Greater medial proximal tibial slope is associated with bone marrow lesions in middle-aged women with early knee osteoarthritis.

BACKGROUND: Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on BML, including the spreading root sign (SRS), in women without radiographic knee osteoarthritis (OA). It was hypothesized that varus alignment and a greater posterior tibial slopes (PTS) are associated with BML. MATERIALS AND METHODS: A total of 359 female volunteers without knee OA who were participants in the Iwaki Health Promotion Project in 2017 or 2019 were enrolled. Participants were divided into the non-OA and early knee OA (EKOA) groups based on the Luyten's classification criteria. The presence of pathological cartilage lesions, BMLs, attritions, meniscal lesions and effusions was scored on T2-weighted fat-suppressed magnetic resonance imaging (MRI) according to the Whole-Organ MRI Scoring system. The medial proximal tibial angle (MPTA) and medial and lateral PTS (MPTS and LPTS, respectively) were measured. Regression and receiver operating characteristic (ROC) analyses were performed to reveal the relationship between BMLs and proximal tibial morphological parameters. RESULTS: Of the 359 participants, 54 (15%) were classified as having EKOA. The prevalence of cartilage lesions, BMLs, attritions, meniscal lesions and effusions was higher in the EKOA group than in the non-OA group. The two groups had no significant difference in the proximal tibial parameters. Regression analysis revealed that age and a smaller MPTA were associated with BML in both groups. Attrition (p = 0.029) and the MPTS (p = 0.025) were positively associated with BML in the EKOA group. CONCLUSION: The prevalence of BMLs was higher in women with EKOA and correlated with the varus and greater posterior slopes in those without radiographic knee OA. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Single-cell transcriptome analysis reveals cellular heterogeneity in mouse intra- and extra articular ligaments.

Ligaments are collagenous connective tissues that connect bones. Injury of knee ligaments, namely anterior cruciate ligament (ACL) and medial collateral ligament (MCL), is common in athletes. Both ligaments have important functions, but distinct regeneration capacities. The capacity for recovery after injury also diminishes with age. However, cellular heterogeneity in the ligaments remains unclear. Here, we profiled the transcriptional signatures of ACL and MCL cells in mice using single-cell RNA sequencing. These ligaments comprise three fibroblast types expressing Col22a1, Col12a1, or Col14a1, but have distinct localizations in the tissue. We found substantial heterogeneity in Col12a1- and Col14a1-positive cells between ACL and MCL. Gene Ontology analysis revealed that angiogenesis- and collagen regulation-related genes were specifically enriched in MCL cells. Furthermore, we identified age-related changes in cell composition and gene expression in the ligaments. This study delineates cellular heterogeneity in ligaments, serving as a foundation for identifying potential therapeutic targets for ligament injuries.

Effusion detected by ultrasonography and overweight may predict the risk of knee osteoarthritis in females with early knee osteoarthritis: a retrospective analysis of Iwaki cohort data.

BACKGROUND: Knee osteoarthritis (OA) has enormous medical and socioeconomic burdens, which early diagnosis and intervention can reduce. We investigated the influence of knee effusion on the progression of knee OA in patients with early knee OA. METHODS: A total of 404 participants without radiographic knee OA were assessed from a 3-year longitudinal analysis. Participants were classified into non-OA and early knee OA groups. The effusion area (mm2) was quantified using ultrasonography. Receiver operating characteristic and logistic regression analyses were performed. RESULTS: At the 3-year follow-up, 114 of 349 knees (32%) had progressed from non-OA and 32 of 55 knees (58%) had progressed from early knee OA to radiographic knee OA. Logistic regression analysis showed that female sex (odds ratio [OR] 3.36, 95% confidence interval [CIs] 2.98-5.42), early knee OA (OR 2.02, 95% CI 1.08-3.75), body mass index (OR 1.11, 95% CI 1.02-1.19), and effusion area (OR 1.01, 95% CI 1.01-1.02) were significantly correlated with knee OA progression. Women who were overweight (body mass index ≥ 25 kg/m2) with more severe effusion had a higher risk of OA progression (area under the curve = 0.691, OR = 6.00) compared to those not overweight (area under the curve = 0.568, OR = 1.91). CONCLUSION: Knee effusion may be an indicator of the progression of early-stage knee OA.

Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study.

BACKGROUND: Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. METHODS: We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. RESULTS: Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7). CONCLUSION: Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

A Novel Quantitative Evaluation of Bone Formation After Opening Wedge High Tibial Osteotomy Using Tomosynthesis.

This study aimed to establish and validate a novel evaluation method using digital tomosynthesis to quantify bone formation in the gap after opening wedge high tibial osteotomy (OW-HTO). We retrospectively analyzed bone formation in the gap in 22 patients who underwent OW-HTO using digital tomosynthesis at 1, 2, 3, 6, 9, and 12 months postoperatively. Bone formation was semi-quantitatively assessed using the modified van Hemert's score and density measurements on digital tomosynthesis images. The gap filling value (GFV) was calculated as the ratio of the intensities of the opening gap and the tibial shaft. In addition, the relationship between the modified van Hemert's score and GFV was evaluated. The reproducibility of GFV had an interclass correlation coefficient (ICC [1,2]) of 0.958 for intraobserver reliability and an ICC (2,1) of 0.975 for interobserver reliability. The GFV increased in a time-dependent manner and was moderately correlated with the modified van Hemert's score (r = 0.630, p < 0.001). The GFV plateaued at 6 months postoperatively. In addition, the GFV was higher in patients with a modified van Hemert's score of 2 than in patients with a modified van Hemert's score of 3 (p = 0.008). The GFVs obtained using digital tomosynthesis can be used to assess postoperative bone formation in the opening gap after OW-HTO with high accuracy and reproducibility.

Bone marrow lesion severity was associated with proximal tibial inclination in early knee osteoarthritis.

PURPOSE: This study aimed to investigate the effect of tibial plateau (TP) inclination and serum bone metabolic markers on bone marrow lesion (BML) in the general Japanese population with early knee osteoarthritis (EKOA). METHODS: A total of 441 female volunteers who participated in the Iwaki Health Promotion Project in 2017 were enrolled. Participants without radiographic abnormalities were divided into normal and EKOA groups according to the Luyten's classification criteria for EKOA. The medial proximal tibial angle (MPTA), growth plate-TP angle, and growth plate-medial tibial plateau (MTP) angle were measured on standing anteroposterior radiographs of the knees. BML severity on T2-weighted fat-suppressed magnetic resonance imaging (MRI) was scored using the Whole-Organ MRI Score method. Serum levels of N-telopeptide of type I collagen, tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, pentosidine, and homocysteine were assessed. Linear regression analysis was conducted to investigate the relationship between proximal tibial inclination, BML, and serum bone metabolic markers. RESULTS: The growth plate was observed in 309 (70%) participants, and 48 (16%) participants had EKOA. The mean MPTA, growth plate-TP angle, and growth plate-MTP angle were 86.1 ± 5.9°, 3.6 ± 1.1°, and 9.9 ± 2.6°, respectively. The MPTA was negatively correlated with the growth plate-TP and growth plate-MTP angles (p = 0.006, p < 0.001). Participants with EKOA who had BML exhibited greater growth plate-MTP angle than those who did not (p = 0.018). Regression analysis revealed that BML severity was positively associated with MPTA (p = 0.036) and a bone formation marker (p = 0.045). CONCLUSION: BML severity was positively associated with proximal tibial inclination and serum TRACP-5b level in participants with EKOA and normal knees, respectively. Assessment of proximal tibial inclination may provide insight into potential BML risk. Residual medial tibial inclination may potentially result in knee pain and symptoms in EKOA. LEVEL OF EVIDENCE: III.

Detection of synovitis in early knee osteoarthritis by MRI and serum biomarkers in Japanese general population.

To investigate synovitis' influence on early knee osteoarthritis (EKOA) by serum biomarkers and magnetic resonance imaging (MRI) findings in Japanese women. We enrolled 255 women aged 30-70 without radiographic abnormalities (Kellgren-Lawrence grade ≥ 2). Knee injury, OA outcome scores (KOOS), clinical examinations, and standing radiograph were used for classification criteria of EKOA. Participants were classified into normal knee group and EKOA group. All participants underwent MRIs of their right knee. The amount of effusion-synovitis volume was quantified. We compared serum matrix metalloproteinases-3 levels (MMP-3), high-sensitivity C-reactive protein, interleukin-6, and adiponectin between the groups. The relationship between synovitis and EOKA was investigated using multiple linear regression. Fifty-four participants (21%) were classified as EKOA. Serum MMP-3 concentration and effusion-synovitis volume were higher in patients with EKOA (p = 0.025 and p = 0.001, respectively). Effusion-synovitis volume negatively correlated with all KOOS subscales and positively correlated with serum MMP-3 concentration. Serum MMP-3 concentration was associated with effusion-synovitis volume ß = 0.60, p < 0.001). There was mildly active but definitive synovitis in EKOA. This was an observational study so that no conclusions can be drawn regarding cause-effect for synovitis and symptoms. Future studies should conduct follow-up of participants with synovitis to assess the progression of knee OA.

Valgus Correctability and Meniscal Extrusion Were Associated With Alignment After Unicompartmental Knee Arthroplasty.

BACKGROUND: Appropriate postoperative lower limb alignment is one important element of a successful unicompartmental knee arthroplasty (UKA). To predict postoperative alignment, it is important to investigate the association between preoperative imaging evaluations and lower limb alignment after medial UKA. QUESTIONS/PURPOSES: (1) Do preoperative valgus stress radiographic and MRI measurements (% mechanical axis, hip-knee-ankle angle, medial meniscal extrusion distance, and osteophyte area at the medial femur and tibia) correlate with postoperative lower limb alignment after UKA; and (2) Can useful cutoffs be calculated in advance of surgery for those findings that were associated with coronal-plane overcorrection? METHODS: We retrospectively analyzed 125 patients with medial knee pain who underwent UKA from January 2012 to October 2018. Valgus stress radiography and MRI were performed routinely to assess the knee. Valgus stress radiography was obtained with the patient supine with the knee in full extension and a firm manual valgus force applied to the knee. Full-length weightbearing radiography was performed 3 months after surgery. There were 12% (15) of patients who did not undergo MRI, and 4% (five) of patients who did not receive the postoperative full-length weightbearing radiograph and they were excluded, leaving 84% (105) of patients available for analysis. There were 27 men and 78 women with a mean (range) age of 77 years ± 6 years (60 to 87). The preoperative diagnosis was medial osteoarthritis in 99 patients and osteonecrosis of the medial femoral condyle in six. To investigate the associations, we routinely measured % mechanical axis using radiography, and also measured the medial meniscal extrusion distance and osteophyte area at the medial femur and tibia using MRI after surgery. Medial meniscus extrusion distance was defined as the distance from the outermost edge of the medial meniscus to a line connecting the femoral and tibial cortices. From these parameters, postoperative alignment was estimated using regression and receiver operating characteristic curve analyses. Variables with p < 0.05 were included. RESULTS: The % mechanical axis on the valgus stress radiograph and medial meniscal extrusion distance were correlated with postoperative lower limb alignment after UKA (adjusted correlation coefficient 0.72; p < 0.001, adjusted correlation coefficient 0.2; p = 0.003, respectively). The estimated % mechanical axis on the postoperative weightbearing radiograph was equal to -0.27 + 0.86% (% mechanical axis on valgus stress radiograph) + 1.14 mm (medial meniscal extrusion distance). Using a cutoff point of 36%, the % mechanical axis on valgus stress radiograph was associated with overcorrection after UKA (area under the curve: 0.89; odds ratio 14 [95% CI 0.75 to 0.95]; p < 0.001, sensitivity 77.8%, specificity 80.9%). CONCLUSIONS: The overcorrection of a varus knee on a valgus stress radiograph before UKA and the increased extrusion of the medial meniscus on preoperative MRI was associated with a greater likelihood of overcorrected alignment after UKA. Future studies should conduct long-term follow-up of malalignment patients to assess the possible complications. LEVEL OF EVIDENCE: Level III, diagnostic study.

Medial stabilizing technique preserves anatomical joint line and increases range of motion compared with the gap-balancing technique in navigated total knee arthroplasty.

BACKGROUND: Medial compartment stability is important in total knee arthroplasty. The medial stabilizing technique (MST) has been proposed to achieve medial stability without excessive medial soft tissue release in total knee arthroplasty. Herein, we compare the MST and the gap-balancing technique (GBT) in navigated total knee arthroplasty. METHODS: We retrospectively analyzed 70 patients with varus knee osteoarthritis who underwent primary total knee arthroplasty using the navigation system. They were divided into MST (n = 39) and GBT (n = 31) groups. We assessed intraoperative navigation data, radiographic data, and insert thickness. Preoperative and postoperative joint line changes were measured. We also assessed range of motion and clinical instability before and after total knee arthroplasty. These parameters were statistically compared between the groups. RESULTS: Compared with the GBT group, medial extension gaps were significantly smaller in the MST group (P = 0.008). The gap difference between medial and lateral extension was significantly greater in the MST group (P = 0.018). Other navigation data showed no significant differences. Insert thickness and joint line changes were significantly lower in the MST group (P = 0.001, P = 0.018, respectively). Postoperative range of motion was significantly greater in the MST group (P = 0.032). There was no objective or subjective knee instability in either group. CONCLUSION: The MST could avoid knee joint line changes and might increase postoperative range of motion. Although the MST permitted a discrepancy between medial and lateral gaps, no patients felt knee instability. The MST might improve the results of total knee arthroplasty.

Posterior clearance increases the knee extension angle in cruciate retaining type total knee arthroplasty: Intraoperative evaluation using a navigation system.

BACKGROUND: Posterior osteophyte of the femur can impinge on the tibia insert in total knee arthroplasty (TKA). Although osteophyte removal [posterior clearance (PC)] improves the flexion angle, its influence on the gaps and extension angle are unclear. This study investigated the effect of PC on the gaps and range of motion (ROM) using a navigation system, as well as PC's relationship with osteophyte size. METHODS: Twenty-seven knees that underwent cruciate-retaining (CR)-type TKA were examined. Before and after PC, the ROM, hip-knee-ankle (HKA) angle, and flexion and extension gaps were recorded using a navigation system. Osteophyte size was measured in the lateral view in radiographs, and in the sagittal and axial planes of computed tomography (CT) images. The effects of PC on the gaps and ROM were analysed statistically. RESULTS: PC caused the extension gap to increase by 0.7 ± 0.9 mm in the medial (p < 0.001), and 0.9 ± 1.5 mm in the lateral compartment (p = 0.006). The extension angle increased by 4.9 ± 1.6°, flexion angle increased by 6.5 ± 5.0°, and HKA decreased by 0.3°. The increase in extension angle by PC was significantly correlated with the preoperative HKA angle (r = 0.594) and with the osteophyte area in radiographs and CT (r = 0.626 to 0.681). CONCLUSIONS: The extension and flexion gaps increased less than 1 mm in the medial and lateral compartments. PC achieving an additional 5° extension angle could promote full extension in severely deformed knees with a large posterior osteophyte. The extension angle increase by PC was correlated with the preoperative HKA angle and osteophyte size.