Human uncultured adipose-derived stromal vascular fraction shows therapeutic potential against osteoarthritis in immunodeficient rats via direct effects of transplanted M2 macrophages.

BACKGROUND: The uncultured adipose-derived stromal vascular fraction (SVF), consisting of adipose-derived stromal cells (ADSCs), M2 macrophages (M2Φ) and others, has shown therapeutic potential against osteoarthritis (OA), however, the mechanisms underlying its therapeutic effects remain unclear. Therefore, this study investigated the effects of the SVF on OA in a human-immunodeficient rat xenotransplantation model. METHODS: OA model was induced in the knees of female immunodeficient rats by destabilization of the medial meniscus. Immediately after the surgery, human SVF (1 × 105), ADSCs (1 × 104), or phosphate buffered saline as a control group were transplanted into the knees. At 4 and 8 weeks postoperatively, OA progression and synovitis were analyzed by macroscopic and histological analyses, and the expression of collagen II, SOX9, MMP-13, ADAMTS-5, F4/80, CD86 (M1), CD163 (M2), and human nuclear antigen (hNA) were evaluated immunohistochemically. In vitro, flow cytometry was performed to collect CD163-positive cells as M2Φ from the SVF. Chondrocyte pellets (1 × 105) were co-cultured with SVF (1 × 105), M2Φ (1 × 104), and ADSCs (1 × 104) or alone as a control group, and the pellet size was compared. TGF-ß, IL-10 and MMP-13 concentrations in the medium were evaluated using enzyme-linked immunosorbent assay. RESULTS: In comparison with the control and ADSC groups, the SVF group showed significantly slower OA progression and less synovitis with higher expression of collagen II and SOX9, lower expression of MMP-13 and ADAMTS-5, and lower F4/80 and M1/M2 ratio in the synovium. Only the SVF group showed partial expression of hNA-, CD163-, and F4/80-positive cells in the rat synovium. In vitro, the SVF, M2Φ, ADSC and control groups, in that order, showed larger pellet sizes, higher TGF-ß and IL-10, and lower MMP-13 concentrations. CONCLUSIONS: The M2Φ in the transplanted SVF directly affected recipient tissue, enhancing the secretion of growth factors and chondrocyte-protecting cytokines, and partially improving chondrocytes and joint homeostasis. These findings indicate that the SVF is as an effective option for regenerative therapy for OA, with mechanisms different from those of ADSCs.

Real-world study comparing the efficacy of Janus kinase inhibitors in patients with difficult-to-treat rheumatoid arthritis.

OBJECTIVE: This study aimed to analyze the clinical efficacy of JAK inhibitors in difficult-to-treat rheumatoid arthritis (D2TRA) and non-D2TRA patients and evaluate the factors influencing their efficacy using real-world data. METHOD: Here, 159 JAK inhibitor-treated patients with rheumatoid arthritis were categorized into D2TRA and non-D2TRA groups. Data including the Clinical Disease Activity Index (CDAI) at initiation and 6 months after drug administration, drug retention months, and reason for discontinuation due to toxic adverse events were collected. RESULTS: The retention rates at 6 months were 64.0% (D2TRA) and 78.4% (non-D2TRA) and were significantly different between the two groups (p = 0.030). The discontinuation rate owing to toxic adverse events significantly differed between the two groups (p = 0.030). The CDAI-low disease activity (LDA) rates differed significantly between the two groups (non-D2TRA, 62.3%; D2TRA, 34%; p < 0.001). CDAI-LDA achievement at 6 months after drug introduction was significantly associated with the number of times that biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs were previously used and the CDAI at baseline in all patients treated with JAK inhibitors. However, no predictive factors were identified for D2TRA patients treated with JAK inhibitors. CONCLUSION: Compared to non-D2TRA patients, D2TRA patients demonstrated significantly lower drug retention rates, CDAI-LDA achievement rates, and safety of JAK inhibitors. No significant predictive factor for CDAI-LDA achievement 6 months after drug introduction was detected in D2TRA patients. Key Points • The retention of JAK inhibitors were significantly lower for the treatment of D2TRA patients in comparison with non-D2TRA patients. • The efficacy and safety of JAK inhibitors were significantly lower for the treatment of D2TRA patients. • Number of previous uses of b/tsDMARDs and CDAI at baseline were identified as the predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. • No significant predictive factor for CDAI-LDA achievement 6 months after drug introduction was detected in D2TRA patients.

Work productivity after periacetabular osteotomy was affected by preoperative progression of osteoarthritis and heavy workload.

INTRODUCTION: Many patients who have undergone a periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH) have had jobs preoperatively. Postoperative return to work and work productivity are important for livelihood security and the social economy. However, there is a lack of evidence on work productivity after PAOs. Therefore, this study investigated the return to work rates and influence of workload, clinical, and radiographic parameters on work productivity after a curved PAO. MATERIALS AND METHODS: In this study, the data of 68 hip joints among 48 participants who underwent curved PAO for symptomatic DDH were analyzed. Correlations between postoperative work productivity and clinical, radiographic, and workload parameters were assessed. Work productivity was evaluated using the Work Productivity and Activity Impairment (WPAI) questionnaire. Clinical factors were assessed using the modified Harris Hip Scores (mHHS) and University of California, Los Angeles Activity scores. Preoperative and postoperative radiographic parameters were compared with postoperative work productivity. The workload was categorized using the Reichsausschuß für Arbeitszeitermittlung (REFA)-classification system. RESULTS: Of the participants, 98% returned to work and 87.5% returned to their original jobs. Work productivity was significantly improved in all workload categories at the 1-year postoperative follow-up. Multivariate analysis demonstrated that preoperative Tönnis and REFA classification grades were significantly associated with the postoperative WPAI. CONCLUSION: Curved PAOs can improve postoperative work productivity and return to work rates. Preoperative progression of osteoarthritis and heavy workload affect postoperative work productivity.

Comparison of short-term clinical results between modified kinematically-aligned and guided motion bicruciate stabilized total knee arthroplasty.

BACKGROUND: Both kinematically-aligned (KA) total knee arthroplasty (TKA) and bicruciate stabilized (BCS) TKA aim to reproduce the physiological knee kinematics. In this study, we compared the femoro-tibial component rotational mismatch between patients who underwent modified KA-TKA and those who received guided-motion BCS-TKA, and its influence on the clinical outcomes. METHODS: In this retrospective study, 77 consecutive patients were included and divided into two groups: subjects who underwent modified KA-TKA with Persona (KA Group; n = 42) and those who received BCS-TKA with JOURNEY II (BCS group; n = 35). Range of motion, the 2011 Knee Society Score (KSS), the rotational alignment of the femoral and tibial components, and the correlations between the rotational mismatch and the 2011 KSS subscales were examined. RESULTS: The postoperative objective knee indicators (P = 0.0157), patient satisfaction (P = 0.0039) and functional activity scores (P = 0.0013) in the KA group were significantly superior to those in the BCS group 1 year postoperatively. There was no significant difference between the two groups observed in the rotational mismatch. In the BCS group, significant negative correlations were identified between the rotational mismatch and objective indicators, patient satisfaction, and functional activity scores but not in the KA group. CONCLUSIONS: The short-term clinical results following KA-TKA showed superior objective knee indicators, patient satisfaction and functional activity scores. A negative correlation was observed between component rotational mismatch and the 2011 KSS subscales in the BCS group, compared to no relationship found between the two in the KA group. These findings suggested that KA-TKA has a relatively higher tolerance for rotational mismatch than BCS-TKA.

Intraoperative lateral laxity greater than 4° is associated with inferior functional improvement in posterior-stabilised total knee arthroplasty.

PURPOSE: The study aimed to determine the impact of intraoperative lateral laxity at extension on clinical and functional outcomes 1 year after posterior-stabilised total knee arthroplasty (PS-TKA). METHODS: In total, 91 varus-type osteoarthritic knees that underwent PS-TKA using the medial preservation gap technique were included. After the femoral trial component placement and patellofemoral joint reduction, the soft-tissue balance was assessed using an offset-type tensor with a 40-lb joint-distraction force. Patients were divided into the following three groups according to the intraoperative lateral laxity at extension (i.e., varus ligament balance) using the mean ± 1 standard deviation: Groups A, ≤0°; B, 0-4°; and C, >4°. The 2011 Knee Society Score (KSS) and 3-m timed up-and-go test (TUG) time 1-year postoperatively, and their improvements were compared among the groups. RESULTS: While significant improvements were observed in all subscales of the 2011 KSS and TUG post-TKA (p < 0.05), the improvement of functional activities and TUG time were significantly lower in Group C than in Group B (p < 0.05). However, no significant differences were observed in symptom improvement, patient satisfaction or patient expectation scores among the groups. CONCLUSION: An excessive lateral laxity (varus angle) >4° at extension was associated with lower improvement in functional ability 1-year postoperatively. Therefore, excessive intraoperative lateral laxity should be avoided in PS-TKA. LEVEL OF EVIDENCE: Level IV.

Combined assessment of acetabular coverage and femoral head-neck shapes predicts osteoarthritis progression after periacetabular osteotomy.

INTRODUCTION: Postoperative osteoarthritis (OA) progression is a major determinant of failure after curved periacetabular osteotomy (CPO). A large postoperative combination angle, i.e., the combination of computed tomography-based anterior center edge and alpha angles, is associated with femoroacetabular impingement after CPO, but its association with postoperative OA progression is unclear. We aimed to identify the anatomical parameters that can lead to OA progression after CPO and the impact of the combination angle on the same. MATERIALS AND METHODS: We included 90 hips that were subjected to CPO at our center between March 2013 and March 2018. Seventeen hips showed OA progression with an increase in the Tönnis classification after surgery; 73 hips showed no progression. Radiographic anatomical parameters, including the lateral and anterior center edge angles, femoral and acetabular anteversion, and combination angle, and clinical outcomes, including modified Harris Hip Scores (mHHSs), postoperative anterior impingement, and range of motion, were compared between the two groups. Statistical significance was set at P < 0.05. RESULTS: Postoperative OA progression was significantly affected by preoperative OA evidence (P = 0.017), acetabular anteversion < 5.0° (P = 0.003), and a combination angle > 107.0° (P = 0.025). Patients with radiographic OA progression were associated with poor mHHSs (P = 0.017) and high frequencies of anterior impingement with a limited hip flexion and internal rotation angle. CONCLUSIONS: OA progression after CPO may be associated with preoperative evidence of OA and postoperative acetabular retroversion as well as a large combination angle. Surgeons should focus on the potential effects of preoperative OA grades, postoperative reduction in acetabular anteversion, and postoperative combination angle.

The assessment of canal flare index and proximal femoral bone density can improve stem selection for peri-prosthetic bone maintenance after total hip arthroplasty.

INTRODUCTION: Bone maintenance after total hip arthroplasty (THA) is important for implant success. This study aimed to investigate the relationship between patient characteristics and periprosthetic bone maintenance after THA for better implant selection. MATERIALS AND METHODS: This retrospective cohort study enrolled 112 consecutive patients who underwent THA using full hydroxyapatite (HA) compaction with short (n = 55) or short-tapered wedge (n = 61) stems. Periprosthetic bone mineral density (BMD) was compared between the two groups after propensity score matching, and the relationship between periprosthetic BMD changes and patient background was analyzed. RESULTS: Both groups showed similar periprosthetic BMD changes after adjusting for patient background using propensity score matching. Canal flare index > 3.7 in patients that underwent THA using tapered-wedge stem (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3-7.9, p = 0.013) and baseline zone 1 BMD > 0.65 in patients that received with short HA compaction stems (OR, 430.0; 95% CI 1.3-1420, p = 0.040) were associated with proximal periprosthetic bone maintenance after THA. CONCLUSION: Considering their predictive value, canal flare index and zone 1 BMD assessment might be useful strategies for implant selection during THA.

Accuracy of portable navigation during THA in patients with severe developmental dysplasia of hip.

INTRODUCTION: Correct cup placement in total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH) is considerably difficult. This study aimed to analyze the orientation accuracy of cup insertion during THA using a portable navigation system in patients with DDH. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed data from 64 patients who underwent THA using infrared stereo camera-matching portable navigation. Patients underwent THA via the anterolateral approach in the lateral decubitus position. Navigation records for intraoperative cup angles, postoperative cup angles measured on computed tomography (CT) images, and cup angle measurement differences were measured and compared between patients with non-DDH/mild DDH and severe DDH. Furthermore, the predictive factors for outliers of accurate acetabular cup placement were analyzed. RESULTS: The average measurement absolute abduction differences (postoperative CT-navigation record) were 3.9 ± 3.5° (severe DDH) and 3.3 ± 2.6° (non-DDH/ mild DDH), and the anteversion differences were 4.7 ± 3.4° (severe DDH) and 2.3 ± 2.1° (non-DDH/ mild DDH). The anteversion difference was different between the two groups. Multivariate analysis showed that the navigation difference (absolute difference in anteversion between postoperative CT and navigation records of > 5°) was significantly associated with severe DDH (odds ratio [OR]: 3.3; p = 0.049, 95% confidence interval [CI]: 1.0-11.1) and posterior pelvic tilt (OR: 1.1; p = 0.042, 95% CI: 1.0-1.27). CONCLUSIONS: In patients with severe DDH, it is important to pay close attention during THA using portable navigation. However, the average difference was < 5º even in patients with severe DDH, and the accuracy may be acceptable in a clinical setting when the cost is considered.

What effect does preoperative flexion contracture have on the component angles in unicompartmental knee arthroplasty?

PURPOSE: The indication for unicompartmental knee arthroplasty (UKA) has been extended to cases with some degree of preoperative knee flexion contracture recently. The purpose of this study was to clarify the effect of flexion contracture on component angles. MATERIALS AND METHODS: Thirty-five fixed-bearing UKAs using the spacer block technique with preoperative flexion contracture (Group FC) and 35 UKAs using the same technique without preoperative flexion contracture (Group NC) were included. Using radiographs, the coronal femoral component angle, coronal tibial component angle, sagittal femoral component angle, and sagittal tibial component angle were determined. Also, extension and flexion angles of the knee as well as coronal Hip-Knee-Ankle (HKA) angles in long-leg standing radiographs were measured. The data about the thickness of the selected insert were also collected. The above results were compared between the two groups. RESULTS: The femoral component tended to be placed in a more varus and flexed position in Group FC, while no significant difference was found about the tibial component angles. While there was no significant difference in pre- and postoperative knee flexion angles between the two groups, flexion contracture remained postoperatively in Group FC. Preoperative HKA angle was greater in Group FC while the difference was no longer significant postoperatively. Regarding the thickness of the selected insert, thicker inserts tended to be used in Group FC. CONCLUSIONS: In fixed-bearing UKA with the spacer block technique, the femoral component tended to be placed in a flexed and varus position in the knees with preoperative flexion contracture.

Prediction of 3-Dimensional Coverage Surface Area of the Femoral Head in Hip Dysplasia Through Conventional Computed Tomography.

Background: Assessment of 3-dimensional (3D) femoral head coverage is critical in evaluating, preoperative planning, and treating hip dysplasia. Purpose: To (1) propose a mathematical model to establish 3D femoral head coverage using conventional computed tomography (CT), (2) determine the correlation of 2D parameters with 3D coverage, and (3) characterize the patterns of dysplasia based on 3D morphology. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We identified 30 patients (n = hips) with symptomatic dysplasia and 30 patients (n = hips) without dysplasia. Patients with dysplastic hips were matched with regard to sex, age, and body mass index to those with nondysplastic hips. Preoperative CTs were analyzed using 3D software, and 3D femoral head surface area coverage (FHSAC; in %) was assessed in 4 quadrant zones: anteromedial, anterolateral, posteromedial, and posterolateral. To assess lateral coverage of the femoral head, we introduced the anterolateral femoral head coverage angle (ALFC) and the posterolateral femoral head coverage angle (PLFC). Results: Reduced femoral head coverage was more pronounced in dysplastic versus nondysplastic hips in the anterolateral quadrant (18% vs 40.7%, respectively) and posterolateral quadrant (35.8% vs 56.9%, respectively) (P < .0001 for both). Dysplastic hips had smaller ALFC and PLFC (18.4° vs 38.7°; P < .0001; 47.2° vs 72.3°; P = .0002). Anterolateral and posterolateral FHSAC were strongly correlated with the ALFC (r = 0.88; P < .0001) and the PLFC (r = 0.82; P < .0001) along with the lateral center-edge angle (anterolateral, r = 0.75; P < .0001; posterolateral, r = 0.73; P < .0001). Prediction models established for FHSAC had strong agreement with explanatory CT variables (anterolateral: r = 0.91; P < .0001; posterolateral: r = 0.90; P < .0001). The cutoff values for anterolateral and posterolateral FHSAC were 25% and 41%, respectively. In dysplastic hips, global deficiency was most common (15/30 hips), 9 hips showed an anterolateral deficiency, and 4 hips had a posterolateral deficiency pattern. Conclusion: The ALFC and The PLFC were strongly correlated with 3D lateral FHSAC and were able to predict 3D coverage accurately.

Mid- to Long-Term Results of Total Knee Arthroplasty for Charcot Arthropathy of the Knee.

Background: Total knee arthroplasty (TKA) for Charcot arthropathy of the knee is considered controversial because of its higher complication rate compared with that of TKA for osteoarthritis. In this study, we investigated the clinical outcomes, survival rates, and complications of primary TKA for Charcot arthropathy. Methods: We conducted a retrospective analysis of nine patients (12 knees) with Charcot arthropathy who underwent TKA. The mean age of the patients was 63.9 ± 9.4 years (range, 52-83 years). The most frequent causative disease was diabetes mellitus (three patients). Patients' clinical outcomes, including the 2011 Knee Society Score and the range of motion, were compared between preoperative and the most recent postoperative data. The 5- and 10-year survival rates for aseptic revision, revision due to infection, and complications were examined. The mean follow-up period was 7.3 ± 3.9 years (range, 3-14 years). Results: The 2011 Knee Society Score and the knee flexion angle significantly improved after TKA surgery (P < 0.05). The 5-year survival rates for aseptic revision, revision due to infection, and complications were 100%, 91.7%, and 83.3%, respectively; the 10-year survival rates for these parameters were the same. One patient underwent revision for insert replacement due to periprosthetic infection, and the other patient had varus/valgus instability due to soft tissue loosening. Conclusions: The mid- to long-term results of TKA for Charcot arthropathy were generally favorable. Our findings indicate that TKA may be a viable treatment option for Charcot arthropathy.

Varus placement of the tibial component reduces the potential risk of fracture with adequate bony coverage in the Oxford unicompartmental knee arthroplasty.

A short keel-cortex distance (KCD), especially to the posterior cortex, is a potential risk factor for tibial plateau fracture after Oxford mobile-bearing unicompartmental knee arthroplasty (OUKA). This study aimed to evaluate the effect of tibial component alignment in the coronal plane and tibial proximal morphology on the KCD. Included in this study were 51 patients scheduled for primary Oxford medial unicompartmental knee arthroplasty (UKA). The anterior and posterior KCD were preoperatively assessed using 3D simulation software with the component set perpendicular to the tibial mechanical axis (neutral), 3° valgus, 3° varus, and 6° varus, relative to neutral alignment. We evaluated the existence of overhanging medial tibial condyle where the medial eminence line, the line including the medial tibial eminence parallel to the tibial axis, passes outside of the tibial shaft. In all component alignments, patients with a medial overhanging condyle had significantly shorter posterior KCD than those without. In patients with a medial overhanging condyle, the posterior KCD significantly increased when the tibial component was placed in 3° varus (4.6 ± 1.5 mm, P = 0.003 vs neutral, P < 0.001 vs 3° valgus) and 6° varus (5.0 ± 1.4 mm, P < 0.001 vs neutral, P < 0.001 vs 3° valgus) compared with in neutral (3.5 ± 1.9 mm) or 3° valgus (2.8 ± 1.8 mm). In OUKA, varus implantation increased the KCD. This could potentially decrease the risk of fracture, even in knees with the overhanging medial condyle. Conversely, valgus implantation of the tibial component shortened the KCD, and should therefore be avoided.

Influence of Distal Reference Point of the Tibial Mechanical Axis on the Ankle and Hindlimb Alignment Change after Total Knee Arthroplasty.

The alignment philosophy in total knee arthroplasty (TKA) has tended to shift from the gold standard of mechanically aligned technique to personalized alignment, such as the kinematically aligned (KA) technique. However, the influences of different surgical techniques on lower limb alignment relative to the ground are not fully investigated. This study investigated the influence of the ankle and hindlimb alignment change after mechanically aligned TKA and KA-TKA. The varus osteoarthritic patients who underwent TKAs were divided into a mechanically aligned TKA group (group M, n = 50) and a KA-TKA group (group K, n = 50). Radiographic parameters (hip-knee-calcaneus [HKC] angle, hip-knee-ankle [HKA] angle, talar tilt angle [TTA], and tibiocalcaneal angle [TCA]) were investigated using full-length standing radiographs. The deviation angle (ΔTA; angle between the tibial mechanical axis [TMA] and the ground tibial mechanical axis [gTMA]) and the change of ΔTA (cΔTA) were also assessed. These parameters were compared between the two groups, along with the correlation between the preoperative HKA angle and other parameters. ΔTA, TTA, and TCA showed no differences between the groups pre- and postoperatively, and no significant changes were observed postoperatively. The preoperative HKA angle showed a significant negative correlation with cΔTA in both groups (group M: r = -0.33, p = 0.02; group K: r = -0.29, p = 0.04) although no correlation was observed the with preoperative TTA and TCA. Despite no change in ΔTA after surgery, the preoperative varus deformity was associated with a change in the deviation between gTMA and TMA after surgery. A severely varus knee may be inappropriate for ground KA-TKA.

Predicting postoperative coronal alignment after fixed-bearing unicompartmental knee arthroplasty using a new morphological assessment method: the arithmetic hip-knee-ankle angle.

PURPOSE: Only a few reports have been published so far on factors that predict postoperative coronal alignment after unicompartmental knee arthroplasty (UKA). The purpose of this study is to clarify the relationship between the arithmetic hip-knee-ankle angle (aHKA) and postoperative coronal alignment after medial fixed-bearing UKA. METHODS: One hundred and one consecutive patients (125 knees) who underwent medial fixed-bearing UKA were assessed. Pre- and postoperative coronal HKA angles, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and the thickness of the tibial and femoral bone cut were measured. aHKA was calculated as 180° - LDFA + MPTA. Correlations between postoperative HKA angle and aHKA, LDFA, and MPTA were investigated by single regression analysis. After the patients were divided into three groups according to the postoperative HKA angle, i.e., HKA angle > 180°, 175° < HKA angle ≤ 180°, and HKA angle ≤ 175°, aHKA, LDFA, MPTA, preoperative HKA angle, and the thickness of the distal femoral as well as tibial bone cut were compared among the three groups. RESULTS: aHKA and MPTA were positively correlated with postoperative HKA angle, while no correlation was found between postoperative HKA angle and LDFA. Among the three groups classified by postoperative HKA angle, significant differences were found in aHKA, MPTA, and preoperative HKA angle, while no significant difference was found in LDFA and the amount of distal femoral and tibial osteotomies. CONCLUSIONS: aHKA was correlated with postoperative HKA angle after medial fixed-bearing UKA, which was probably due to the influence of MPTA.

Successful Total Knee Arthroplasty for Hoffa and Proximal Tibial Fractures: Report of Three Complex Cases After Failed Osteosynthesis Procedures.

BACKGROUND Distal femoral and proximal tibial fractures often lead to nonunion and post-traumatic osteoarthritis, and total knee arthroplasty (TKA) has emerged as an effective alternative for older patients. This report includes 3 cases of successful TKA treatment. The cases involve a 42-year-old man and a 62-year-old man with Hoffa coronal fractures of the distal femur, and a 50-year-old man with a proximal tibial fracture. These patients underwent multiple osteosynthesis procedures before receiving TKA. CASE REPORT Case 1: A 42-year-old man with a displaced Hoffa's fracture had persistent knee pain. Nonunion post-initial fixation led to reoperation with iliac bone grafting and plate fixation. TKA using a Posterior Stabilized (PS)-type implant resulted in improved motion and function after 3 years. Case 2: A 62-year-old man suffered lateral condyle and ligament injuries from a displaced Hoffa's fracture. Despite plate fixation, dislocation occurred, requiring conversion. TKA with long-stem hinge-type implant, using augmentation block, led to enhanced stability and outcomes at 2 years. Case 3: A 50-year-old man's tibial nonunion, treated with plate fixation, resulted in infection and bone fusion. TKA using a constrained PS-type implant insert addressed the lateral tibial adhesions via iliotibial band (ITB) release and treated severe tibial plateau damage. Positive results were seen at 1 year. CONCLUSIONS The challenges of pseudarthrosis, like bone defects and compromised tissue, highlight the need for precise implant selection based on evaluations of bone quality, defects, knee stability, and hyperextension, rather than resorting to overly-constrained implants.

Revealing a Natural Model of Pre-Osteoarthritis of the Hip Through Study of Femoroacetabular Impingement.

Femoroacetabular impingement (FAI) is considered the mechanical cause of hip osteoarthritis (OA). Surgical intervention involves labrum repair and osteochondroplasty to remove the impingement, alleviating symptoms. Nevertheless, some patients progress to hip OA after surgery, indicating that factors other than mechanical abnormality are contributing to hip OA progression. This review article discusses our laboratory's studies on hip FAI and OA, undertaken to identify key molecular players in the progression of hip OA. Transcriptome analysis identified peroxisome proliferator activated receptor gamma (PPARγ) as a crucial molecule in early hip OA. PPARγ, widely expressed in chondrocytes, has a protective role in preventing OA, but its true mechanism remains unknown. We observed a dysregulation of DNA methyltransferase (DNMT) in the progression of hip OA, with high expression of DNMT1 and 3A and downregulation of DNMT3B. Moreover, we established that DNMT3A is the main molecule that is binding to PPARγ promoter CpG area, and hypermethylation of this area occurs during disease progression. This suggests that epigenetic changes are a main mechanism that regulates PPARγ expression. Finally, we developed a novel rabbit model of hip FAI and OA and are currently performing studies to validate our small-animal model to human FAI.

Heterogeneous Cells as well as Adipose-Derived Stromal Cells in Stromal Vascular Fraction Contribute to Enhance Anabolic and Inhibit Catabolic Factors in Osteoarthritis.

The stromal-vascular fraction (SVF), comprising heterogeneous cell populations and adipose-derived stromal cells (ADSCs), has therapeutic potential against osteoarthritis (OA); however, the underlying mechanism remains elusive. This study aimed to investigate the therapeutic effects of heterogeneous cells in rabbit SVF on rabbit chondrocytes. Rabbit SVF and ADSCs were autografted into knees at OA onset. The SVF (1 × 105) and low-dose ADSCs (lADSC; 1 × 104) groups adjusted for their stromal cell content were compared. Animals were euthanized 8 and 12 weeks after OA onset for macroscopic and histological analyses of OA progression and synovitis. Immunohistochemical and real-time polymerase chain reaction assessments were conducted. In vitro, immune-fluorescent double staining was performed for SVF to stain macrophages with F4/80, CD86(M1), and CD163(M2). OA progression was markedly suppressed, and synovitis was reduced in the SVF groups (OARSI histological score 8 W: 6.8 ± 0.75 vs. 3.8 ± 0.75, p = 0.001; 12 W: 8.8 ± 0.4 vs. 5.4 ± 0.49, p = 0.0002). The SVF groups had higher expression of collagen II and SOX9 in cartilage and TGF-ß and IL-10 in the synovium, lower expression of MMP-13, and lower macrophage M1/M2 ratio than the lADSC groups. Immunofluorescent double staining revealed a markedly higher number of M2 than that of M1 macrophages in the SVF. The therapeutic effects of SVF on chondrocytes were superior than those of lADSCs, with enhanced anabolic and inhibited catabolic factors. Heterogeneous cells, mainly M2 macrophages in the SVF, enhanced growth factor secretion and chondrocyte-protective cytokines, thus benefiting chondrocytes and knee joint homeostasis. Overall, the SVF is a safe, relatively simple, and a useful treatment option for OA.

Mobile bearing orbit on the tibial component in Oxford unicompartmental knee arthroplasty.

PURPOSE: To evaluate the bearing orbit of the tibial component during extension-flexion motion in Oxford unicompartmental knee arthroplasty. MATERIALS AND METHODS: A total of 32 knees in 25 patients with medial osteoarthritis who underwent Oxford unicompartmental knee arthroplasty were evaluated. The distance between the vertical wall of the tibial component and the bearing (wall-bearing distance) and that between the anterior edge of the tibial component and the bearing (sagittal bearing position) were measured at 0°, 30°, 60°, 90° and 120° knee flexion with neutral tibial rotation (extension-flexion motion), and internal and external tibial rotation with 90° knee flexion (tibial rotation motion). A custom-made rounded trial bearing and caliper were used for this measurement. We calculated the wall-bearing distance, change in extension-flexion motion and tibial rotation motion. Wall-bearing distances and change in wall-bearing distance were compared using ANOVA or t-test. RESULTS: The wall-bearing distance was smallest at 60° and increased 1.0 ± 1.1 mm in knee extension and 1.1 ± 1.5 mm in knee flexion. The bearing moved posteriorly with knee flexion, and the sagittal bearing position increased by 8.1 ± 3.4 mm during extension-flexion motion. Consequently, the bearing moved in a rough C-shaped orbit of the tibial component. CONCLUSIONS: The mobile bearing moves in a rough C-shape and is mostly close to the vertical wall of the tibial component at 60°. The wall-bearing distance can change during extension-flexion motion and might be influenced by tibial component rotation. To avoid bearing separation from or contact with the vertical wall that may cause bearing dislocation, the wall-bearing distance should be evaluated before keel slot preparation.

Bearings can dislocate with smaller femoral components and thicker bearings in Oxford™ medial unicompartmental knee arthroplasty.

BACKGROUND: A mobile bearing can dislocate when joint laxity is larger than jumping height, the height difference between the bottom and the peak of the bearing (the highest point of the upper bearing surface on each side). Significant laxity due to improper gap balancing should therefore be avoided. However, once the bearing rotates vertically on the tibial component, the bearing can dislocate with smaller laxity than the jumping height. We mathematically calculated the required laxity for dislocation (RLD) and the required rotation of the bearing for dislocation (RRD). The current study addressed the question: 1) could the femoral component size and the bearing thickness affect the RLD and RRD? HYPOTHESIS: The femoral component size and the bearing thickness could affect the MLD and MRD. METHODS: The RLD and RRD were calculated using the bearing dimensions provided by the manufacturer with femoral component size, bearing thickness, and directions (anterior, posterior, and medial/lateral) as the variables on a two-dimensional basis. RESULTS: The RLD was 3.4 to 5.5mm in the anterior, 2.3 to 3.8mm in the posterior, and 1.4 to 2.4mm in the medial or lateral directions. The RLD decreased with a smaller femoral size or a thicker bearing. Similarly, the RRD decreased with a smaller femoral size or a thicker bearing thickness in all directions. CONCLUSIONS: Increased bearing thickness and decreased femoral component size deceased the RLD and RRD, which would relate to an increased risk of dislocation. Selecting the femoral component as large as possible and the bearing as thin as possible would therefore be helpful in the prevention of dislocation. LEVEL OF EVIDENCE: III; comparative computer simulation study.

Epigenetic dysregulation of articular cartilage during progression of hip femoroacetabular impingement disease.

Femoroacetabular impingement (FAI) is an important trigger of hip osteoarthritis (OA). Epigenetic changes in DNA methyltransferase 3B (DNMT3B) attenuate catabolic gene expression in cartilage hemostasis. This study aimed to examine the articular chondrocyte catabolic state and DNMT3B and 4-aminobutyrate aminotransferase promoter (ABAT) expression during OA progression in FAI. Cartilage samples were collected from the impingement zone of 12 patients with cam FAI (early-FAI) and 12 patients with advanced OA secondary to cam FAI (late-FAI-OA). Five healthy samples were procured from cadavers (ND: nondiseased). Explants were cultured under unstimulated conditions, catabolic stimulus (IL1ß), or anabolic stimulus (TGFß). Histology was performed with safranin-O/fast-green staining. Gene expression was analyzed via qPCR for GAPDH, DNMT3B, ABAT, MMP-13, COL10A1. Methylation specific PCR assessed methylation status at the ABAT promoter. Cartilage samples in early-FAI and late-FAI-OA showed a histological OA phenotype and increased catabolic marker expression (MMP13/COL10A1, ND vs. early-FAI, p = 0.004/p < 0.001, ND vs. late-FAI-OA, p < 0.001/p < 0.001). RT-PCR confirmed DNMT3B underexpression (ND vs. early-FAI, p < 0.001, early-FAI vs. late-FAI-OA, p = 0.016) and ABAT overexpression (ND vs. early-FAI, p < 0.001, early vs. late-FAI-OA, p = 0.035) with advanced disease. End-stage disease showed ABAT promoter hypomethylation. IL1ß stimulus accentuated ABAT promoter hypomethylation and led to further ABAT and catabolic marker overexpression in early-FAI and late-FAI-OA while TGFß normalized these alterations in gene expression. Catabolic and epigenetic molecule expression suggested less catabolism in early-stage disease. Sustained inflammation induced ABAT promoter hypo-methylation causing a catabolic phenotype. Suppression of ABAT by methylation control could be a new target for therapeutic intervention to prevent OA progression in hip FAI.