Small medial proximal tibial angle is a radiographic finding strongly associated with less coronal alignment correction under valgus stress in medial knee osteoarthritis.

PURPOSE: The degree to which varus knees can be corrected manually is important when considering total versus unicompartmental knee arthroplasty (UKA). The primary aim was to clarify the relationship between the degree of coronal alignment correction and radiographic parameters involved in UKA prognosis using preoperative full-length lower extremity valgus stress radiography. The secondary aim was to identify the factors affecting alignment correction. METHODS: This retrospective observational study included 115 knees with medial osteoarthritis that underwent knee osteotomy or arthroplasty. Percent mechanical axis without valgus stress (%MA: neutral, 50%; varus, <50% and valgus, >50%), mechanical lateral distal femoral angle, lateral bowing femoral angle, medial proximal tibial angle (MPTA), joint line convergence angle, medial and lateral joint space width (LJSW) and medial femoral and tibial joint osteophyte size were measured using preoperative full-length weight-bearing radiographs. Correlation and multiple linear regression analyses were used to assess associations between parameters and %MA with valgus stress or amount of %MA change (%MA with valgus stress minus %MA without valgus stress). RESULTS: %MA with valgus stress was correlated with all radiographic parameters. %MA change was correlated with parameters except for MPTA and LJSW. Multiple regression analyses showed that %MA without valgus stress and MPTA were associated with both %MA with valgus stress and %MA change. When %MA with valgus stress was set at 30%, 40% and 50%, MPTA cutoff values were 81.6°, 83.5° and 84.9°, and cutoffs for %MA without valgus stress were 10.7%, 17.1% and 25.1%, respectively. CONCLUSION: Small MPTA is strongly associated with less alignment correction under valgus stress in varus knees. The finding is useful in surgical planning, especially to avoid undercorrection with UKA when valgus stress radiographs are unavailable. LEVEL OF EVIDENCE: Level III.

Predictors for the Knee Extension Strength at 2 Yrs After Total Knee Arthroplasty Using Regression Tree Analysis.

OBJECTIVE: The aim of the study is to clarify the interactive combinations of clinical factors associated with knee extension strength 2 yrs after total knee arthroplasty. DESIGN: A retrospective cohort study was conducted on 264 patients who underwent total knee arthroplasty. Knee extension strength was assessed preoperatively, 3 wks, and 2 yrs after total knee arthroplasty. Physical functions were measured with 10-m walking test, Timed Up and Go test, one-leg standing time, isometric knee flexion strength, knee joint stability, knee pain, femora-tibial angle, and passive knee extension and flexion angle before surgery as a baseline and 3 wks after total knee arthroplasty as acute phase. Regression tree analysis was conducted to clarify the interactive combinations that accurately predict the knee extension strength 2 yrs after total knee arthroplasty. RESULTS: Operational side knee extension strength (>1.00 Nm/kg) at acute phase was the primal predictor for the highest knee extension strength at 2 yrs after total knee arthroplasty. Acute phase Timed Up and Go test (≤10.13 secs) and baseline 10-m walking test (≤11.72 secs) was the second predictor. Acute phase nonoperative side knee extension strength (>0.90 Nm/kg) was also selected as the predictor. CONCLUSIONS: This study demonstrated that knee extension strength or Timed Up and Go test in the acute phase and 10-m walking test before total knee arthroplasty are useful for estimating the knee extension strength after total knee arthroplasty. The results will help determine specific postoperative rehabilitation goals and training options.

Catastrophic Mid-Flexion Instability After Avulsion Fractures of the Articular Capsule of the Femur and Tibia in a Patient With Posterior-Stabilized Total Knee Arthroplasty: A Case Report.

Mid-flexion instability can be caused by patient-related, implant-related, or technique-specific factors and impairs the activities of daily living after total knee arthroplasty (TKA). In this study, we report a rare case of a patient with severe mid-flexion instability following tibial and femoral avulsion fractures after posterior-stabilized (PS) TKA for knee osteoarthritis. An 82-year-old female with bilateral knee osteoarthritis underwent staged bilateral TKA with a posterior-stabilized prosthesis. The course of the early postoperative period was good, and the patient was able to walk independently with a cane. Two months postoperatively, the patient fell and then experienced left knee pain and instability in the mid-flexion range. Radiographic images showed avulsion fractures of the articular capsule of the femur and tibia, and fluoroscopic examination showed severe posterior subluxation of the tibia between 40° and 60° of flexion. Conservative treatment with a functional knee brace and quadriceps training was initiated due to the patient's hesitation to undergo a second surgery; however, no improvement was observed. Eventually, revision surgery was planned three months after the fall incident (five months after the left primary TKA). At revision surgery, osteosynthesis of the tibial avulsion fracture and thickening of the PS insert did not sufficiently stabilize the instability, and revision TKA with a rotating-hinge prosthesis was needed. The postoperative course was uneventful, and she was able to walk with a cane within two weeks after revision TKA with no complaints of instability. Two years postoperatively, the patient recovered well and had no recurrence of instability, pain, or dysfunction. This case report shows that loss of support by the joint capsules due to avulsion fractures may cause significant anteroposterior instability in the mid-flexion position after posterior-stabilized TKA. In such a case, conservative treatment failed, and the revision of the rotating-hinge prosthesis provided stability and good improvement.

Development of a novel model for intraarticular adhesion in rat knee joint.

In this study, a novel rat model of knee joint adhesion was developed, and its formation was analyzed quantitatively over time. Thirty-nine Wistar rats were randomly divided into intact control (n = 3) and experimental (n = 36) groups. The latter was equally divided into three groups according to the experimental intervention: fixed with deep bending of the knee joint (group I), fixed after incision of the capsule (group II), and fixed after exposure of the patellofemoral joint to artificial patellar subluxation (group III). All rats were subdivided according to their joint immobilization period (1, 2, or 4 weeks). Thereafter, the limited range of motion of the knee joint with (limited knee range of motion) and without (limited knee joint intrinsic range of motion) skin and muscles were measured. The lengths of adhesions of the anterior knee joint and posterior capsules were evaluated histologically. The limited intrinsic range of motion of the knee joint was found to be increased in groups II and III compared to that in group I 4 weeks after immobilization. Adhesions were confirmed within 1 week after immobilization in groups II and III. The length of the adhesions in group III was significantly longer than in other groups at 2 weeks and remained longer than in group I at 4 weeks. This model may contribute to the assessment of the adhesion process and development of new therapeutic avenues following trauma or surgical invasion.

Identification of anti-citrullinated osteopontin antibodies and increased inflammatory response by enhancement of osteopontin binding to fibroblast-like synoviocytes in rheumatoid arthritis.

BACKGROUND: Anti-citrullinated protein/peptide antibodies (ACPAs) are present in patients at onset and have important pathogenic roles during the course of rheumatoid arthritis (RA). The characteristics of several molecules recognized by ACPA have been studied in RA, but the positivity rate of autoantibodies against each antigen is not high, and the pathogenic mechanism of each antibody is not fully understood. We investigated the role of anti-citrullinated osteopontin (anti-cit-OPN) antibodies in RA pathogenesis. METHODS: Enzyme-linked immunosorbent assays on RA patients' sera were used to detect autoantibodies against OPN. Fibroblast-like synoviocytes (FLS) isolated from RA patients were used to test the binding activity and inflammatory response of OPN mediated by anti-cit-OPN antibodies, and their effect was tested using an inflammatory arthritis mouse model immunized with cit-OPN. Anti-cit-OPN antibody positivity and clinical characteristics were investigated in the patients as well. RESULTS: Using sera from 224 RA patients, anti-cit-OPN antibodies were positive in approximately 44% of RA patients, while approximately 78% of patients were positive for the cyclic citrullinated peptide (CCP2) assay. IgG from patients with anti-cit-OPN antibody increased the binding activity of OPN to FLSs, which further increased matrix metalloproteinase and interleukin-6 production in TNF-stimulated FLSs. Mice immunized with cit-OPN antibodies experienced severe arthritis. Anti-cit-OPN antibodies in RA patients decreased the drug survival rate of tumor necrosis factor (TNF) inhibitors, while it did not decrease that of CTLA4-Ig. CONCLUSIONS: Anti-cit-OPN antibodies were detected in patients with RA. IgG from patients with anti-cit-OPN antibodies aggravated RA, and anti-cit-OPN antibody was a marker of reduced the survival rate of TNF inhibitors in RA patients.

Interactive Combinations Between Gait Speed and Physical Function at Acute Phase Can Predict the Physical Activity at 2 Years After Total Knee Arthroplasty Using Classification and Regression Tree Analysis.

OBJECTIVE: To clarify the interactive combinations of various clinical factors associated with physical activity (PA) at 2 years after total knee arthroplasty (TKA) using classification and regression tree (CART) analysis. DESIGN: A retrospective cohort study. SETTING: A single university hospital. PARTICIPANTS: 286 patients who underwent TKA (N=286). MAIN OUTCOME MEASURES: PA was assessed preoperatively, 3 weeks, and 2 years after TKA. Physical functions, namely, 10 m walking test (10MWT), timed Up and Go test, 1-leg standing time, isometric knee extension and flexion strength, knee joint stability, knee pain, femora-tibial angle, and the passive knee extension and flexion angle, were measured before surgery as a baseline and 3 weeks after TKA as acute phase. CART analysis was conducted to clarify the interactive combinations that accurately predict the PA at 2 years after TKA. RESULTS: The results of CART analysis indicated that gait speed (≥1.05 m/s) at the acute phase after TKA was the primal predictor for the postoperative PA at 2 years. The highest postoperative PA at 2 years was determined by gait speed (≥1.05 m/s) and PA (>74.5) at the acute phase. The PA at baseline and at acute phase, as well as the body mass index were also selected as predictors of postoperative PA at 2 years. CONCLUSION: The present study suggested that acquiring gait speed (≥1.05 m/s) and PA (>74.5) in the postoperative acute phase is the predictive of a high PA at 2 years after TKA.

Femoral bowing affects varus femoral alignment but not patient satisfaction in mechanically aligned total knee arthroplasty.

PURPOSE: This study evaluated whether patients with particular lower limb morphological factors have femoral and tibial component malpositioning during mechanically aligned total knee arthroplasty (TKA) and lower postoperative satisfaction. METHODS: This study included 146 knees in 117 Asian patients undergoing TKA for medial osteoarthritis. Preoperative bony morphological factors such as the angle between the femoral mechanical and anatomical axes (MA-AA angle), angle between the anatomical axes of the proximal and distal femur (lateral bowing femoral angle, LBFA), mechanical lateral distal femoral angle, medial proximal tibial angle, and % anatomical axis of the tibia were evaluated, as well as preoperative and 1-year postoperative 2011 Knee Society scores (KSSs). RESULTS: MA-AA angle and LBFA were significantly larger in knees with varus femoral component alignment versus neutral alignment. Preoperative MA-AA angle was underestimated in patients with larger MA-AA angle or LBFA, especially by inexperienced surgeons. Tibial morphological factors did not affect tibial component alignment. Changes in 2011 KSSs were similar among groups by lower limb alignment or femoral and tibial component alignment. CONCLUSION: Femoral bowing affects varus femoral component alignment by obscuring preoperative planning, but it had little impact on patient satisfaction when mechanical alignment is targeted during TKA.

Anteromedial Tibial Attachment in Single-Bundle Anterior Cruciate Ligament Reconstruction Can Represent Normal Kinematics in Computer Simulation.

Tunnel position during anterior cruciate ligament (ACL) reconstruction is considered as an important factor to restore normal knee kinematics and to gain better clinical outcomes. It is still unknown where the optimal femoral and tibial tunnel position is located in single-bundle (SB) ACL reconstruction. The purposes of this study were to analyze the knee kinematics with various graft positions and to propose the optimal graft position during SB ACL reconstruction. A musculoskeletal computer simulation was used to analyze knee kinematics. Four attachments on the femoral side (anteromedial [AM], mid, posterolateral [PL], and over-the-top positions) and three attachments on the tibial side (AM, middle, and PL positions) were determined. The middle-bundle attachment was placed at the midpoint of the AM and PL bundle attachments for the femoral and tibial attachments. SB ACL reconstruction models were constructed to combine each of the four femoral attachments with each of three tibial attachments. Kinematic comparison was made among a double-bundle (DB) model and 12 SB reconstruction models during deep knee bend and stair descent activity. The tunnel position of the tibia had greater effect of knee kinematics than that of the femur. AM tibial attachment models showed similar medial and lateral anteroposterior positions to the DB model for both activities. Axial rotation in the AM tibial attachment models was similar to the DB model regardless of the femoral attachment, whereas greater maximum axial rotation was exhibited in the PL tibial attachment models, especially during stair descent activity. AM tibial attachment can represent normal knee kinematics, whereas the PL tibial attachment can induce residual rotational instability during high-demand activities. The AM tibial tunnel is recommended for SB ACL reconstruction.

Biomechanical Comparison of Kinematic and Mechanical Knee Alignment Techniques in a Computer Simulation Medial Pivot Total Knee Arthroplasty Model.

Several concepts may be used to restore normal knee kinematics after total knee arthroplasty. One is a kinematically aligned (KA) technique, which restores the native joint line and limb alignment, and the other is the use of a medial pivot knee (MPK) design, with a ball and socket joint in the medial compartment. This study aimed to compare motions, contact forces, and contact stress between mechanically aligned (MA) and KA (medial tilt 3° [KA3] and 5° [KA5]) models in MPK. An MPK design was virtually implanted with MA, KA3, and KA5 in a validated musculoskeletal computer model of a healthy knee, and the simulation of motion and contact forces was implemented. Anteroposterior (AP) positions, mediolateral positions, external rotation angles of the femoral component relative to the tibial insert, and tibiofemoral contact forces were evaluated at different knee flexion angles. Contact stresses on the tibial insert were calculated using finite element analysis. The AP position at the medial compartment was consistent for all models. From 0° to 120°, the femoral component in KA models showed larger posterior movement at the lateral compartment (0.3, 6.8, and 17.7 mm in MA, KA3, and KA5 models, respectively) and larger external rotation (4.2°, 12.0°, and 16.8° in the MA, KA3, and KA5 models, respectively) relative to the tibial component. Concerning the mediolateral position of the femoral component, the KA5 model was positioned more medially. The contact forces at the lateral compartment of all models were larger than those at the medial compartment at >60° of knee flexion. The peak contact stresses on the tibiofemoral joint at 90° and 120° of knee flexion were higher in the KA models. However, the peak contact stresses of the KA models at every flexion angle were <20 MPa. The KA technique in MPK can successfully achieve near-normal knee kinematics; however, there may be a concern for higher contact stresses on the tibial insert.

Static Mediolateral Tilt of the Joint Line after Total Knee Arthroplasty Does Not Reflect Dynamic Tilt during a Stair Ascent Activity.

The correlation between static and dynamic mediolateral (ML) tilts of the joint line in the coronal plane remains unknown after total knee arthroplasty (TKA). The purpose was to evaluate the ML tilt as measured by two-dimensional to three-dimensional registration during stair ascent in TKA patients, and to examine the correlation between the dynamic ML tilt and radiographic measurements of static indices. Thirty-two knees that underwent TKA using the mechanical alignment method were included. Continuous sagittal fluoroscopy was taken from before initial contact (IC) until after the toe-off (TO) phase during the stair ascent. The ML tilt of the tibial component relative to the ground was analyzed in terms of dynamic alignment using image-matching techniques, whereas static alignment was measured using standing long-leg radiographs. The correlation between static and dynamic ML tilts was evaluated. In the fluoroscopic analysis, the joint line was neutral (0.0 degree, standard deviation [SD] = 3.4 degrees) around IC phases, then was tilted valgus (5.5° valgus, SD = 2.6 degrees) in the mid-stance (MS) phase. After the TO phase, the joint line became almost neutral (0.4 degrees valgus, SD = 3.1 degrees). The dynamic ML tilt was significantly more varus during the IC phase and significantly more valgus in MS and TO phases than the static ML tilt (1.4 degrees valgus, SD = 2.0 degrees). No correlation was found between static and dynamic ML tilts in weight-bearing phases. During stair ascent, the static tilt had no correlation with the dynamic tilt in weight-bearing phases despite being in the same range. Static lower limb alignment does not reflect coronal alignment during motion. Further research should be conducted to determine whether the horizontal dynamic ML tilt can improve long-term durability and clinical outcomes after TKA.

Hinge fractures reaching the tibial plateau can be caused by forcible opening of insufficient posterior osteotomy during open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to use the finite element method (FEM) to reproduce fracture lines that reach the lateral tibial plateau during open-wedge high tibial osteotomy (OWHTO) in patients with Type III lateral hinge fracture (LHF). It was hypothesized that the FEM could clarify biomechanical causes of Type III LHF, enabling prevention of adverse complications. METHODS: This study used the nonlinear FEM to analyze the data of eight knees in eight patients (two males and six females) with Type III LHF among 82 patients who underwent OWHTO, as well as the data of eight individuals with no LHF. To predict the onset of Type III LHF, simulation models were also developed in which posterior osteotomy sufficiency varied from 50% to perfect, the latter defined as osteotomy reaching the hinge point. RESULTS: Real-life instances of Type III LHF caused by insufficient posterior osteotomy were reproduced in all patient-specific FEM models, and these models accurately predicted fracture types and locations. During opening of the osteotomy gap, the fracture line reached the lateral tibial plateau, and extended vertically from the end of the insufficient posterior osteotomy, avoiding the rigid proximal tibiofibular joint. In contrast, sufficient posterior osteotomy resulted in a lack of LHF. Posterior osteotomy extension ≥ 70% of the width of the osteotomy plane was the cut-off value to prevent Type III LHF. CONCLUSION: Forced opening of insufficient posterior osteotomy was found to be a biomechanical cause of Type III LHF that extended perpendicularly to the lateral tibial plateau, avoiding the proximal tibiofibular joint. The clinical significance of this study is that sufficient posterior osteotomy during OWHTO, defined as at least 70% of the width of the osteotomy plane, can prevent Type III LHF.

Knee Alignment Correction by High Tibial Osteotomy Reduces Symptoms and Synovial Inflammation in Knee Osteoarthritis Accompanied by Macrophage Phenotypic Change From M1 to M2.

OBJECTIVE: This study aimed to determine whether alignment correction by high tibial osteotomy (HTO) can change the biologic intraarticular microenvironment of osteoarthritic (OA) knees. METHODS: Synovial tissue (ST) and fluid (SF) were collected from the affected knees of 31 OA patients during initial HTO and plate removal surgeries. Changes in gene expression in ST were investigated by microarray and real-time polymerase chain reaction (PCR). ST specimens were also evaluated histologically using synovitis scores and immunofluorescence staining to determine macrophage polarity. Cytokines and chemokines in SF were analyzed by enzyme-linked immunosorbent assays. The mechanism of macrophage polarization was investigated in human peripheral blood mononuclear cell-derived macrophages and fibroblast-like synoviocytes (FLS) stimulated with cartilage fragments. We also evaluated Spearman correlations between Knee Injury and Osteoarthritis Outcome scores (KOOS) and macrophage-related gene expression. RESULTS: The microarray results indicated down-regulated inflammatory genes and pathways. Real-time PCR determined that genes expressing proinflammatory IL1B and IL6 were down-regulated and M2 macrophage-related IL1RA, IL10, CCL18, and CD206 were up-regulated. Histologic findings revealed attenuated synovitis scores and a shift from M1 to M2 macrophages. Interleukin-1ß (IL-1ß) concentrations in SF decreased after HTO. Cartilage fragments were responsible for M1 macrophage polarization and proinflammatory gene and protein expression in macrophages, whereas cartilage fragments up-regulated only IL-6 protein in FLS. Postoperative KOOS positively correlated with the expression of the M2-related genes CCL18 and CD206. CONCLUSION: Correction of lower limb alignment with HTO attenuated synovial inflammation and changed macrophage polarization from M1 to M2, suggesting an improved intraarticular environment in knee OA.

Larger bone marrow lesion volume before medial open-wedge high tibial osteotomy correlates with better improvement of clinical scores in patients with knee osteoarthritis.

PURPOSE: This study evaluated the clinical outcomes of medial open-wedge high tibial osteotomy (MOWHTO) and bone marrow lesion (BML) scores and volumes. The hypotheses were that quantitative BML volume is more associated with clinical outcomes of MOWHTO than qualitative BML evaluations, and pre-operative BML volume is associated with the improvement of clinical outcomes. METHODS: Patients who underwent MOWHTO were retrospectively enrolled. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was recorded before the initial surgery and at plate removal surgery. Using pre-operative short-time inversion recovery magnetic resonance imaging, BMLs were evaluated using three qualitative scores, reflecting the maximum length, proportion, and intensity of BML. For quantification, BMLs of the femur and tibia were separately defined as lesions with a threshold greater than the mean signal intensity plus two standard deviations, using the corresponding lateral condyles as controls. The association between the KOOS scales and BML scores/volume was evaluated using Spearman's correlation coefficient. Multivariate linear regression analyses for post-operative KOOS scales were performed using the tibial BML volume as one of the four independent variables. RESULTS: The final analysis included 40 MOWHTO cases. Two qualitative BML scores correlated only with pre-operative KOOS sports. Femoral and tibial BML volumes were correlated with post-operative KOOS QOL (ρ = 0.40, p = 0.01) and sports (ρ = 0.36, p = 0.02), respectively. Tibial BML volume was significantly correlated with all five delta KOOS scales (ρ = 0.39-0.51, p = 0.01-0.001), however, femoral BML volume was only correlated with delta KOOS QOL (ρ = 0.41, p = 0.01). In multivariate analyses, tibial BML volume was a significant positive predictor for every post-operative KOOS scale, while post-operative % mechanical axis was also a positive significant variable, except post-operative KOOS pain. CONCLUSION: Tibial BML volume was positively correlated with one post-operative KOOS scale and all delta KOOS scales. A larger pre-operative tibial BML and appropriate alignment correction were associated with a better post-operative KOOS scales. Pre-operative large BML had no negative influence on post-operative clinical outcomes; hence, surgeons need not hesitate to perform MOWHTO in patients with large BMLs in the medial condyles. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Mosaicplasty With High Tibial Osteotomy for Knee Subchondral Insufficiency Fracture Had Better Magnetic Resonance Observation of Cartilage Repair Tissue Scores With Less Bone Marrow Edema and Better Plug Union and Less Plug Necrosis Compared With Mosaicplasty Alone.

PURPOSE: To determine the magnetic resonance imaging (MRI) findings after mosaicplasty (MOS) for knee subchondral insufficiency fracture (SIFK), and to analyze the relationship between MRI findings and clinical outcomes. METHODS: We retrospectively reviewed the cases of consecutive patients who underwent MOS for SIFK with/without high tibial osteotomy (HTO) between January 1998 and December 2015. The MRI findings at 12 months after the surgery were assessed by the modified magnetic resonance observation of cartilage repair tissue (MOCART) score to determine the degree of bone marrow edema (BME), plug union, and plug necrosis. The clinical outcomes were assessed by Lysholm score to clarify the minimal clinically important difference (MCID) and patient acceptable symptom state analysis. RESULTS: In total, 58 patients (17 men and 41 women) were enrolled in this study. Among them, 30 knees were treated by MOS alone and 28 knees were treated by MOS with HTO. The MOCART scores of patients who received MOS alone were significantly lower in BME score (P = .0060), plug union score (P = .0216), and in plug necrosis score (P = .0326) than patients who received MOS with HTO. BME lesion was less likely to persist among elderly (odds ratio 1.20, P = .0248) and female (OR 41.8, P = .0118) patients. The MCID of Lysholm score was 6.6 in MOS alone and 8.4 in MOS with HTO cases, but there were no significant association between MRI findings and the postoperative Lysholm score. CONCLUSIONS: The MOS with HTO cases had better MOCART scores with less BME, better plug union, and less plug necrosis compared with MOS alone cases. Female and older patients had better resolution of BME, but there was no significant correlation between MRI findings and the postoperative Lysholm score. All cases in both groups showed improvement of Lysholm score exceeding MCID; thus, MOS may be effective as a joint preserving surgery for SIFK. LEVEL OF EVIDENCE: Level IV, clinical case series.

Patellar medial-lateral position can be used to correct the effect of leg rotation on preoperative planning in total knee arthroplasty for varus knees.

BACKGROUND: Lower limb malrotations can be observed in long leg radiographs, affecting the measurement of the angle between the mechanical and anatomical axes. The purposes were to analyze the effect of limb rotation and to evaluate the accuracy of the corrected angle between the mechanical and anatomical axes based on the patellar ML position. HYPOTHESIS: The hypothesis was that the correction of the angle between the mechanical and anatomical axes according to the patellar ML position can reduce the error from the angle in the true AP view in most of the knees. PATIENTS AND METHODS: A total of 100 consecutive knees with varus deformity undergoing primary total knee arthroplasty were included. Computed tomography images were digitally reconstructed in the neutral position, and internally and externally rotated at 10° and 20°, respectively. The patellar ML position relative to the medial (0%) and lateral (100%) epicondyles and the angle between the mechanical and anatomical axes of the femur were measured. The corrected angle between the mechanical and anatomical axes was calculated using the averaged translational ratio. RESULTS: In the neutral position, the patellar center position was 56.1% (standard deviation [SD]=4.7%), which was 31.4% (SD=7.2%) and 80.2% (SD=5.4%) in the 20° internal and external rotation, respectively. The angle between the mechanical and anatomical axes was 2.6° (SD=2.0°) and 8.1° (SD=2.1°) in the 20° internal and external rotation, respectively. On average, if the patellar center shifted 10%, the change of the angle between the mechanical and anatomical axes of the femur was 1.13°. Applying the corrected angle, a discrepancy from the neutral position decreased. CONCLUSION: The method to correct the angle between the mechanical and anatomical axes according to the patellar ML position can be used to reduce the measurement error for preoperative planning using a long leg radiograph. LEVEL OF EVIDENCE: III.

Opening-Wedge High Tibial Osteotomy With High Hinge Position Risks Lateral Hinge Fracture in Men With Posterolateral Tibial Condyle Protrusion.

PURPOSE: The primary aim of this study was to evaluate the 3-dimensional morphology of the proximal tibia around the osteotomy plane in open-wedge high tibial osteotomy, focusing on the posterolateral (PL) and posteromedial (PM) tibial condyles, and to clarify the changes in morphologic parameters due to differences in patient characteristics and hinge position. The secondary aim was to examine whether morphologic features were associated with insufficient osteotomy, which increases the risk of lateral hinge fracture (LHF). METHODS: The PL and PM anteroposterior distance, asymmetry ratio, and discrepancy between PL and PM distances along the tibial osteotomy plane were measured. We investigated changes in the parameters due to differences in patient characteristics and hinge position. Osteotomy configurations and LHFs were evaluated using postoperative computed tomography scans. RESULTS: The 3-dimensional preoperative plans of 117 knees (male, 41 knees; female, 76 knees) were evaluated. PL distances were larger than PM distances in almost all cases. The average asymmetry ratio was 1.35, and the standard deviation was 0.22. Higher hinge position was associated with a larger asymmetry ratio and discrepancy (P < .001). The asymmetry ratio and discrepancy were independently positively correlated with male sex (P = .002 and P = .001, respectively) and gentle posterior tibial slope (P < .001 and P < .001, respectively). Osteotomies with type III LHFs showed lower osteotomy sufficiency than osteotomies without LHFs (P < .001). CONCLUSIONS: PL tibial condyle protrusion was more pronounced in male patients and those with a high hinge position, and may result in insufficient PL osteotomy, which is a risk factor for type III LHF during open-wedge high tibial osteotomy. The optimal hinge position was located approximately 15 mm and 20 mm distal to the lateral tibial plateau in female and male patients, respectively. LEVEL OF EVIDENCE: IV: retrospective case series.

Bisphosphonate use is associated with a decreased joint narrowing rate in the non-arthritic hip.

AIMS: The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. METHODS: We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren-Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. RESULTS: A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = -0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). CONCLUSION: The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis.Cite this article: Bone Joint Res 2022;11(11):826-834.

Role of Lysine-Specific Demethylase 1 in Metabolically Integrating Osteoclast Differentiation and Inflammatory Bone Resorption Through Hypoxia-Inducible Factor 1α and E2F1.

OBJECTIVE: Hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis (RA). It alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. The mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. This study was undertaken to evaluate whether the protein lysine-specific demethylase 1 (LSD1) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis. METHODS: LSD1-specific inhibitors and gene silencing with small interfering RNAs were used to inhibit the expression of LSD1 in human osteoclast precursor cells derived from CD14-positive monocytes, with subsequent assessment by RNA-sequencing analysis. In experimental mouse models of arthritis, inflammatory osteolysis, or osteoporosis, features of accelerated bone loss and inflammatory osteolysis were analyzed. Furthermore, in blood samples from patients with RA, cis-acting expression quantitative trait loci (cis-eQTL) were analyzed for association with the expression of hypoxia-inducible factor 1α (HIF-1α), and associations between HIF-1α allelic variants and extent of bone erosion were evaluated. RESULTS: In human osteoclast precursor cells, RANKL induced the expression of LSD1 in a mechanistic target of rapamycin-dependent manner. Expression of LSD1 was higher in synovium from RA patients than in synovium from osteoarthritis patients. Inhibition of LSD1 in human osteoclast precursors suppressed osteoclast differentiation. Results of transcriptome analysis identified several LSD1-mediated hypoxia and cell-cycle pathways as key genetic pathways involved in human osteoclastogenesis. Furthermore, HIF-1α protein, which is rapidly degraded by the proteasome in a normoxic environment, was found to be expressed in RANKL-stimulated osteoclast precursor cells. Induction of LSD1 by RANKL stabilized the expression of HIF-1α protein, thereby promoting glycolysis, in conjunction with up-regulation of the transcription factor E2F1. Analyses of cis-eQTL revealed that higher HIF-1α expression was associated with increased bone erosion in patients with RA. Inhibition of LSD1 decreased pathologic bone resorption in mice, both in models of accelerated osteoporosis and models of arthritis and inflammatory osteolysis. CONCLUSION: LSD1 metabolically regulates osteoclastogenesis in an energy-demanding inflammatory environment. These findings provide potential new therapeutic strategies targeting osteoclasts in the management of inflammatory arthritis, including in patients with RA.

Pain catastrophizing hinders Disease Activity Score 28 - erythrocyte sedimentation rate remission of rheumatoid arthritis in patients with normal C-reactive protein levels.

AIM: This study aimed to assess the relationship between pain catastrophizing and achievement of 28-joint Disease Activity Score-defined remission of rheumatoid arthritis (RA), considering the presence or absence of systemic inflammation, and to evaluate associated factors for pain catastrophizing. METHOD: This cross-sectional study included 421 RA outpatients. The relationship between pain catastrophizing and remission was analyzed by adjusting several confounding factors. Univariable and multivariable analyses were performed to determine the relationship between pain catastrophizing and RA-related factors, comorbidities, and lifestyle habits. RESULTS: The prevalence of pain catastrophizing was 26%. Pain catastrophizing was negatively associated with remission (odds ratio 0.62, 95% confidence interval 0.38-1.00, P = .048). A multinomial logistic analysis showed that the presence of pain catastrophizing was an independent factor that was negatively correlated with the achievement of remission in the absence of systemic inflammation (odds ratio 0.51, 95% confidence interval 0.28-0.93, P = .029). Factors associated with elevated ratings on the Pain Catastrophizing Scale were a history of falls within the past year, a Health Assessment Questionnaire score >0.5, and smoking habit. Further, patients' subjective symptoms, including patient global assessment minus evaluator global assessment values ≥20 and high tender joint count minus swollen joint counts, were associated with elevated pain catastrophizing. CONCLUSION: Pain catastrophizing is a major obstacle to achieving remission in RA patients with normal C-reactive protein levels. Advanced physical disability, smoking habit, and history of falls were associated with pain catastrophizing, in addition to patients' subjective symptoms.