A review of bone marrow lesions in the arthritic knee and description of a technique for treatment
01 Sep 2021-Vol. 1, Iss: 3, pp 100021
TL;DR: The use of novel biologic techniques to treat BMLs in the knee, such as PRP and Bone Marrow Cells, has yielded promising clinical outcomes and a need for high-quality RCTs studies and systematic reviews in the future to enhance further treatment strategy.
Abstract: Introduction Subchondral bone pathology includes a wide range of pathologies, such as osteoarthritis, spontaneous insufficiency fractures, osteonecrosis, transient bone marrow lesions syndromes, and trauma. They show typical magnetic resonance imaging (MRI) findings termed bone marrow lesions (BMLs). However, the etiology and evolution of BMLs in multiple conditions remains unclear. There is still no gold standard treatment protocol in treating BMLs in the knee, and a variety of treatment modalities have been tested in the hope that they might reduce pain and stop disease progression. Objectives To review the treatment options for BMLs of the knee. Methods A literature review was performed that included searches of PubMed, Cochrane, and Medline databases using the following keywords: Bone marrow lesions, sub chondroplasty, bone marrow concentrate, platelet-rich plasma (PRP), subchondral bone augmentation. Results The use of novel biologic techniques to treat BMLs in the knee, such as PRP and Bone Marrow Cells, has yielded promising clinical outcomes. Conclusions Future research of BMLs will be mandatory to address the different pathologies better and determining appropriate treatment strategies. There is still a need for high-quality RCTs studies and systematic reviews in the future to enhance further treatment strategy in preventing or treating BMLs of the knee.
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TL;DR: In this article , mesenchymal stem cells (MSCs) were used to treat bone marrow lesion in patients with knee osteoarthritis and avascular necrosis.
Abstract: Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.
2 citations
TL;DR: Preliminary results confirm that biological subchondral bone augmentation by Osteo Core Plasty technique is a safe and effective minimally invasive treatment option for symptomatic BMLs in the knee at 1-year follow-up.
Abstract: Bone Marrow Lesions (BMLs) are typical findings in magnetic resonance imaging (MRI) present in different pathologies, such as spontaneous insufficiency fractures, osteonecrosis, transient BML syndromes, osteoarthritis, and trauma. The etiology and evolution of BMLs in multiple conditions remain unclear. There is still no gold standard protocol for the treatment of symptomatic BMLs in the knee. The biologic augmentation by Osteo Core Plasty is a new treatment modality showing promising results reducing pain with the aim to stop the progression of the disease. The purpose of this prospective study is to report the clinical outcomes and safety of Osteo Core Plasty for the treatment of symptomatic BMLs in the knee. Fifteen patients with symptomatic BMLs of the knee treated with the Osteo Core Plasty technique were included and followed prospectively for a minimum of 12 months. Each patient was evaluated before the surgery and respectively at 6 and 12 months using the Tegner Score, Marx Score, the International Knee Documentation Committee (IKDC), the Knee Injury and Osteoarthritis Outcome Score (KOOS) divided in pain, activity daily living (ADL) and Quality of Life (QOL) subscale and the Visual Analogue Scale (VAS) for pain. All clinical scores except Tegner and Marx score showed an overall statistically significant improvement through the entire follow-up (p<0.05) and a significant improvement (p<0.05) between each follow-up period (T0 versus T1; T0 versus T2; T1 versus T2). No complications were reported. These preliminary results confirm that biological subchondral bone augmentation by Osteo Core Plasty technique is a safe and effective minimally invasive treatment option for symptomatic BMLs in the knee at 1-year follow-up. There is still a need for high-quality RCTs studies and systematic reviews in the future to enhance further treatment strategies in preventing or treating BMLs of the knee.
2 citations
01 Jan 2015
TL;DR: The identification, isolation, and characterization of these human blood-vessel-derived stem cells (hBVSCs) are discussed and the current status of regenerative applications of hBV SC subsets is summarized.
Abstract: Mesenchymal stem/stromal cells (MSCs) represent a promising adult progenitor cell source for tissue repair and regeneration. Their mysterious identity in situ has gradually been unveiled by the accumulating evidence indicating an association between adult multipotent stem/progenitor cells and vascular/perivascular niches. Using immunohistochemistry and fluorescence-activated cell sorting, we and other groups have prospectively identified and purified subpopulations of multipotent precursor cells associated with the blood vessels within multiple human organs. The three precursor subsets, myogenic endothelial cells (MECs), pericytes (PCs), and adventitial cells (ACs), are located, respectively, in the three structural tiers of typical blood vessels: intima, media, and adventitia. MECs, PCs, and ACs have been extensively characterized in prior studies and are currently under investigation for their therapeutic potentials in preclinical animal models. In this review, we will briefly discuss the identification, isolation, and characterization of these human blood-vessel-derived stem cells (hBVSCs) and summarize the current status of regenerative applications of hBVSC subsets.
2 citations
01 Sep 2021
TL;DR: This issue of the Journal of Joint Preservation and Cartilage Restoration (JCJP), the official journal of the International Cartilage Regeneration & Joint Preservation Society (ICRS), has several outstanding articles from thought leaders in joint preservation from around the globe.
Abstract: As your new Editor-in-Chief, it is my honor to introduce this issue of the Journal of Joint Preservation and Cartilage Restoration (JCJP), the official journal of the International Cartilage Regeneration & Joint Preservation Society (ICRS). As many of our readers already know, this journal is an exciting new endeavor sponsored and supported by ICRS, and made possible through Elsevier. I am excited to work with our entire editorial team on our vision to expand upon the incredible foundation established by inaugural Editor-in-Chief, Dr. Lisa Fortier, and help build the journal’s reputation as a leading publication in joint preservation and cartilage regeneration. Given the open access nature of this journal, the ability for clinicians, researchers, and students to publish in a timely fashion in a peer-reviewed setting is seemingly unlimited. We anticipate that JCJP will have a global impact in the near term. The mission of JCJP aligns perfectly with the mission of ICRS – to advance science and education for the prevention and treatment of cartilage disease worldwide. In this issue, we have several outstanding articles from thought leaders in joint preservation from around the globe. First, we have an article by ICRS past-president Professor Alberto Gobbi and colleagues entitled “A Review of Bone Marrow Lesions in the Arthritic Knee and Description of a Technique for Treatment . ”1 In this article, the authors discuss the etiology and types of bone marrow lesions, as well as the biology and biomechanics of these lesions along with relevant anatomy. Treatment options for these difficult entities are also reviewed, including a description of the technique and benefits of a novel minimally invasive procedure to induce bone remodeling referred to as Osteo-Core-Plasty. Next, we have an article from the lab of ICRS past-president Dr. Lisa Fortier (and prior editor-in-chief) entitled “Bone marrow concentrate mesenchymal stromal cells do not correlate with nucleated cell count or colony forming units. ”2 Point-ofcare bone marrow aspirate concentrate has become a more frequently used biologic treatment for cartilage repair and osteoarthritis given its bioactive components. Measuring the concentration of mesenchymal stromal cells in bone marrow aspirate concentrate is difficult, yet critical for determining their specific influence on healing. This article describes a study in which the authors analyzed two proposed techniques, nucleated cell count and colony forming units, that more simply quantify MSC concentration as compared to advanced methods. Next, the role of adipose is discussed in an article led by Hannah Bradsell, entitled “The Essential Roles of Human Adipose Tissue: Metabolic, Thermoregulatory, Cellular, and Paracrine Effects . ”3 In this article, the authors describe the various roles of human adipose tissue, including the important functions of adipose-derived mesenchymal stromal cells, which contain several biologic properties that exhibit paracrine and immunomodulatory functions, as well as the ability to differentiate into multiple lineages, including chondrogenic and osteogenic cell lines. This article discusses the anatomy, physiology, and various roles and properties of human adipose tissue to better understand this tissue before considering it as a cellular source. The next article in this issue is led by Dr. Nguyen Huu Chien and colleagues, entitled “The Need for a Standardized Whole Leg Radiograph Guideline: The Effects of Knee Flexion, Leg Rotation, and X-ray Beam Height. ”4 There is a high risk of developing knee osteoarthritis in patients with lower limb malalignment, and accurate alignment measurements are crucial when patients are indicated for total knee arthroplasty or osteotomy. This article analyzes the effects of various factors on the accuracy of Hip-Knee-Ankle-Angle measurements and discusses guidelines for setup and patient positioning to obtain accurate and reproducible whole leg radiographs that minimize HKA measurement errors. Next, the article “How to Salvage the Delivery of a Wrong-Sided Meniscal Allograft: A Rare Case Series ”5 authored by Dr. Jack Farr is presented. While rare, receiving a wrong-sided meniscus allograft during a meniscal transplant procedure is possible. While continuing with the procedure is dependent on many factors, this article describes a guide on how to address this problem as well as the surgical technique
TL;DR: It is demonstrated that the commonly used ROC curve is not sufficiently informative when evaluating the performance of deep learning models in the imbalanced data in OA studies.
Abstract: Objective: To compare the evaluation metrics for deep learning methods in the imbalanced imaging data in osteoarthritis (OA) studies. Method: We first divided MOAKS (MRI Osteoarthritis Knee Score) grades into the presence (MOAKS > 0) and absence (MOAKS = 0) categories. Second, a deep-learning model was trained to the sagittal intermediate-weighted (IW) fat-suppressed (FS) knee MRI images with MOAKS readings from the Osteoarthritis Initiative (OAI) study to predict the presence of bone marrow lesions (BMLs). After the deep learning models were trained, we obtained probabilities of the presence of BMLs from MRI images at the sub-region (15 sub-regions), compartment, and whole-knee levels. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) of the deep learning model in the testing data with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the performance of models. Results: We have demonstrated that the commonly used ROC curve is not sufficiently informative when evaluating the performance of deep learning models in the imbalanced data in OA studies. Conclusion: The class ratios coupled with results of ROC, PR, and Matthews correlation coefficient (MCC) should be reported in OA studies.
References
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TL;DR: 3-dimensional knee joint kinematics in anterior cruciate ligament injury situations is described using a model-based image-matching technique and results suggest that valgus loading is a contributing factor in the anterior cruiser injury mechanism and that internal tibial rotation is coupled with valgUS motion.
Abstract: Background: The mechanism for noncontact anterior cruciate ligament injury is still a matter of controversy. Video analysis of injury tapes is the only method available to extract biomechanical information from actual anterior cruciate ligament injury cases. Purpose: This article describes 3-dimensional knee joint kinematics in anterior cruciate ligament injury situations using a modelbased image-matching technique. Study Design: Case series; Level of evidence, 4. Methods: Ten anterior cruciate ligament injury video sequences from women’s handball and basketball were analyzed using the model-based image-matching method. Results: The mean knee flexion angle among the 10 cases was 23 (range, 11-30) at initial contact (IC) and had increased by 24 (95% confidence interval [CI], 19-29) within the following 40 milliseconds. The mean valgus angle was neutral (range, 22 to 3) at IC, but had increased by 12 (95% CI, 10-13) 40 milliseconds later. The knee was externally rotated 5 (range, 25 to 12 )a t IC, but rotated internally by 8 (95% CI, 2-14) during the first 40 milliseconds, followed by external rotation of 17 (95% CI, 1322). The mean peak vertical ground-reaction force was 3.2 times body weight (95% CI, 2.7-3.7), and occurred at 40 milliseconds after IC (range, 0-83). Conclusion: Based on when the sudden changes in joint angular motion and the peak vertical ground-reaction force occurred, it is likely that the anterior cruciate ligament injury occurred approximately 40 milliseconds after IC. The kinematic patterns were surprisingly consistent among the 10 cases. All players had immediate valgus motion within 40 milliseconds after IC. Moreover, the tibia rotated internally during the first 40 milliseconds and then external rotation was observed, possibly after the anterior cruciate ligament had torn. These results suggest that valgus loading is a contributing factor in the anterior cruciate ligament injury mechanism and that internal tibial rotation is coupled with valgus motion. Prevention programs should focus on acquiring a good cutting and landing technique with knee flexion and without valgus loading of the knee.
763 citations
TL;DR: A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.
Abstract: Osteoarthritis (OA) is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.
702 citations
TL;DR: Basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage, are summarized and a hypothetical model for the pathogenesis of OA is proposed.
Abstract: Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.
551 citations
TL;DR: A profound understanding of the basic anatomic aspects of this particular site, together with the pathophysiology of diseases affecting the subchondral bone is the key to develop targeted and effective therapeutic strategies to treat osteochondral defects.
Abstract: In the past decades, considerable efforts have been made to propose experimental and clinical treatments for articular cartilage defects. Yet, the problem of cartilage defects extending deep in the underlying subchondral bone has not received adequate attention. A profound understanding of the basic anatomic aspects of this particular site, together with the pathophysiology of diseases affecting the subchondral bone is the key to develop targeted and effective therapeutic strategies to treat osteochondral defects. The subchondral bone consists of the subchondral bone plate and the subarticular spongiosa. It is separated by the cement line from the calcified zone of the articular cartilage. A variable anatomy is characteristic for the subchondral region, reflected in differences in thickness, density, and composition of the subchondral bone plate, contour of the tidemark and cement line, and the number and types of channels penetrating into the calcified cartilage. This review aims at providing insights into the anatomy, morphology, and pathology of the subchondral bone. Individual diseases affecting the subchondral bone, such as traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis are also discussed. A better knowledge of the basic science of the subchondral region, together with additional investigations in animal models and patients may translate into improved therapies for articular cartilage defects that arise from or extend into the subchondral bone.
487 citations
TL;DR: Development of knee pain is associated with an increase in BMLs as revealed on MRI, and multiple logistic regression was used to assess whether an increased BML score is predictive of the development of kneePain.
Abstract: Objective
Results of cross-sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether enlarging BMLs are associated with new knee pain.
Methods
Subjects ages 50–79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months' followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at followup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee compartments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clinical variables, was used to assess whether an increased BML score is predictive of the development of knee pain.
Results
Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compartment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi-square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5–6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarging BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more common in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83).
Conclusion
Development of knee pain is associated with an increase in BMLs as revealed on MRI.
406 citations