Morphological analysis of the distal femur as a surgical reference in biplane distal femoral osteotomy.

Distal femoral osteotomy (DFO) is performed alone or with high tibial osteotomy (HTO) for patients with osteoarthritis and distal femur deformities. DFO is technically demanding, particularly when creating an anterior flange. Herein, we examined the morphological characteristics of the distal femur based on the cortical shape as a surgical reference for biplanar DFO. Computed tomography images of 50 valgus and 50 varus knees of patients who underwent biplanar DFO or total knee arthroplasty were analyzed. Axial slices at the initial level of the transverse osteotomy in the DFO and slices 10 mm proximal and 10 mm distal to that level were selected. The medial and lateral cortical angles and heights (MCLA, LCLA, MCH, and LCH) were measured on axial slices. Statistical comparisons were performed between the medial and lateral cortices and valgus and varus knees. MCLA and MCH were significantly smaller and lower, respectively, than LCLA and LCH (P < 0.01). The MCLA and MCH of varus knees were significantly smaller and lower, respectively, than those of valgus knees (P < 0.01). Surgeons should carefully observe morphological differences in the distal femur cortex, distinguishing between medial and lateral knees and varus and valgus knees during the creation of the anterior flange in the DFO.

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.

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.

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.

Association Between Psychological Readiness to Return to Sports at 3 Months Postoperatively and Risk of Second ACL Injury.

Background: Psychological readiness to return to sports (RTS) has been associated with second anterior cruciate ligament (ACL) injury. However, this relationship is controversial because covariates such as anatomic and knee function characteristics have not been adequately considered. Purpose/Hypothesis: To investigate whether psychological readiness in the early postoperative period can predict the occurrence of a second ACL injury within 24 months after primary ACL reconstruction (ACLR) using propensity score analysis. It was hypothesized that patients with high ACL-RSI after injury (ACL-RSI) scores at 3 months postoperatively would have a second ACL injury within the projected postoperative period. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 169 patients who underwent primary ACLR using hamstring tendon autografts between November 2017 and July 2021 and also underwent knee functional assessments at 3 months postoperatively. The ACL-RSI scale was used to assess psychological readiness for RTS. A second ACL injury was defined if ipsilateral or contralateral ACL injury was confirmed by examination within 24 months postoperatively. Based on a previous study showing that 65 was the highest cutoff value for the ACL-RSI score for RTS, we classified patients into 2 groups: those with high ACL-RSI scores (≥65; group H) and those with low ACL-RSI scores (<65; group L). We generated 1-to-1 matched pairs using propensity score analysis and used log-rank testing to compare the rate of second ACL injury between the 2 groups. Results: More patients returned to any sports activities within 12 months in group H than in group L (90% vs 73%; P = .03). A second ACL injury within 24 months postoperatively was identified in 7% of patients (13/169). The rate of second ACL injury was significantly higher in group H than in group L (17.6% vs 3.4%; P = .001). In 43 matched pairs extracted using propensity scoring, the rate of second ACL injury was also higher in group H than in group L (18.6% vs 4.7%; P = .04). Conclusion: Patients with a higher ACL-RSI score at 3 months exhibited a significantly higher incidence of second ACL injury within 24 months after primary ACLR.

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.

Prediction of Postoperative Range of Motion after Mobile-Bearing Medial Unicompartmental Knee Arthroplasty from the Preoperative Range of Motion and Other Preoperative Factors.

Postoperative flexion after unicompartmental knee arthroplasty might be predicted from the preoperative range of motion and other preoperative factors, but this has not been sufficiently investigated. Between 2013 and 2017, 198 patients (198 knees) underwent unilateral knee arthroplasty with medial mobile-bearing unicompartmental knee arthroplasty. Range of motion was measured preoperatively and at the time of final follow-up. To investigate the accuracy of the prediction of preoperative to postoperative gain or loss of the flexion angle, we performed receiver operating characteristic analysis. Logistic regression analysis was used to evaluate other predictive factors. Change in flexion angle was significantly strongly and negatively correlated with the preoperative flexion angle (R = - 0.688; 95% confidence interval: -0.755 to -0.607; p < 0.001). Preoperative flexion angle was suggested to be a significant predictor of gain or loss of the flexion angle with the area under the curve of 0.781; the cutoff value calculated using the Youden index was 140 degrees. Logistic regression analysis showed that in addition to the preoperative flexion angle of the operated side, the postoperative flexion range was significantly affected by the patient's height and by the preoperative flexion angle of the contralateral knee. If the preoperative flexion angle in Oxford mobile-bearing medial unicompartmental knee arthroplasty is <140 degrees, the postoperative flexion angle may be improved; if it exceeds 140 degrees, the postoperative flexion angle may worsen. This predictive ability is further improved by consideration of the patient's height and the range of motion on the contralateral side.

LIGHT regulated gene expression in rheumatoid synovial fibroblasts.

BACKGROUND: Synovial hyperplasia caused by rheumatoid arthritis (RA), an autoimmune inflammatory disease, leads to the destruction of the articular cartilage and bone. A member of the tumor necrosis factor superfamily, Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) has been shown to correlate with the pathogenesis of RA. METHODS: We used cDNA microarray analysis to compare the expression of genes in rheumatoid fibroblast-like synoviocytes with and without LIGHT stimulation. RESULTS: Significant changes in gene expression (P-values < 0.05 and fold change ≥ 2.0) were associated mainly with biological function categories of glycoprotein, glycosylation site as N-linked, plasma membrane part, integral to plasma membrane, intrinsic to plasma membrane, signal, plasma membrane, signal peptide, alternative splicing, and topological domain as extracellular. CONCLUSIONS: Our results indicate that LIGHT may regulate the expression in RA-FLS of genes which are important in the differentiation of several cell types and in cellular functions.

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.

Knee Osteotomy Decreases Joint Inflammation Based on Synovial Histology and Synovial Fluid Analysis.

PURPOSE: To examine the biological changes in the joints of patients with knee osteoarthritis (OA) before and after around-knee osteotomy (AKO), focusing on synovial fluid (SF) and synovial pathological changes. METHODS: Patients who underwent AKO for medial compartment knee OA between 2019 and 2021 were examined. SF and synovium were obtained at the time of AKO and plate removal after bone union (mean, 16.8 months [range: 11-38 months] postoperatively). SF volume and interleukin (IL)-6 concentrations in SF were assayed using enzyme-linked immunosorbent assay. Synovitis was assessed histologically using a semiquantitative scoring system. Macrophage infiltration was assessed by immunohistochemistry using a semiquantitative score for F4/80 expression. The M1/M2 ratio was calculated using percentage of cells positive for CD80 and CD163. The expression of proinflammatory cytokines was assessed by the percentage of IL-1ß- and IL-6-positive cells. The number of vascular endothelial growth factor-positive luminal structures was counted to assess angiogenesis. The change in each parameter was compared before and after AKO using the Wilcoxon matched-pairs signed-rank test. RESULTS: Twenty-four knees of 21 patients were included. SF volume and IL-6 concentration significantly decreased postoperatively (12.6 ± 2.1 mL vs 4.2 ± 0.6 mL; P < .0001 and 50.5 ± 8.6 pg/mL vs 20.7 ± 3.8 pg/mL; P = .0001, respectively). A significant reduction in synovitis score (P = .0001), macrophage infiltration (P < .0003), M1/M2 ratio (P < .0007), angiogenesis (P < .0001), and the percentage of IL-1ß- and IL-6-positive cells in the intima (P < .008 and P < .002, respectively) was found after AKO. CONCLUSIONS: SF volume and IL-6 concentrations in the SF decreased and inflammatory synovium pathology improved after AKO. In addition to biomechanical changes, the biological environment of the joint can be improved after AKO. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

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.

Krüppel-like factor 15 deficiency exacerbates osteoarthritis through reduced expression of peroxisome proliferator-activated receptor gamma signaling in mice.

OBJECTIVE: Krüppel-like zinc finger transcription factors (KLFs) play diverse roles in mammalian cell differentiation and development. In this study, we investigated the function of KLF15 in the progression of osteoarthritis (OA). METHODS: 0Destabilization of the medial meniscus (DMM) surgery was performed in 10-week-old male wild-type control (WT) mice and cartilage-specific KLF15 knockout (KO) mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining were performed. Morphological changes were measured using microcomputed tomography. Six mice from each group were analyzed (total number of mice analyzed: 60). In vitro, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blot analyses were performed. RESULTS: KLF15 KO DMM mice exhibited significant cartilage degradation compared to WT mice. According to the Osteoarthritis Research Society International cartilage OA-histopathology scoring system, the mean sum score in KLF15 KO mice was significantly higher than that in WT mice at 8 weeks after surgery. Immunohistochemistry results revealed KLF15 KO mice exhibited reduced peroxisome proliferator-activated receptor gamma (PPARγ) expression, increased pIKKα/ß, a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) 5, and Matrix metalloproteinases (MMP13) expression, and reduced Forkhead box O (FOXO1) and Light chain 3B (LC3B) expression. Inhibition of PPARγ phosphorylation accelerated the effects of interleukin (IL) 1ß-treatment in both KLF15 KO and WT chondrocytes, and activation of PPARγ expression canceled the IL1ß-induced catabolic effects. CONCLUSION: Our results indicated that the OA phenotype of KLF15 KO DMM mice was influenced by reduced PPARγ expression, including enhanced pIKKα/ß, ADAMTS5, and MMP13 expression, reduced autophagy, and increased apoptosis. KLF15 regulation may constitute a possible therapeutic strategy for the treating OA.

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.

Pseudarthrosis of Pelvic Fracture With Charcot Arthropathy Successfully Treated With Constrained Total Hip Arthroplasty.

Charcot arthropathy is a rapidly progressive and destructive form of arthropathy caused by various neurological diseases. Total hip arthroplasty (THA) is usually contraindicated in patients with Charcot arthropathy; however, recent studies have reported good results following THA in this patient population. Herein, we report a case of Charcot arthropathy secondary to syphilis in a patient who was successfully treated with constrained THA, a new type of THA. A 56-year-old man was injured in a car accident, and a displaced acetabular fracture was revealed three weeks later. He was treated conservatively but soon developed greater displacement of the fracture and femoral head destruction. The patient was referred to our hospital for further treatment. The patient had pelvic pseudarthrosis secondary to Charcot arthropathy at the time of the first visit to our hospital. First, THA was performed with the acetabular reconstruction of the deficient bone. However, the acetabular implant was displaced one week postoperatively. THA revision was performed using a constrained cup. Postoperatively, the patient exhibited good hip stability without dislocation. However, displacement of the acetabular cup occurred one year after the second surgery. We performed a re-revision of THA using a new type of constrained cup that offers a high level of constraint to maintain range of motion (ROM) and prevent dislocations. The patient was able to walk with a T-cane one year postoperatively. Herein, we report a difficult case of revision THA in a patient with Charcot arthropathy concomitant with syphilis. THA is usually contraindicated in patients with Charcot arthropathy; however, we propose that THA using constrained cups that offer a wider ROM may be a useful therapeutic strategy for the treatment of Charcot arthropathy.

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.

C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration.

Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.

Phase III clinical trial of autologous CD34 + cell transplantation to accelerate fracture nonunion repair.

BACKGROUND: We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients. METHODS: CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded. RESULTS: All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16-6.85); moreover, no safety concerns were observed. CONCLUSIONS: Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion. TRIAL REGISTRATION: UMIN-CTR, UMIN000022814. Registered on 22 June 2016.

Comparison study of periprosthetic bone remodeling between simultaneous bilateral total hip arthroplasty and unilateral total hip arthroplasty: a matched cohort study.

PURPOSE: The load-bearing pattern of periprosthetic bone may differ between patients who underwent simultaneous bilateral and unilateral total hip arthroplasty (THA). We investigated the differences in periprosthetic bone remodeling after simultaneous bilateral total hip arthroplasty and unilateral total hip arthroplasty. METHODS: This retrospective cohort study enrolled 154 consecutive patients undergoing THA using full hydroxyapatite (HA) compaction short stems. Patient characteristics including age, body mass index, University of California Los Angeles (UCLA) activity score, and bone shape of the proximal femur were adjusted by propensity score matching. Subsequently, periprosthetic bone mineral density changes were compared between simultaneous bilateral and unilateral THA. RESULTS: We found that bone mineral density loss in the simultaneous bilateral THA group was significantly higher in zones 6 and 7 at 24 months after THA (zone 6, p = 0.019; zone 7, p = 0.041). Periprosthetic bone mineral density loss was not associated with clinical factors, including age, body mass index, and daily activity. Additionally, we demonstrated that periprosthetic bone mineral density loss was higher in zones 1, 4, 6, and 7 of patients with a normal hip on the contralateral side after unilateral THA (zone 1, p = 0.041; zone 4, p = 0.041; zone 6, p = 0.037; zone7, p = 0.019). CONCLUSIONS: The postoperative periprosthetic bone remodeling was lower in patients who underwent simultaneous bilateral THA than in those who underwent unilateral THA, even though patient characteristics were adjusted by propensity matching. Further observation of periprosthetic bone mineral density loss is needed to clarify the differences between the groups.

Clinical and Radiological Comparison of Single and Double Intra-articular Injection of Adipose-Derived Stromal Vascular Fraction for Knee Osteoarthritis.

The aim of the article is to compare the clinical and radiological outcomes between single and double stromal vascular fraction (SVF) cell injections in patients with knee osteoarthritis (OA). We included 54 patients treated for varus knee OA with intra-articular SVF cell injection. They were divided into two groups: those who received one injection and those who received two. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, knee range of motion, and knee muscle force were assessed at baseline and 3, 6, 12, and 24 months after the first injection. The preoperative hip-knee-ankle (HKA) angle was evaluated using plain radiographs, and T2 mapping values were assessed. The total WOMAC score improved significantly in the single injection group from 3 to 24 months, but the total WOMAC score in the double injection group improved significantly at 24 months. The T2 mapping values in both the groups improved, with a significant difference at 12 months. The preoperative mean HKA angle and the correlation coefficients between the HKA angle and the total WOMAC score and between the HKA angle and the T2 mapping value of the medial femur were significant. In conclusion, double injections may provide more satisfactory treatment outcomes in patients with severe varus knee alignment. This clinical trial is registered in the Japanese Ministry of Health, Labour and Welfare (URL: https://saiseiiryo.mhlw.go.jp/published_plan/index/2) with the registration name "Cell transplantation therapy for osteoarthritis using autologous subcutaneous adipose tissue-derived regenerative (stem) cells (ADRCs)," and the registration number was "PB5160012."

Accuracy comparison of cup positioning during total hip arthroplasty using Hip Align and AR-Hip in the supine position.

INTRODUCTION: The aim of this study is to compare the accuracy of acetabular cup positioning between the accelerometer-based navigation system and the augmented reality-based navigation system during THA in the supine position. MATERIALS AND METHODS: This retrospective study included 66 patients (70 hips) who underwent THA using two types of portable navigation system, Hip Align or AR-Hip, in the spine position. The absolute difference between the intraoperative navigation record and postoperative measurement using computed tomography data was evaluated. Preoperative clinical factors that decreased the accuracy of cup positioning by ≥ 3° were analyzed via multiple logistic regression analyses. RESULTS: The average absolute error of inclination was 2.8 ± 2.6° in Hip Align and 2.7 ± 1.8° in AR-Hip, and absolute anteversion error was 2.5 ± 2.0° in Hip Align and 2.6 ± 2.2° in AR-Hip, and there was no significantly different between the two navigation systems. There was a significant association between the absolute measurement error (≥ 3°) of cup inclination and patients' BMI in the Hip Align group [odds ratio (OR) 1.350; 95% confidence interval (CI) 1.035-1.760; p = 0.027], but not in the AR-Hip group. CONCLUSIONS: The accuracy of the acetabular cup positioning between the Hip Align and AR-Hip showed no difference during THA in the spine position. The high BMI could have negative influence on the accuracy of cup positioning in THA using Hip Align, thus AR-Hip could be designable for obesity patients.