Bone Marrow Lesions Research Articles

Exercise and footwear in medial knee osteoarthritis: a randomized controlled trial comparing flat flexible footwear to stable supportive shoes

Abstract Objective This randomized controlled trial (RCT) investigated whether adding daily use of flat flexible footwear (FFF) to a strengthening and aerobic exercise programme improved short- and longer-term outcomes compared to adding stable supportive shoes (SSS) in people with medial tibiofemoral osteoarthritis (OA). Methods Participants (n = 97) with medial tibiofemoral OA were randomly assigned (1:1) to FFF (n = 50) or SSS (n = 47) group. Participants in both group received a 9-month intervention (3 months supervised followed by 6 months unsupervised exercise). The primary outcome was change in knee pain on walking at 3 months measured using a 11-point numeric rating scale (NRS). Secondary outcomes included change from baseline to 3 and 9 months in severity of knee pain overall (NRS), physical function (WOMAC subscale), habitual physical activity level (PASE), quality of life (QoL) (EQ-5D-5L), and markers of inflammation (Effusion- and Hoffa-synovitis) and structural disease progression (bone marrow lesions (BMLs)). Results There were no significant differences between the groups in the change in pain on walking (between-group difference, -0.67 [95% CI, -1.62 to 0.29]) at 3 months. Knee pain on walking and overall knee pain significantly decreased in both groups at 3 months and 9 months. Physical function and QoL improved in both groups at 3 months and at 9 months. We found no between-group differences in any secondary outcome at any time. Conclusions FFF added to exercise therapy did not provide additional better symptom- nor structure-modification benefit compared to conventional SSS and exercise in people with medial tibiofemoral OA. Clinical trial registration number ClinicalTrials.gov (NCT03796832)

Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage Loss.

To assess whether change of semiquantitatively magnetic resonance imaging (MRI)-defined bone marrow lesions (BMLs) and inflammatory markers is associated with change in quantitatively-assessed cartilage loss in the femorotibial joint (FTJ) in knees with radiographic osteoarthritis (OA) over 24 months. Participants were included from the IMI-APPROACH and the Osteoarthritis Initiative FNIH studies. Semiquantitative MRI assessment was performed for BMLs, Hoffa- and effusion-synovitis. Quantitative cartilage thickness measurements were performed manually. Definitions of change included number of subregions with BMLs, change in sum and change in maximum increase in size. Change in Hoffa-synovitis and effusion-synovitis was categorized in addition. Between-group comparisons regarding cartilage loss in the FTJ, medial and lateral compartments were performed using analysis of variance (ANOVA). A total of 629 participants were included. Knees without any BMLs at baseline (BL) and follow-up (FU) had significantly less cartilage loss compared to the other subgroups. Change in both directions in the sum score of BMLs was associated with increased rates of cartilage loss. Maximum increase in size of BMLs was associated with increased rates of cartilage loss (FTJ increase by 2 grades -0.183 mm, 95% CI [-0.335, -0.031], by 3 grades -0.306 mm, [-0.511, -0.101]). Worsening of Hoffa-synovitis was associated with increased rates of cartilage loss. Knees without BMLs at BL and FU showed lowest rates of cartilage loss. Knees with an increase in BML size showed increased rates of concurrent cartilage loss. Approaches with the aim to inhibit BML development, avoidance of increase in size and avoidance of Hoffa-synovitis worsening may have beneficial effects on cartilage loss.

Chemoprotective Effect of Eugenol on Repeated dose Doxorubicin, Induced Genotoxic Lesions in Mouse Bone Marrow

In present study, an attempt has been made to evaluate the possible in vivo chemoprotective potential of eugenol against doxorubicin induced genotoxic lesion in bone marrow. Swiss albino female mice were administered Eugenol (10 mg/kg/day, orally) 15 days before doxorubicin administration as well as concomitantly with doxorubicin. Genotoxic lesions were induced by a repeated dose intraperitoneal injection of doxorubicin (5mg/kg b.w. i.p. upto 9 days (alternate day). Micronuclei assay and COMET assay were carried out to determine genetic damage in bone marrow. Histopathological evaluation of bone marrow was also done to study lesions at cellular level. The study results demonstrated that eugenol significantly mitigated Doxorubicin induced micronuclei formation and DNA damage in the bone marrow niche. Histopathological observations revealed that Doxorubicn-intoxication resulted in massive structural impairment of bone marrow which was reduced by eugenol administration. Amelioration by eugenol is more significant in mice those received eugenol 15 days prior to Doxorubicin administration suggesting its chemoprotection. The present study suggests eugenol has the promising chemoprotective effect against Doxorubin-induced genetic lesions in mice bone marrow.

Blood flow signals through the bone cortex on ultrasonography can be used as a screening test for detecting bone marrow lesions on magnetic resonance imaging in patients with early knee osteoarthritis.

Blood flow signals (BFSs) through the bone cortex on ultrasonography (US) and bone marrow lesions (BMLs) detected on magnetic resonance imaging (MRI) can be used to assess bone lesions; however, no studies have reported their relationship. Therefore, this study aimed to assess whether BFSs through the bone cortex on US can serve as a screening test for detecting BMLs on MRI in patients with early knee osteoarthritis (OA). This study enrolled patients with knee joint pain who were diagnosed with early knee OA between January 2018 and January 2024. We targeted 77 patients who underwent MRI and in whom the presence or absence of BFSs through the bone cortex was confirmed on US. The association between BFSs and BMLs was evaluated using the chi-square test, and the sensitivity and specificity of BFSs for detecting BMLs on MRI were calculated. The chi-square test showed that BFSs and BMLs were significantly associated in the femur and tibia (femur: χ2 [1] = 52.9, p < 0.001; Tibia: χ2 [1] = 44.8, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of BFSs for detecting BMLs on MRI were 85.0%, 96.5%, 89.5%, and 94.8%, respectively, for the femur, and 84.0%, 92.3%, 84.0%, and 92.3%, respectively, for the tibia. BFSs through the bone cortex on US can be used as a screening test for detecting BMLs on MRI in patients with early knee OA.

Assessment of chemical-shift and diffusion-weighted magnetic resonance imaging in differentiating malignant and benign vertebral lesions in oncologic patients. A single institution experience.

To analyze the contribution of two non-standard magnetic resonance imaging (MRI) techniques the chemical-shift image (CSI), and diffusion-weighted imaging (DWI) in distinguishing malignant and benign vertebral bone marrow lesions (VBMLs). Conventional spine MRI protocol, followed by CSI and DWI was performed with a 1.5 T system on 102 oncologic patients between January 2020 and December 2023. From the identified 325 VBMLs, 102 representative lesions (one per patient) were selected. VBMLs were divided into malignant (n = 74) and benign (n = 28) based on histopathology, or imaging follow-up. The quantitative parameters for VBMLs assessment were signal intensity ratio (SIR) derived from CSI and apparent diffusion coefficient (ADC) derived from DWI. The malignant VBMLs had significantly higher SIR values (p < 0.05) and lower ADC values compared to benign VBMLs (p < 0.05). The area under the curve (AUC) was 0.953 (p < 0.001) for SIR, and 0.894 for ADC (p < 0.001) (cut-off at > 0.82, and ≤ 1.57x10-3 mm2/s, respectively). The sensitivity and specificity for SIR were 93.6%, and 88.5%, while for ADC were 88.2% and 92.3% (respectively). The combined use of SIR and ADC improved the diagnostic accuracy to AUC of 0.988 (p < 0.001, cut-off at > 0.19), sensitivity, and specificity of 100.0% and 90.9% (respectively). Quantitative parameters, SIR and ADC, derived from two non-standard MRI techniques, CSI, and DWI, showed diagnostic strength in differentiating malignant and benign VBMLs. Combining both methods can further enhance the diagnostic performance and accuracy of spine MRI in clinical practice.

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study

BackgroundPreventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2–5 years...

Head to head comparison of 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging used in diagnosis of autoimmune rheumatic diseases.

The aim of this study was to determine the performance of radionuclide-labeled fibroblast activation protein inhibitors (Al18F-NOTA-FAPI-04) PET/CT in patients with autoimmune rheumatic diseases (ARDs) and compare it with fluorine-18 (18F) labeled fluorodeoxyglucose (FDG) imaging. Fifty-eight participants with ARDs were prospectively enrolled from April 2022 to February 2024 and underwent dual-tracer PET/CT imaging. For both 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT, imaging findings were interpreted and compared. The clinical significance was compared between18F-FDG PET/CT and Al18F-NOTA-FAPI-04 PET/CT imaging. 18F-FDG imaging was positive in 53 out of 58 cases (91.4%) while Al18F-NOTA-FAPI-04 imaging was positive in 55 out of 58 cases (94.8%). Overall positive rate of Al18F-NOTA-FAPI-04 imaging was as high as 18F-FDG imaging (P = 0.625). 18F-FDG imaging detected more lesions in lymph node, spleen, and bone marrow. Al18F-NOTA-FAPI-04 imaging detected more lesions in the lung, muscle, and tendon/ligament. There was no statistical difference of composing ratio of grades of clinical significance between two imaging modalities (χ2 = 2.875, P = 0.238). The superior rate of Al18F-NOTA-FAPI-04 PET/CT imaging was higher than 18F-FDG imaging (P = 0.020). In subgroup of adult-onset Still's disease, 18F-FDG imaging showed better performance than Al18F-NOTA-FAPI-04 imaging. In most of the other subgroup of ARDs, Al18F-NOTA-FAPI-04 PET/CT imaging overperformed 18F-FDG imaging. Both 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging have excellent sensitivity in ARDs. The detection capabilities of two tracers varied according to the involving organs of ARDs. In most of ARDs except adult-onset Still's disease, Al18F-NOTA-FAPI-04 PET/CT imaging overperformed 18F-FDG imaging. Key Points • 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging have excellent sensitivity in diagnosing of ARDs. • 18F-FDG PET/CT imaging detected more lesions in lymph node, spleen, and bone marrow. • 18F-NOTA-FAPI-04 PET/CT imaging detected more lesions in the lung, muscle, and tendon/ligament. • 18F-NOTA-FAPI-04 PET/CT imaging overperformed18F-FDG in most subgroups of ARDs.

A bispecific nanosystem activates endogenous natural killer cells in the bone marrow for haematologic malignancies therapy.

Haematologic malignancies commonly arise from the bone marrow lesion, yet there are currently no effective targeted therapies against tumour cells in this location. Here we constructed a bone-marrow-targeting nanosystem, CSF@E-Hn, which is based on haematopoietic-stem-cell-derived nanovesicles adorned with gripper ligands (aPD-L1 and aNKG2D) and encapsulated with colony-stimulating factor (CSF) for the treatment of haematologic malignancies. CSF@E-Hn targets the bone marrow and, thanks to the gripper ligands, pulls together tumour cells and natural killer cells, activating the latter for specific tumour cell targeting and elimination. The therapeutic efficacy was validated in mice bearing acute myeloid leukaemia and multiple myeloma. The comprehensive assessment of the post-treatment bone marrow microenvironment revealed that the integration of CSF into a bone-marrow-targeted nanosystem promoted haematopoietic stem cell differentiation, boosted memory T cell generation and maintained bone homoeostasis, with long-term prevention of relapse. Our nanosystem represents a promising strategy for the treatment of haematologic malignancies.

Magnetic Resonance Imaging Features and Functional Score in Patients Requiring Total Knee Arthroplasty.

Introduction Knee osteoarthritis (KOA) is a progressive degenerative disease, with an increasing prevalence among the population. The degenerative changes in KOA affect the cartilage, menisci, synovial tissue, and subchondral bone. The treatment for patients in advanced stages of the disease is total knee arthroplasty (TKA). The purpose of this descriptive study is to identify the MRI features in the case of patients with KOA who did not obtain an improvement in symptoms and joint function after the non-surgical treatmentsand who applied for surgical treatment, i.e. TKA. Also, we aimed to identify the correlations between the MRI changes and the functional score of the patients, as well as the inter-variable correlations. Materials and methods The study was conducted in the Department of Orthopedics and Traumatology at the University Emergency Hospital of Bucharest between January 1, 2023, and January 31, 2024. It included 50 patients who required TKA. This study is a prospective, observational, and descriptive analysis focusing on patients scheduled for TKA. Results The patients in the study group who required TKA had a Knee Society Score (KSS) ranging from 35 to 70and a KSS function score between 24 and 60. Among them, 98% had tricompartmental lesions of the articular cartilage, and 100% presented with osteophytes, even when they were not identifiable radiologically. Additionally, 58% of the patients had changes in the infrapatellar fat pad, 66% presented with joint effusion without any traumatic history, and 86% of the patients had partial or complete lesions of the anterior cruciate ligament. Conclusion TheMRI pattern of the patient who requires TKA consists of the presence of articular cartilage lesions in more than two compartments with exposure of the subchondral bone and diameter greater than 1 cm, meniscus lesions (>grade 2), meniscus extrusion (>grade 1), the presence of bone marrow lesions (BMLs) in the medial or lateral compartment of the femur or tibia, hyperintense signal of the infrapatellar fat pad, anterior cruciate ligament (ACL) lesions (>grade 2), and the presence of osteophytes together with the presence of effusion in the suprapatellar bursa. BMLs and changes in the infrapatellar fat pad may lead to the opening of new research perspectives explaining the complex changes in KOA in relation to the inflammatory process and gene expression.

Do Existing MRI Definitions of Knee Osteoarthritis Identify Knees That Will Develop Clinically Significant Disease Over Up To 11 Years of Follow-Up?

In individuals without radiographic knee osteoarthritis (OA), we investigated whether magnetic resonance imaging (MRI)-defined knee OA at baseline was associated with incident radiographic and symptomatic disease during up to 11 years of follow-up. Osteoarthritis Initiative participants without tibiofemoral radiographic knee OA at baseline were assessed for MRI-based tibiofemoral cartilage damage, osteophyte presence, bone marrow lesions, and meniscal damage/extrusion. We defined MRI knee OA using alternative, reported definitions (Def A and Def B). Kellgren-Lawrence (KL) grade, joint space narrowing (JSN), and frequent knee symptoms (Sx) were assessed at baseline, 1-, 2-, 3-, 4-, 6-, 8-, and 10/11-year follow-up visits. Incident tibiofemoral radiographic knee OA (outcome) was defined as (1) KL ≥2, (2) KL ≥2 and JSN, or (3) KL ≥2 and Sx. Adjusted Cox proportional hazards regression models examined associations of baseline MRI-defined knee OA (Def A and Def B) with incident outcomes during up to 11 years of follow-up. Among 1,621 participants (mean age ± SD 58.8 ± 9.0 years, mean body mass index ± SD 27.2 ± 4.5 kg/m2, 59.5% women), 17% had MRI-defined knee OA by Def A and 24% by Def B. Baseline MRI-defined knee OA was associated with incident KL ≥2 (odds ratio 2.94 [95% confidence interval (95% CI) 2.34-3.68] for Def A and 2.44 [95% CI 1.97-3.03] for Def B). However, a substantial proportion of individuals with baseline MRI-defined knee OA did not develop incident KL ≥2 during follow-up (59% for Def A and 64% for Def B). Findings were similar for the other two outcomes. Current MRI definitions of knee OA do not adequately identify knees that will develop radiographic and symptomatic disease.

Effect of arthroscopic partial meniscectomy on structural degeneration of the knee – A 5-year MRI-based follow-up of the placebo-surgery controlled FIDELITY (Finnish Degenerative Meniscus Lesion Study) trial

ObjectiveTo assess the 5-year effects of arthroscopic partial meniscectomy (APM) vs. placebo-surgery on the development of the structural changes of the knee by MRI. DesignThis multicentre, randomized, participant- and outcome-assessor-blinded, placebo-surgery-controlled trial was carried out in Finland. We randomized 146 adults, mean age 52 years (range 35 to 65) to undergo either APM or placebo surgery. The subjects had symptoms of degenerative medial meniscus tear, a tear verified in MRI and arthroscopy, and no advanced osteoarthritis at baseline. We compared the baseline and 5-year follow-up MRIs using MRI Osteoarthritis Knee Score (MOAKS) scoring to derive subregional data on cartilage damage, osteophytes and bone marrow lesions (BMLs). Progression of structural cartilage changes analysed per subregion was the main outcome, that of osteophytes and BMLs secondary outcomes. We analysed the progression with multilevel logistic regression model on subregion level data, adjusted for randomization stratification factors, and using robust standard errors. ResultsSixty-three (90%) subjects in the APM and 73 (96%) in the placebo-surgery group had MRI at both time points. The adjusted odds ratio (APM vs. placebo-surgery) was 1.31 (95% confidence interval 0.81, 1.94) for progression of cartilage damage, 2.86 (1.16, 6.21) for osteophytes, and 1.43 (0.84, 2.43) for BMLs. ConclusionsWe found a slightly greater risk for progression of osteophytes in the APM group compared to the placebo-surgery group at 5 years after surgery. Trial registrationClinicalTrials.gov (NCT01052233 and NCT00549172).

Percutaneous Injection of Calcium Phosphate Bone Substitute into a Chronic Calcaneal Bone Marrow Lesion Associated with a Fragility/Insufficiency Fracture: A Case Report

Pathologic fractures and marrow lesions of bones in the human foot and ankle can occur secondary to a variety of risk factors. The calcaneus is a rearfoot bone that provides support during weightbearing activities and walking. Although low-risk stress injuries to the bones in the foot and ankle are predominantly treated conservatively in low-demand patients, there are situations where surgical intervention is warranted. Surgical treatment options for calcaneal bone marrow lesions (BML) secondary to stress fractures are dearth with limited evidence supporting the use of the subchondroplasty (SCP) technique. This case report discusses surgical treatment with SCP of a chronic calcaneal BML sustained secondary to a insufficiency/fragility fracture.

Progression of Bone Marrow Lesions and the Development of Knee Osteoarthritis: Osteoarthritis Initiative Data.

Background Bone marrow lesions (BMLs) are a known risk factor for incident knee osteoarthritis (OA), and deep learning (DL) methods can assist in automated segmentation and risk prediction. Purpose To develop and validate a DL model for quantifying tibiofemoral BML volume on MRI scans in knees without radiographic OA and to assess the association between longitudinal BML changes and incident knee OA. Materials and Methods This retrospective study included knee MRI scans from the Osteoarthritis Initiative prospective cohort (February 2004-October 2015). The DL model, developed between August and October 2023, segmented the tibiofemoral joint into 10 subregions and measured BML volume in each subregion. Baseline and 4-year follow-up MRI scans were analyzed. Knees without OA at baseline were categorized into three groups based on 4-year BML volume changes: BML-free, BML regression, and BML progression. The risk of developing radiographic and symptomatic OA over 9 years was compared among these groups. Results Included were 3869 non-OA knees in 2430 participants (mean age, 59.5 years ± 9.0 [SD]; female-to-male ratio, 1.3:1). At 4-year follow-up, 2216 knees remained BML-free, 1106 showed an increase in BML volume, and 547 showed a decrease in BML volume. BML progression was associated with a higher risk of developing radiographic knee OA compared with remaining BML-free (hazard ratio [HR] = 3.0; P < .001) or BML regression (HR = 2.0; P < .001). Knees with BML progression also had a higher risk of developing symptomatic OA compared with BML-free knees (HR = 1.3; P < .001). Larger volume changes in BML progression were associated with a higher risk of developing both radiographic OA (HR = 2.0; P < .001) and symptomatic OA (HR = 1.7; P < .001). In almost all subchondral plates, especially the medial femur and tibia, BML progression was associated with a higher risk of developing both radiographic and symptomatic OA compared with remaining BML-free. Conclusion Knees with BML progression, according to subregion and extent of volume changes, were associated with an increased risk of OA compared with BML-free knees and knees with BML regression, highlighting the potential utility of monitoring BML volume changes in evaluating interventions to prevent OA development. ClinicalTrials.gov Identifier: NCT00080171 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Said and Sakly in this issue.

Insights on Progressive Bone Marrow Lesions with AI: An Imaging Biomarker for Knee Osteoarthritis Prediction.

Insights on Progressive Bone Marrow Lesions with AI: An Imaging Biomarker for Knee Osteoarthritis Prediction.

A case of posttransplant isolated extramedullary relapse of acute lymphoblastic leukemia achieving durable treatment-free remission with blinatumomab and donor lymphocyte infusion.

Acute lymphoblastic leukemia (ALL) relapsed after allogeneic hematopoietic cell transplantation (allo-HCT) has a catastrophic prognosis. Blinatumomab, a CD3/CD19-directed bispecific T cell engager, is reportedly effective for advanced B-cell ALL (B-ALL), even after allo-HCT. However, the efficacy of blinatumomab in extramedullary relapse (EMR) is controversial. Donor lymphocyte infusion (DLI) is another immunological treatment worth considering for ALL relapsed after allo-HCT. We report the case of a 56-year-old woman with B-ALL. Allo-HCT was performed during the second complete remission (CR). Thirteen months after allo-HCT, isolated EMR (iEMR) of B-ALL developed without bone marrow lesions. A third CR was achieved with 2 cycles of blinatumomab. An additional four cycles each of blinatumomab and DLI were then administered. The patient did not develop graft-versus-host disease and has confirmed 2-year treatment-free remission without a second allo-HCT. Therefore, blinatumomab was considered an effective salvage therapy for iEMR of B-ALL after allo-HCT, because iEMR could have a lower tumor burden than that seen in systemic relapse, and low tumor burden was a prognostic factor for response to blinatumomab. Furthermore, immunological consolidation therapies could only provoke graft-versus-leukemia effects if the imbalanced effector/target ratio was restored and the tumor burden was lowered through immunosurveillance.

Comparison of MRI Osteoarthritis Knee Score with Clinico-Radiological Grading

Abstract Background Knee joint osteoarthritis (OA) is among the most prevalent degenerative diseases of the joints in the body. Various scoring system exists for grading OA, such as (1) magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS), (2) clinical grading by Western Ontario and McMaster Universities Arthritis Index (WOMAC), and (3) X-ray grading of the Kellgren–Lawrence grading system (K-L). Objectives To study MRI findings and MOAKS scoring of knee OA and correlation with WOMAC and K-L scoring. Setting and Design Cross-sectional study in hospital population. Methods and Material A total 40 knee OA cases underwent an MRI of the knee. MOAKS scoring was done and compared with K-L grading and WOMAC scores. Statistical Analysis Collected data were compiled systematically and interpreted using IBM SPSS statistics software 25.0. A p-value of less than 0.05 was considered significant. Results The mean total WOMAC score was 9. K-L grade 2 was the most prevalent X-ray grade. Bone marrow lesion (BML) and cartilage loss in MOAKS score were greater in the medial femorotibial region. A moderate positive correlation was noted between the WOMAC score and K-L grade; full-thickness articular cartilage loss score at the medial femorotibial joint (MFTJ) and WOMAC score; partial-thickness articular cartilage loss score at lateral femorotibial joint (LFTJ) and WOMAC total pain score. No correlation was found between BML and pain severity score. Conclusion Higher WOMAC scores were associated with higher grades of K-L scoring and score of cartilage loss (partial and full thickness) of the MOAKS scoring system. The rest of the features of the MOAKS score (BML score, osteophyte, and synovitis) had no significant association with pain severity and K-L grading.

Ligamentum teres lesions are associated with compositional and structural hip cartilage degenerative change: region-specific cartilage degeneration.

To investigate the association between magnetic resonance imaging (MRI)-based ligamentum teres lesions (LTL) and structural hip degeneration. Bilateral 3-T hip MRIs of participants (n = 93 [36 men]; mean age ( ± SD) 51 years ± 15.4) recruited from the community and the orthopedic clinic of a single medical center were included. Clinical and imaging data acquired included hip disability and osteoarthritis outcome scores, semi-quantitative scoring of hip osteoarthritis on MRI (SHOMRI) scores on fluid-sensitive sequences, and cartilage T1ρ/T2 compositional sequences. An MRI-based LTL scoring system, incorporating continuity, thickening, and signal intensity, ranging from 0 (normal) to 4 (complete tear) was constructed. Hip morphological features associated with LTL, based on functional or anatomical relationships to LT, were defined. Relationships between MRI-LT scores and SHOMRI, global/regional cartilage T1ρ/T2, and proposed morphological abnormalities and LTL were explored by mixed effects linear and logistic regression models. In 82 (46.1%) hips, no pain was documented; 118 (63.4%) and 68 (36.6%) hips were graded as KL-grade ≤ 1 and ≥ 2, respectively. Compared to MRI-LT score = 0 (normal), score = 4 (complete tear) revealed significantly worse subchondral bony degenerative changes for bone marrow lesions (SHOMRI-BML) and subchondral cysts (SHOMRI-sc) (p < 0.001, p = 0.015, respectively). Global acetabular T1ρ, femoral T2 were significantly increased for abnormal MRI-LT scores (p-range = 0.005-0.032). Regional analyses revealed significantly increased T1ρ/T2 in central acetabular/increased T2 in off-central femoral regions (p-range = 0.005-0.046). Pulvinar effusion-synovitis, shallow fovea, and foveal osteophytes were significantly associated with abnormal LT MRI findings (p-range = < 0.001-0.044). MRI abnormalities of LT are associated with worse SHOMRI-sc/BML scores, indicative of hip osteoarthritis and higher T1ρ and T2 that differ by region. Pulvinar effusion-synovitis and changes in femoral head morphology are associated with LTL. Abnormal ligamentum teres findings identified via MRI are associated with structural degenerative changes of the hip joint and alterations in acetabular and femoral cartilage compositions show spatial differences in relation to LTL. The clinical significance of common ligamentum teres lesions (LTL) on MRI is not well understood. LTL identified by an MRI-based scoring system is associated with worse biomarkers, indicating more advanced degenerative hip changes. Effusion-synovitis signal at pulvinar, shallow fovea capitis, and foveal osteophytes are associated with LTL on imaging.

The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. Purpose: To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. Results: Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, –9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. Conclusion: In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.

Subchondroplasty® (SCP) Provides Resolution of Symptoms and Functional Improvements in Mild-to-Moderate Knee Osteoarthritis with Persistent Bone Marrow Lesions: 12-Month Follow-Up Results from a Multicentric Open-Label Prospective Clinical Trial.

Introduction. Bone marrow lesions (BMLs) are MRI-visible subchondral bone alterations, highly correlated with symptoms in the knee. Subchondroplasty (SCP) is able to fill the subchondral defects associated with BMLs using an injectable bone substitute material. The aim of the present study is to evaluate the 12-month outcomes of the SCP in the treatment of symptoms of mild-to-moderate knee osteoarthritis (OA) patients with persistent BMLs of the knee. Materials and Methods. Subjects affected by BMLs of the femoral condyle or tibial plateau that were present for >3 months and not responsive to conservative treatments were enrolled in this prospective multicenter trial. All the patients underwent SCP. Follow-up was conducted at 1, 3, 6 and 12 months. All subjects completed Numerical Rating Scale (NRS) for pain, Knee Injury and Osteoarthritis Outcome (KOOS) score, Euro Quality of life-5 dimensions (EQ-5D) score, and a subject global satisfaction scale. Demographic information of the patients was also collected. Results. A total of 79 patients completed the 12-month follow-up. Statistically significant improvements on all clinical scales were registered from baseline to the 12-month follow-up. No severe adverse events were reported. Four patients were considered failed. A 12-month subgroup analysis was performed to evaluate the possible correlation between all the KOOS subscales and age, gender, number of BMLs, location of BMLs, and Kellgren-Lawrence grade: no statistically significant associations were observed. Conclusion. SCP is a safe and effective procedure for the treatment of symptoms related to persisting BMLs in mild-to-moderate osteoarthritic knees, with a low failure rate up to 12 months' evaluation.

Increased nerve growth factor expression and osteoclast density are associated with subchondral bone marrow lesions in osteoarthritic knees

ObjectivesSubchondral bone marrow lesions (BMLs) detected on magnetic resonance imaging in knee osteoarthritis (OA) are associated with knee pain, though the mechanisms remain unknown. Increased nerve growth factor (NGF) expression and osteoclast density in subchondral bone appear to be the key features associated with bone pain in knee OA. Therefore, we aimed to identify associations among NGF, osteoclasts, and BMLs in knee OA. MethodsTwenty tibial plateaus were obtained from patients undergoing total knee arthroplasty for medial knee OA with BMLs at the medial tibial plateau (MTP). Osteochondral tissue samples from the weight-bearing part of the MTP, with and without BML, and from the weight-bearing part of the lateral tibial plateau (LTP), without BML, were collected. NGF expression and density of osteoclasts were compared among the three osteochondral tissue types. ResultsMTP bone with BMLs exhibited significantly higher NGF expression in bone marrow space and osteochondral channel, and higher osteoclast density than MTP bone without BML and LTP bone. The mean differences in NGF-positive area in the bone marrow space and the percentage of NGF-positive channels between MTP bones with and without BML were 9.0% (95% confidence interval [CI]: 5.9–12.1%) and 23.1% (95% CI: 11.3–35.0%), respectively. The difference in osteoclast density between MTP bones with and without BML was 0.6 osteoclasts per mm (95% CI: 0.3–0.9 osteoclasts per mm). ConclusionsIncreased NGF expression and osteoclast density are associated with subchondral BMLs in knee OA, contribute to understanding the mechanisms underlying BML-related bone pain in knee OA.