Bone Marrow Lesions In Osteoarthritis Research Articles

Bone marrow lesions in osteoarthritis: From basic science to clinical implications

Osteoarthritis (OA) is the most prevalent musculoskeletal disease characterized by multiple joint structure damages, including articular cartilage, subchondral bone and synovium, resulting in disability and economic burden. Bone marrow lesions (BMLs) are common and important magnetic resonance imaging (MRI) features in OA patients. Basic and clinical research on subchondral BMLs in the pathogenesis of OA has been a hotspot. New evidence shows that subchondral bone degeneration, including BML and angiogenesis, occurs not only at or after cartilage degeneration, but even earlier than cartilage degeneration. Although BMLs are recognized as important biomarkers for OA, their exact roles in the pathogenesis of OA are still unclear, and disputes about the clinical impact and treatment of BMLs remain. This review summarizes the current basic and clinical research progress of BMLs. We particularly focus on molecular pathways, cellular abnormalities and microenvironmental changes of subchondral bone that contributed to the formation of BMLs, and emphasize the crosstalk between subchondral bone and cartilage in OA development. Finally, potential therapeutic strategies targeting BMLs in OA are discussed, which provides novel strategies for OA treatment.

Safety and early results of Subchondroplasty® for the treatment of bone marrow lesions in osteoarthritis: a systematic review

Subchondroplasty® is a novel minimally invasive procedure for painful subchondral bone marrow lesions (BMLs). The aim of this systematic review was to characterize the clinical outcomes of the Subchondroplasty® procedure, a novel minimally invasive procedure for the treatment of BMLs. The hypothesis tested was that patients experience improvements in pain and functional outcomes following the Subchondroplasty® procedure. MEDLINE, Embase, Web of Science, and Clinicaltrials.gov were searched from database inception to search date (June 10, 2020) for all clinical studies which discussed Subchondroplasty®. Two reviewers independently screened 45 unique results and 17 studies were included in the final analysis. Data were collected regarding patient demographics, indications, pain, functional scores, conversion to TKA, and complications of the procedure. All but one study were level IV evidence; the mean MINORS score was 9 ± 2. There were 756 patients included, 45.1% were female, and the mean age was 54years (range 20-85). Thirteen studies investigated the effect Subchondroplasty® to the knee, while four studied the impact on the foot and ankle. Median length of follow-up was 12months. The most common indication for Subchondroplasty® was joint pain with corresponding BML. Major contraindications to Subchondroplasty® included severe OA, joint instability, and malalignment. Mean pain score on visual analogue scale (VAS) prior to Subchondroplasty® was 7.8 ± 0.6, but decreased to 3.4 ± 0.7 postoperatively. All studies investigating functional scores reported improvement following Subchondroplasty® (IKDC 31.7 ± 1.9-54.0 ± 4.2 and KOOS 38.1 ± 0.6-70.0 ± 4.1). There were consistently high levels of patient satisfaction; 87 ± 8% of patients would be willing to undergo the procedure again. Seven cases of complications were reported, most seriously osteomyelitis and avascular necrosis. Conversion to knee arthroplasty ranged from 12.5 to 30% with length of follow-up ranging from 10months to 7years. Existing low-quality studies show Subchondroplasty® to benefit patients with BMLs through reduction in pain and improvement in function, along with a high degree of satisfaction following the procedure. The low short-to-medium term conversion rate to arthroplasty suggests that Subchondroplasty® may play a role in delaying more invasive and expensive procedures in patients with BMLs. Subchondroplasty® is a novel procedure that has promising initial findings, but requires further high-quality, comparative studies with long-term follow-up to better understand the outcomes of the procedure and impact clinical practice recommendations. Systematic Review of Level III and IV Studies, Level IV.

Altered protein levels in bone marrow lesions of hip osteoarthritis: Analysis by proteomics and multiplex immunoassays

To assess tissue level changes of proteome and cytokine profiles of subchondral bone in hip osteoarthritis (OA) affected by bone marrow lesions (BMLs). We compared significant protein level differences in osteoarthritic bone with BMLs to control bone without bone marrow lesions. Subchondral bone biopsies were taken from femoral heads of end-stage osteoarthritis patients with (BML, n=21) and without (CON, n=9) BMLs. Proteins were extracted through a standardized Trizol protocol and used in the subsequent analyses. Angiogenesis and bone markers were assessed using multiplex immunoassays (Luminex). Liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed to detect significant differences in proteome and peptide profiles between BML and CON. Multiplex immunoassays revealed increased tissue contents of vascular endothelial growth factors (VEGF-A/C/D), endothelin-1, angiopoietin-2 and interleukin-6 (IL-6) in bone with BMLs compared to control bone, whereas osteoprotegerin levels were reduced. Mass spectrometry demonstrated pronounced increase in the levels of hemoglobin (73-fold), serum albumin (30-fold), alpha-1-antitrypsin (9-fold), apolipoprotein A1 (4.7-fold), pre-laminin-A/C (3.7-fold) and collagen-alpha1-XII (3-fold) in BMLs, while aggrecan core protein (ACAN) and hyaluronan and proteoglycan link protein 1 (HAPL1) decreased 37- and 29-fold respectively. Reduced osteoprotegerin, ACAN and HAPL1 are consistent with osteoclastic activation and high remodeling activity in BMLs. The pronounced increase in angiogenesis markers, hemoglobin and serum albumin support the presence of increased vascularity in subchondral bone affected by BMLs in OA. VEGFs and IL-6 are known nociceptive modulators, and increased levels are in keeping with pain being a clinical feature frequently associated with BMLs.

OMERACT Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) Assessment in Longitudinal Study.

To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA). HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts. HIMRISS reliability was excellent for BML status (ICC 0.83-0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76-0.81) and moderate in acetabulum (0.42-0.56). HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.

Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb.

ObjectivesLittle is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA.MethodsPatients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty.ResultsAll trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean sd 0.2 (0.1) versus 0.01 (0.01) µm3/µm2/day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm3/µm2/day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia.ConclusionBone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI.Cite this article: M. Shabestari, N. J. Kise, M. A. Landin, S. Sesseng, J. C. Hellund, J. E. Reseland, E. F. Eriksen, I. K. Haugen. Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone Joint Res 2018;7:406–413. DOI: 10.1302/2046-3758.76.BJR-2017-0083.R3.

Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation

ObjectiveBone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated...

SAT0454 Comparative Validation of an Electronic Overlay Enhanced Target-Lesion Based Methodology with the Volumetric Based MRI Osteoarthritis Knee Score for Scoring Bone Marrow Lesions in Osteoarthritis of the Knee

BackgroundThe primary MRI scoring method for assessment of bone marrow lesions (BML) in the knee in OA, MOAKS, relies on a subdivision of the knee into15 subregions and then estimation...

Osteoarthritis bone marrow lesions at the knee and large artery characteristics

There is evidence to suggest vascular involvement in the initiation and progression of osteoarthritis (OA). The relationship between large artery characteristics and pathogenesis of OA has not been investigated and was the aim of this study. Large artery characteristics (i.e., aortic stiffness, brachial and central blood pressure (BP) variables) and bone marrow lesions (BMLs; measured by magnetic resonance imaging as a surrogate index of OA) were recorded in 208 participants (aged 63 ± 7 years; mean ± SD) with symptomatic knee OA. Relationships between large artery characteristics and BML were assessed by multiple regression adjusting for age, sex and body mass index. There was a high prevalence of BML presence in the study population (70%), but no significant difference between participants with and without BML for all large artery and BP variables (P > 0.05 all). Furthermore, there were no significant relationships between BML size and aortic stiffness (r = -0.033, P = 0.71), central pulse pressure (r = 0.028, P = 0.74), augmentation index (r = 0.125, P = 0.14), brachial pulse pressure (r = 0.005, P = 0.95) or brachial systolic BP (r = -0.066, P = 0.44). When participants were stratified according to high or low aortic stiffness, there was no significant difference between groups regarding the proportion of those with a BML (64% vs. 70% respectively; P = 0.69). Variables indicative of large artery characteristics are not significantly correlated with BML size or presence in people with symptomatic knee OA. Thus, large artery characteristics may not have a causative influence in the development of OA, but this needs to be confirmed in prospective studies.

Are biomechanical factors, meniscal pathology, and physical activity risk factors for bone marrow lesions at the knee? A systematic review

ObjectiveTo systematically review the literature to determine whether biomechanical factors, meniscal pathology, and physical activity are risk factors for bone marrow lesions (BMLs) at the knee identified from magnetic resonance imaging in pre-osteoarthritis and osteoarthritis populations. MethodsElectronic searches of MEDLINE and EMBASE were performed from January 1, 1996 to October 31, 2012 using the keywords of bone marrow lesion(s), bone marrow (o)edema, osteoarthritis, and knee. Studies examining biomechanical factors, meniscal pathology, or physical activity in relation to the presence, incidence, or change in BMLs at the knee were included. Two independent reviewers extracted the data and assessed the methodological quality of selected studies. Due to the heterogeneity of the studies, we performed a best evidence synthesis. ResultsFifteen studies were included in this review, of which 9 were considered high quality. The study populations were heterogeneous in terms of the symptoms and radiographic knee osteoarthritis. There was strong evidence for relationships of mechanical knee alignment and meniscal pathology with BMLs in osteoarthritis populations. There was a paucity of evidence for a relationship between physical activity and BMLs. ConclusionDespite the heterogeneity of included studies, these data suggest that mechanical knee alignment and meniscal pathology are risk factors for BMLs in knee osteoarthritis. It suggests that BMLs in individuals with osteoarthritis are more susceptible to mechanical knee alignment. Given the role of BMLs in the pathogenesis of knee osteoarthritis, identifying strategies to modify these risk factors will be important in slowing the progression and reducing the burden of knee osteoarthritis.

Assessment of perfusion in osteoarthritis induced bone marrow lesions using dynamic contrast enhanced magnetic resonance imaging

Assessment of perfusion in osteoarthritis induced bone marrow lesions using dynamic contrast enhanced magnetic resonance imaging

Cartilage loss, measured with mri, predicts knee replacement - data from the osteoarthritis initiative

Cartilage loss, measured with mri, predicts knee replacement - data from the osteoarthritis initiative

Akuter, traumatischer versus chronischer Knorpelschaden unter gutachterlichen Gesichtspunkten

Have chondral lesions been found in the course of an articular injury? Are these lesions of traumatic or degenerative origin? Is it possible to differentiate traumatic from pre-existing pathology with the help of history, clinical findings and imaging features? The answers to these questions are of paramount importance in the setting of legal expert assessment. The diagnosis of an acute traumatic chondral injury is based on arthroscopic and/or MRI findings. MRI is the diagnostic method of choice in a suspected isolated chondral injury. The method yields high accuracy in detecting chondral and osteochondral lesions. The MRI finding of a concomitant subchondral bone contusion ("bone bruise") adjacent to a cartilage lesion helps in the diagnosis of acute chondral lesions. Traumatic bone marrow alterations regress in most cases over the course of 6 months. For this reason the initial MRI should be performed within 1 to 6 weeks after trauma. A follow-up study should be undertaken not prior to 3 months after injury. Osteoarthritic cartilage lesions show a distinct regional pattern on MRI usually affecting the weight-bearing regions. In advanced stages, regularly concomitant osseous reactions such as osteophytes, subchondral sclerosis and bone attrition are observed. Subchondral bone marrow lesions in osteoarthritis show a tendency to progress. The direct inspection and probing of the joint during arthroscopy allows for a detailed assessment of the chondral surface and the diagnosis of possible cartilage softening. An arthroscopic differentiation between acute traumatic chondral lesions and chronic cartilage alterations is possible in most cases within the first 6 to 12 weeks after injury.