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.
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.
CONCLUSIONS: 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.
METHODS: Level III, retrospective case-control study.

BACKGROUND: This study aimed to detect medial meniscal posterior root tear (MMPRT) diagnostic methods with high sensitivity and specificity using dynamic ultrasonographic evaluation in patients with early knee osteoarthritis (OA) and demonstrate the usefulness of dynamic ultrasonographic medial meniscal extrusion (MME) evaluation in MMPRT diagnosis using a cutoff value.
METHODS: Between 2018 and 2020, a total of 120 patients were diagnosed with early knee OA using clinical and radiographic findings. Dynamic ultrasonographic evaluations and magnetic resonance imaging were performed in all patients, and 47 patients who had and 73 patients who did not have MMPRT were classified into the MMPRT and non-MMPRT groups, respectively. Age, sex, femorotibial angle, MME of knee extension and flexion, and MME at weight-bearing were compared between the two groups. Additionally, the sensitivity and specificity of significant ultrasonographic findings were calculated using a receiver operating characteristic (ROC) curve.
RESULTS: The MMEs under knee extension-flexion and weight-loading in the MMPRT group were significantly larger than those in the non-MMPRT group. ROC curve analysis for each ultrasonographic evaluation condition to diagnose MMPRT indicated that the sensitivity was 72-88% and the specificity was 66-85% when the cutoff values of MME under knee flexion at 0°, 90°, and weight-loading were set at 2.55 mm, 2.00 mm, and 3.55 mm, respectively. The highest sensitivity (88%) and specificity (85%) were exhibited upon > 2 mm MME at a knee flexion of 90° and were the most useful indicators for MME diagnosis.
CONCLUSIONS: Ultrasonographic MME evaluations for MMPRT diagnosis showed relatively high sensitivity and specificity in patients with early knee OA. Dynamic ultrasonographic MME evaluation may lead to appropriate additional examinations, early diagnosis, and intervention for MMPRT in patients with early knee OA.

BACKGROUND: Whether the medial meniscus morphology and movement occur under upright loading conditions in early knee osteoarthritis (OA) or medial meniscus posterior root tear (MMPRT) remains unknown. This study aimed to evaluate the medial and anteroposterior extrusion of the medial meniscus under unloaded and upright-loaded conditions in patients with early knee OA.
METHODS: Twelve patients with early knee OA and 18 healthy adult volunteers participated in this study. Magnetic resonance imaging using special equipment was performed with the participants in the unloaded and upright-loaded conditions. Medial, anterior, and posterior extrusions of the medial meniscus against the tibial edge were evaluated and compared between the early knee OA and healthy adult control groups. Additionally, 12 patients in the early knee OA group were divided into 2 subgroups based on whether MMPRT was observed, and the extrusion of the medial meniscus was compared.
RESULTS: The amount of medial extrusion of the medial meniscus in both the unloaded and upright-loaded conditions was significantly greater in the early knee OA group than in the control group (unloaded: 2.6 ± 1.0 mm vs 0.7 ± 0.5 mm; upright-loaded: 3.7 ± 0.9 mm vs 1.8 ± 0.8 mm). Similarly, the anterior and posterior extrusion of the medial meniscus in the upright-loaded condition was significantly larger in the early knee OA group (anterior: 4.6 ± 1.0 mm vs 3.7 ± 1.1 mm; posterior: -3.4 ± 1.1 mm vs -4.6 ± 1.6 mm). However, no difference was observed in meniscal extrusion between unloaded and upright-loaded conditions. The posterior extrusion of the medial meniscus in the upright-loaded condition was significantly greater in MMPRT cases than in non-MMPRT cases in the early knee OA group (MMPRT: -2.7 ± 1.1 mm; non-MMPRT -4.1 ± 1.5 mm).
CONCLUSIONS: In early knee OA, significantly large meniscal extrusions of the medial meniscus in both unloaded and upright-loaded conditions were found compared with healthy adults. Among patients with early knee OA, those with MMPRT showed a large posterior extrusion of the medial meniscus in the upright-loaded condition compared with those without MMPRT.
METHODS: Level IV.

The characteristics of muscle degeneration in individual quadriceps in early knee osteoarthritis (OA) and the association of muscle quantity and quality on knee dysfunction remain unclear. This study aimed to clarify the characteristics of muscle degeneration in individual quadriceps muscles in early knee OA and elucidate the association of muscle volume and intramuscular adipose tissue (intraMAT) with knee dysfunction, including functional disabilities, symptoms, and joint morphology.
Fifty participants were categorized into early knee OA and healthy control groups. 3.0 T magnetic resonance imaging (MRI) using T1-weighted and Dixon methods and 3D SPACE in the thigh muscle and knee joint regions was performed. Quadriceps muscle volume, intraMAT, and whole-organ MRI score (WORMS) were assessed. The Knee Society Score (KSS) was used to evaluate functional disabilities and knee symptoms. Univariate analysis of variance was conducted with covariates to clarify the differences in muscle volume and intraMAT between the two groups. Multiple linear regression analyses were performed using the KSS function and symptom subcategories and WORMS as dependent variables and muscle volume, intraMAT, and the presence of early knee OA as independent variables, such as potential confounders.
The quadriceps intraMAT, especially in the vastus medialis (VM), was significantly higher in patients with early knee OA than in healthy controls. The VM intraMAT, not muscle volume, was significantly associated with KSS function [B =  - 3.47; 95% confidence interval [CI], - 5.24 to - 1.71; p < 0.001] and symptom scores [B =  - 0.63; 95% CI, - 1.09 to - 0.17; p = 0.008], but not with WORMS.
These findings suggest that higher VM intraMAT is characteristic of quadriceps muscle degeneration in early knee OA and its increase is associated with functional disabilities and symptoms.

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).
CONCLUSIONS: Knee effusion may be an indicator of the progression of early-stage knee OA.

Patients with knee osteoarthritis show low stair climbing ability, but a diagnosis of stair performance time is not enough to identify the early stages of knee osteoarthritis. Therefore, we developed an indicator named range of the knee joint trajectory (RKJT) as a kinematic parameter to express more detailed characteristics than stair performance time. To achieve this, we used our developed \"IR-Locomotion\", a markerless measurement system that can track the knee joint trajectory when climbing stairs. This study aimed to test whether the RKJT effectively identifies patients with early knee osteoarthritis even after controlling stair performance time. Forty-seven adults with moderate to severe knee pain (mean age 59.2 years; 68.1% women) underwent the radiographic examination (Kellgren and Lawrence grade) of both knees and a stair climbing test on 11 stairs. The RKJT during the stair climbing test was calculated by \"IR-Locomotion\". A generalized linear mixed model was used to evaluate the discriminative capability of RKJT on early knee osteoarthritis (i.e., Kellgren and Lawrence grade of 1). As expected, patients with early knee osteoarthritis showed larger RKJT than non-radiographic controls (95% confidence interval: 1.007, 1.076). Notably, this finding was consistent even after adjusting stair performance time.

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

Radiographic changes in knee osteoarthritis (OA) are not always associated with symptoms, especially in its early stages. Ultrasonography (US) can detect early changes in the knee joint, but the changes that reflect symptoms have not been fully elucidated. This study aimed to identify US-detectable changes in the knee that are often associated with knee symptoms and demonstrate the feasibility of early diagnosis in symptomatic knee OA using US.
In this cross-sectional community-based study, 1,667 participants aged ≥60 years (1,103 women [66%]) were included. All participants concurrently underwent US and radiography of the knee and completed the Knee Society Knee Scoring System (KSS) questionnaire. Simple and multiple regression analyses were used to examine the associations between US findings and KSS symptom subscales.
Among all participants, medial meniscus protrusion and medial osteophytes, age, and body mass index showed significant associations with KSS symptom scores. Among 894 participants with Kellgren-Lawrence (KL) grade ≤1, medial osteophytes and age were significantly associated with KSS symptom score. US measures were more related to KSS symptoms than KL grades.
Among the knee US-detectable changes, medial osteophytes were strongly associated with knee symptoms. Osteophytes are reliable predictors of symptomatic early knee OA, even in participants with few radiographic OA changes.

BACKGROUND: Biomarkers of bone and cartilage metabolism were proposed as early diagnosis indicators for knee osteoarthritis (OA), however, which were influenced by disease stage, age, and menopause state. Accurate diagnosis indicators are eagerly awaited. The current study aims to investigate associations of joint metabolism biomarkers and bone mineral density (BMD) with early knee OA in males and premenopausal females before age 50 years.
METHODS: A total of 189 patients aged before 50 years with early knee OA and 152 healthy participants were enrolled. Levels of bone biomarkers (PINP, OC, and CTX-I) and cartilage biomarkers (PIIANP, COMP, CTX-II, and MMP-3) were assessed. BMD was measured at the lumbar, femoral neck, and hip. Multivariate regression analyses were performed to evaluate the relationship between biomarkers, BMD, and early knee OA.
RESULTS: Serum COMP, urine CTX-II and BMD at femoral neck and hip were increased in premenopausal patients as compared to control; with serum PINP and OC reduced. Meanwhile, serum COMP, urine CTX-II, and BMD at femoral neck and hip showed positive associations with premenopausal early knee OA, while serum PINP had negative association. However, in male patients, only serum COMP was higher than control, and no association of biomarkers or BMD was found with early knee OA.
CONCLUSIONS: The joint metabolism biomarkers and BMD showed multiple associations with early knee OA in premenopausal females, but not in males aged before 50 years. It was suggested that sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. Key Points • The joint metabolism biomarkers and BMD are associated with early knee OA in premenopausal females, but not in males aged before 50 years. • Sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA.

OBJECTIVE: To investigate the association between serum biomarker [cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP-3)] levels and clinical, magnetic resonance imaging (MRI), and arthroscopic findings in anterior cruciate ligament (ACL)-deficient knees without osteoarthritic changes on radiographs.
METHODS: Patients with ACL injury of Kellgren-Lawrence grade 0 or 1 were enrolled. Serum COMP and MMP-3 levels were measured preoperatively. Correlations of serum biomarker levels with age, body mass index (BMI), duration from time of injury, Tegner activity scale (TAS) score, Lysholm knee score, International Knee Documentation Committee score, KT-1000 arthrometer measurements, whole-organ MRI score (WORMS), MRI T2 relaxation time, and arthroscopic International Cartilage Research Society (ICRS) grade were assessed by calculating Spearman correlation coefficients. Associations between intraoperative findings (cartilage, meniscus) and serum biomarker levels were determined using the Mann-Whitney U test. Multiple regression analysis was performed to investigate the correlations between serum biomarker levels and MRI and arthroscopic findings.
RESULTS: Ninety-eight patients with a mean age of 23.7 years were enrolled. Higher serum COMP level was correlated with older age and higher BMI, TAS score, serum MMP-3 level, WORMS, and T2 relaxation times (medial femur, medial tibia). Multivariate analysis showed that the serum COMP level was independently associated with WORMS and ICRS grade.
CONCLUSIONS: The serum COMP level was correlated with age, BMI, TAS score, and MMP-3 level in ACL-deficient knees and was independently correlated with WORMS and ICRS grade. Thus, the serum COMP level can help detect cartilage degeneration even in patients without radiographic osteoarthritic changes. Key Points • Serum COMP correlated with WORMS and ICRS grade in ACL deficient knee. • The serum COMP level could help in detecting cartilage degeneration, even in patients with no radiographic osteoarthritic changes.