IL-1R mRNA expressions only when combined with compressive loading. TRPV4 agonist suppressed ADAMTS4 and IL-1R mRNA levels induced by the compressive loading, whereas TRPV4 antagonist enhanced these levels. Immunoreactivities to TRPV4 and IL-1R significantly increased in constructs with cyclic compressive loading. CONCLUSION: Cyclic compressive loading induced mRNA expressions of ADAMTS4 and IL-1R through reactive oxygen species. TRPV4 regulated these mRNA expressions, but excessive compressive loading may impair TRPV4 regulation. These findings suggested that TRPV4 regulates the expression level of IL-1R and subsequent IL-1 signaling induced by cyclic compressive loading and participates in cartilage homeostasis.

Differences of tensile strength in knot tying technique between orthopaedic surgical instructors and trainees.

BACKGROUND: Knot tying technique is an extremely important basic skill for all surgeons. Clinically, knot slippage or suture breakage will lead to wound complications. Although some previous studies described the knot-tying technique of medical students or trainees, little information had been reported on the knot-tying technique of instructors. The objective of the preset study was to assess surgeons' manual knot tying techniques and to investigate the differences of tensile strength in knot tying technique between surgical instructors and trainees. METHODS: A total of 48 orthopaedic surgeons (postgraduate year: PGY 2-18) participated. Surgeons were requested to tie surgical knots manually using same suture material. They were divided into two groups based on each career; instructors and trainees. Although four open conventional knots with four throws were chosen and done with self-selected methods, knot tying practice to have the appropriate square knots was done as education only for trainees before the actual trial. The knots were placed over a 30 cm long custom made smooth polished surface with two cylindrical rods. All knots were tested for tensile strength using a tensiometer. The surgical loops were loaded until the knot slipped or the suture broke. The tensile strength of each individual knot was defined as the force (N) required to result in knot failure. Simultaneously, knot failure was evaluated based on knot slippage or suture rupture. In terms of tensile strength or knot failure, statistical comparison was performed between groups using two-tailed Mann-Whitney U test or Fisher exact probability test, respectively. RESULTS: Twenty-four instructors (PGY6-PGY18) and 24 trainees (PGY2-PGY5) were enrolled. Tensile strength was significantly greater in trainees (83.0 ± 27.7 N) than in instructors (49.9 ± 34.4 N, P = 0.0246). The ratio of slippage was significantly larger in instructors than in trainees (P < 0.001). Knot slippage (31.8 ± 17.7 N) was significantly worse than suture rupture (89.9 ± 22.2 N, P < 0.001) in tensile strength. CONCLUSIONS: Mean tensile strength of knots done by trainees after practice was judged to be greater than that done by instructors in the present study. Clinically, knot slippage can lead to wound dehiscence, compared to suture rupture.

Estimation of the External Knee Adduction Moment during Gait Using an Inertial Measurement Unit in Patients with Knee Osteoarthritis.

Although the external knee adduction moment (KAM) during gait was shown to be a quantitative parameter of medial knee osteoarthritis (OA), it requires expensive equipment and a dedicated large space to measure. Therefore, it becomes a major reason to limit KAM measurement in a clinical environment. The purpose of this study was to estimate KAM using a single inertial measurement unit (IMU) during gait in patients with knee OA. A total of 22 medial knee OA patients (44 knee joints) performed conventional gait analysis using three-dimensional (3D) motion capture system. At the same time, we attached commercial IMUs to six body segments (sternum, pelvis, both thighs, and both shanks), and IMU signals during gait were recorded synchronized with the motion capture system. The peak-to-peak difference of acceleration in the lateral/medial axis immediately after heel contact was defined as the thrust acceleration (TA). We hypothesized that TA would represent the lateral thrust of the knee during the stance phase and correlate with the first peak of KAM. The relationship between the peak KAM and TA of pelvis (R = 0.52, p < 0.001), shanks (R = 0.57, p < 0.001) and thighs (R = 0.49, p = 0.001) showed a significant correlation. The root mean square error (RMSE) of linear regression models of pelvis, shanks, and thighs to estimate KAM were 0.082, 0.079, and 0.084 Nm/(kg·m), respectively. Our newly established parameter TA showed a moderate correlation with conventional KAM. The current study confirmed our hypothesis that a single IMU would predict conventional KAM during gait. Since KAM is known as an indicator for prognosis and severity of knee OA, this new parameter has the potential to become an accessible predictor for medial knee OA instead of KAM.

Radiographic evaluation of patellofemoral alignment in kinematically aligned total knee arthroplasty: A comparative study with mechanically aligned total knee arthroplasty.

BACKGROUND: Kinematically aligned total knee arthroplasty (KA-TKA), in which femoral component is placed 3-5° of internal rotation relative to mechanically aligned (MA)-TKA, may have a potential risk of patellofemoral malalignment. This study aimed to assess patellofemoral alignment and compare the data between KA-TKA and MA-TKA, and the relationship with patellofemoral radiographic parameters and patient reported outcomes. METHODS: Among patients who underwent TKA in 2015 and 2016 in our institute, 28 KA-TKAs with a metal-backed patellar component were retrospectively assessed for patellofemoral alignment, and 28 MA-TKAs with a metal-backed patellar component served as controls. A year postoperatively, patellar tilt and shift at 30°, 60°, and 90° knee flexion were measured on Merchant views and compared between the two TKAs. Implant positioning in each patient was assessed based on preoperative CT images and correlations of femoral component positioning with patellar tilt/shift were assessed. RESULTS: Patellar shift at 30° flexion was significantly greater in KA-TKA than in MA-TKA (p = 0.04), whereas patellar tilt angle was comparable between the two TKAs. No statistical correlation was evident between femoral component positioning and patellar shift/tilt, regardless of knee flexion angle in the two TKAs. Knee Society Score 2011 at 1 year follow-up was comparable in all subcategories between the two TKAs. CONCLUSION: Radiographic analysis of KA-TKA revealed lateral shift of the patella at 30° knee flexion at 1 year postoperatively, however patients with patellar shift were asymptomatic. Further long-term observation is required to examine the impact of KA-TKA on the patellofemoral complication.

Who Will Benefit From Kinematically Aligned Total Knee Arthroplasty? Perspectives on Patient-Reported Outcome Measures.

BACKGROUND: Indications for kinematically aligned total knee arthroplasty (KA-TKA) have remained contentious. This study aimed at exploring preoperative characteristics of patients who were suitable for and benefited from KA-TKA, based on the assessment of patient-reported outcome measures (PROMs). METHODS: Subjects comprised 100 patients undergoing KA-TKA and 100 patients undergoing mechanically aligned (MA)-TKA due to end-stage osteoarthritis. Bone cuts were performed using portable navigation systems according to 3D planning data from computed tomography. At 2 years postoperatively, all 200 patients were assessed for PROMs, including Knee Society Score 2011, pain catastrophizing scale, and pain DETECT score. Multiple regression analysis was performed with activity subscore set as a dependent variable. Principal component analysis was used to evaluate patient satisfaction and function components transformed from the 3 PROMs and to compare these components between KA-TKA and MA-TKA. RESULTS: Male gender or use of KA technique positively affected advanced activity score, whereas age, body mass index, preoperative pain DETECT score, and preoperative femorotibial angle showed negative effects. In principal component analysis, 38 KA-TKA patients achieved a higher function score, with satisfaction scores comparable to those from MA-TKA. These 38 patients were characterized by a higher percentage of males, younger age, and higher preoperative total activity score. CONCLUSION: From the perspective of PROMs, KA-TKA should be favored over MA-TKA for young active males, because these patient groups achieved higher functional activity when undergoing KA-TKA.

Effects of Toe Direction on Biomechanics of Trunk, Pelvis, and Lower-Extremity During Single-Leg Drop Landing.

CONTEXT: Toe direction is an important factor affecting knee biomechanics during various movements. However, it is still unknown whether toe direction will affect trunk and pelvic movements. OBJECTIVE: To examine and clarify the effects of toe directions on biomechanics of trunk and pelvis as well as lower-extremities during single-leg drop landing (SLDL). DESIGN: Descriptive laboratory study. SETTING: Research laboratory. PARTICIPANTS: A total of 27 male recreational-level athletes. INTERVENTION(S): Subjects performed SLDL under 3 different toe directions, including 0° (toe neutral), 20° (toe-in [TI]), and -20° (toe-out). SLDL was captured using a motion analysis system. Nondominant leg (27 left) was chosen for the analysis. MAIN OUTCOME MEASURES: Peak values of kinematic and kinetic parameters during landing phase were assessed. In addition, those parameters at the timing of peak vertical ground reaction force were also assessed. The data were statistically compared among 3 different toe directions using 1-way repeated measures of analysis of variance or Friedman χ2 r test. RESULTS: Peak knee abduction angle and moment in TI were significantly larger than in toe neutral and toe-out (P < .001). Moreover, peak greater anterior inclination, greater inclination, and rotation of trunk and pelvis toward the nonlanding side were seen in TI (P < .001). At the timing of peak vertical ground reaction force, trunk inclined to the landing side with larger knee abduction angle in TI (P < .001). CONCLUSIONS: Several previous studies suggested that larger knee abduction angle and moment on landing side as well as trunk and pelvic inclinations during landing tasks were correlated with knee ligament injury. However, it is still unknown concerning the relationship between toe direction and trunk/pelvis movements during landing tasks. From the present study, TI during SLDL would strongly affect biomechanics of trunk and pelvis as well as knee joint, compared with toe neutral and toe-out.

Effect of body mass index on surgical times of lumbar laminoplasty and lower limb arthroplasties.

BACKGROUND: Obesity is an important factor affecting incidence and development of musculoskeletal degenerative changes. In addition, obese patients are considered less favorable surgical candidates for decompression surgery in degenerative lumbar spinal canal stenosis and lower limb arthroplasty. The purpose was to assess disease characteristics of lumbar spinal canal stenosis as well as lower limb osteoarthritis, and to investigate surgical times based on body mass index (BMI) in lumbar decompressive surgery and lower limb arthroplasties. METHODS: A total of 1161 patients with a diagnosis of lumbar canal stenosis (LCS), hip osteoarthritis (HOA) and knee osteoarthritis (KOA) were enrolled. The present investigation was conducted as a retrospective study using routinely collected data. All patients underwent primary decompressive surgery (laminoplasty: LAM) or lower limb arthroplasty (total hip arthroplasty: THA and total knee arthroplasty: TKA). All of the patients were divided into 3 groups based on BMI (kg/m2) (Group A: ≤ 24.9; Group B: 25-29.9; Group C: ≥ 30) within each disease category. To assess disease characteristics, age, gender, and BMI were evaluated for each disease category. Moreover, surgical times for LAM, THA and TKA were also assessed based on BMI classification. RESULTS: A total of 269, 470, and 422 patients were allocated to the HOA category, the KOA category, and the LCS category, respectively. The KOA category included the oldest patients and largest BMI, compared to the HOA and the LCS categories. Regarding gender difference, LCS was more common in males than in females, while opposite phenomenon was observed in the HOA and the KOA categories. The heaviest group (Group C) was significantly younger than Groups A or B in TKA and LAM. Surgical time was significantly longer in patients with overweight or obese patients than in those with normal weight in TKA and LAM, while BMI didn't affect the time in THA. CONCLUSIONS: Disease characteristics of the KOA category and the LCS category were notably affected by BMI, and surgical times in TKA and LAM were significantly longer for overweight or obese patients, whereas THA was less affected by BMI concerning disease characteristics and surgical time.

Rheumatoid Arthritis Patients Achieve Better Satisfaction but Lower Functional Activities as Compared to Osteoarthritis Patients After Total Knee Arthroplasty.

BACKGROUND: Recently, poor patient satisfaction after total knee arthroplasty (TKA) has gained attention mainly in osteoarthritis (OA) patients; however, satisfaction after TKA remains to be understood in rheumatoid arthritis (RA) patients. This study aimed to examine satisfaction and function after RA TKA using patient-reported outcome measures and to compare the results with those of OA-TKA. METHODS: This study enrolled 534 TKAs of 501 patients consisting of 75 TKAs of 70 RA patients and 459 TKAs of 431 OA patients. Data of patient-reported outcome measures such as new Knee Society Score 2011, Pain Catastrophizing Scale, and Pain DETECT Score were collected at 2 years. Multiple regression analysis was performed with Knee Society Score satisfaction score set as a dependent variable in order to clarify factors affecting patient satisfaction. Principle component analysis was performed, and satisfaction and function components were compared between RA and OA. RESULTS: All activity scores were significantly lower in RA TKA than in OA TKA, whereas the range of motion and patient satisfaction scores were significantly better in RA TKA than in OA TKA. Scores for symptom, expectation, basic activity, and discretional activity positively affected patient satisfaction (P < .001), while Pain Catastrophizing Scale negatively did (P = .021). Importantly, diagnosis of RA itself pushed up the patient satisfaction score by 1.5 points. Principle component analysis revealed that RA TKA achieved significantly higher satisfaction component (P = .001), but lower function component (P < .0001) compared to OA TKA. CONCLUSION: Patient satisfaction was better but functional activity was lower in RA than in OA. As poor functional activity was evident preoperatively in RA patients, to improve functional outcome should be future challenge for RA TKA.

Variation of three-dimensional femoral bowing and its relation to physical status and bone mineral density: a study with CT.

PURPOSE: Anatomically, the femoral bone shows sagittal and coronal bowing. Pronounced bowing would affect femoral implant surgery accuracy, but factors associated with degrees of three-dimensional (3D) femoral bowing have not yet been identified. This study measured 3D femoral bowing and examined the correlation between 3D femoral bowing and risk factors. METHODS: 3D femoral bone models of unaffected legs from 125 patients were reconstructed from computed tomography data. A trans-epicondylar axis (TEA)-based coordinate system was introduced into bone models and the reproducibility of this coordinate system was evaluated. The cross-sectional contours of the femoral canal were extracted along the vertical axis of the TEA-based coordinate system, and the angles of 3D femoral bowing were examined. RESULTS: The reproducibility to set the coordinate was very high. Total, sagittal, and coronal femoral bowing were 8.9 ± 1.8°, 8.7 ± 1.8°, and 0.1 ± 1.9°, respectively. There was no significant difference in the degrees of femoral bowing between males and females. Total, coronal, and sagittal femoral bowing correlated with age, height, and femoral length, but only femoral coronal bowing correlated with bone mineral density (BMD) of the femur and lumbar spine. CONCLUSIONS: We introduced a highly reproducible method for measuring femoral sagittal and coronal bowing by constructing a femoral 3D coordinate system. Anterior femoral bowing was the dominant direction of bowing in our Japanese cohort, whereas the degree of lateral bowing correlated with age, height, femoral length, and BMD. Our results suggest that lateral femoral bowing could increase with aging and decreasing BMD.

Kinematically aligned total knee arthroplasty reduces knee adduction moment more than mechanically aligned total knee arthroplasty.

PURPOSE: Knee adduction moment (KAM) has been recognized as a good clinical surrogate for medial tibiofemoral joint loading and is associated with implant durability after total knee arthroplasty (TKA). This study aimed to examine the effects of joint line obliquity in kinematically aligned TKA (KA-TKA) on KAM during gait. METHODS: The study enrolled 21 knees from 18 patients who underwent cylindrical axis reference KA-TKA and a matched group of 21 knees from 18 patients who underwent mechanically aligned (MA)-TKA as controls. Gait analyses were performed the day before TKA and at an overall mean of 2.6 years postoperatively. First peak KAM and variables associated with frontal knee kinetics were determined and compared between groups. RESULTS: In KA-TKA, the proximal tibia was resected with 3.4° ± 1.5° of varus in relation to the mechanical axis, and the final femorotibial shaft axis was 176.7° ± 3.8° with KA-TKA and 174.4° ± 3.0° with MA-TKA. KAM was significantly smaller with KA-TKA than with MA-TKA (p < 0.032). Regarding variables affecting KAM, significant differences were evident between the two TKAs for knee adduction angle (p = 0.0021), lever arm (p = 0.028), and Δlever arm (p = 0.0001). CONCLUSIONS: In KA-TKA, joint line obliquity reduced peak KAM during gait, despite slight varus limb alignment, and this reduced KAM in KA-TKA can tolerate constitutional varus alignment. In clinical settings, KA-TKA thus represents a promising technical option for patients with large coronal bowing of the shaft carrying a risk of increased KAM after TKA. LEVEL OF EVIDENCE: III.

Joint Line Modification in Kinematically Aligned Total Knee Arthroplasty Improves Functional Activity but Not Patient Satisfaction.

BACKGROUND: Joint line modification in kinematically aligned total knee arthroplasty (KA-TKA) is attracting attention in expectation of optimizing patient satisfaction after TKA. This study aimed to examine the effects of joint line modification on Pain Catastrophizing Scale (PCS), painDETECT score, and new Knee Society Score (KSS) 2011, all of which are robustly related to patient satisfaction. METHODS: The study enrolled 45 knees of 45 patients undergoing KA-TKA and a matched group of 45 knees of 45 patients undergoing mechanically aligned (MA) TKA as controls. At a mean of 31.6 months after TKA, new KSS 2011, PCS, and painDETECT score were assessed and compared between KA- and MA-TKA. Data from all 90 patients were pooled into one group for secondary multiple regression analysis to identify postoperative variables affecting patient satisfaction. RESULTS: Assessment with new KSS 2011 showed no significant differences between the 2 TKAs preoperatively, but functional activity score was significantly higher with KA-TKA than with MA-TKA postoperatively (P = .047). Among the 4 categories of functional activity score, advanced activity score was significantly higher with KA-TKA than with MA-TKA (P = .003). Of the 5 advanced activities, the score for climbing ladder/step stool was significantly greater with KA-TKA (P = .004). KA-TKA failed to influence patient satisfaction score. Multiple regression analysis revealed that standard activity score and PCS affected patient satisfaction positively and negatively, respectively. CONCLUSION: Joint line modification in KA-TKA improved functional activity but not patient satisfaction. PCS was a key element negatively affecting patient satisfaction.

Comparison between cylindrical axis-reference and articular surface-reference femoral bone cut for total knee arthroplasty.

PURPOSE: Reproducing a functional flexion-extension axis (FEA) of the femur is key to achieving successful collateral ligament balance and joint line in total knee arthroplasty (TKA). This study compared the feasibility of cylindrical axis (CA)-reference bone cut and articular surface-reference bone cuts in reproducing the FEA for Japanese osteoarthritis patients. METHODS: The study enrolled 122 knees from 86 patients who underwent primary TKA due to grade III or IV osteoarthritis. Data from pre-operative CT were reconstructed into three-dimensional (3D) models using 3D-planning software. Cylindrical radii of the condyles were measured, and femoral bone cut angles relative to anatomical landmarks were determined in the coronal and axial reference planes based on CA-reference and articular surface-reference methods. RESULTS: Mean cylindrical radii for medial and lateral femoral condyles were 17.4 ± 1.6 and 17.3 ± 1.4 mm, respectively. Of the 122 knees, 46 exhibited >1 mm of difference between condyles. Fifty-three and 22 knees exhibited >2° of angular difference between CA-reference and articular surface-reference bone cuts in the coronal and axial planes. Mean angle of the CA and surgical epicondylar axis in 3D space was 4.6 ± 2.1°. As practical parameters for TKA, the angle between CA and IM rod was significantly larger than that between the distal articular surface line and IM rod in the coronal plane (p < 0.0001), indicating that CA-reference involves a smaller valgus bone cut of the distal femur than articular surface reference. CONCLUSIONS: CA-reference bone cut of the femur is preferable to articular surface-reference bone cut for reproducing FEA in Japanese OA patients, in whom more than one-third of knees exhibited asymmetry of radii between medial and lateral condyles. In clinical practice, the CA-reference bone cut represents a good technical option for kinematically aligned TKA in the Japanese population.

Mechanically aligned total knee arthroplasty carries a risk of bony gap changes and flexion-extension axis displacement.

PURPOSE: The flexion-extension axis (FEA) of the femur is substantially changed after mechanically aligned total knee arthroplasty (TKA) due to a discrepancy in bone cut thickness between the posterior and distal femoral regions. This study assessed the bony gap changes and FEA displacement caused by this problem in osteoarthritis patients. METHODS: The study enrolled 60 knees from 60 patients for whom primary TKA was planned due to medial knee osteoarthritis. All patients underwent computed tomography, and 3-dimensional (3D) bone models were reconstructed on 3D-planning software. Bone cuts of the distal femur and proximal tibia were simulated to be perpendicular to each mechanical axis. Bony gap change was computed as the difference in bone cut thickness between medial and lateral compartments. Each femoral condyle was assessed for potential FEA displacement, as the difference in bone cut thickness between posterior and distal femoral regions. RESULTS: The mean magnitude of bony gap discrepancy necessary for mediolateral balancing was 1.6 ± 3.3 mm (range -7 to 8.2 mm) at 0° extension and -0.2 ± 2.6 mm (range -6.4 to 4.3 mm) at 90° flexion. At least 2 mm of bony gap discrepancy at 0° extension and 90° flexion was found in 40 patients (67%) and 26 patients (43%), respectively. In terms of femoral bone cut, posterior bone cut thickness was significantly larger than distal bone cut thickness in the medial compartment (p < 0.001). Bony gap discrepancy between distal and posterior regions of the femoral condyle was ≥2 mm in 28 patients (47%). CONCLUSIONS: This study focused on two flaws of mechanically aligned TKA in OA patients. Substantial numbers of patients inevitably required >2 mm of medial collateral ligament release at 0° extension and showed a bone cut discrepancy between distal and posterior regions, carrying a risk of FEA displacement and subsequent unnatural knee motions during knee extension and flexion. Level of evidence IV.