Objectives: The purpose of the present systematic review and meta-analysis is to summarize the current evidence on the role of bisphosphonates in the treatment of knee bone marrow lesions (BMLs), to understand whether they are truly effective in improving symptoms and restoring the subchondral bone status at imaging evaluation. Methods: A literature search was carried out on PubMed, Cochrane, and Google Scholar databases in accordance with the PRISMA guidelines. Potential risk of bias was evaluated using the Cochrane Risk of Bias 2 tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies. Results: A total of 15 studies were included in the present systematic review and meta-analysis. Seven studies were RCTs, two were prospective cohort studies, three were retrospective, and three were case series. Our meta-analysis revealed that bisphosphonates did not significantly improve clinical scores or reduce BML size compared to placebo. Accordingly, the rate of adverse events was also non-significantly higher among bisphosphonate users versus placebo users. Conclusions: The main finding of the present meta-analysis and systematic review is that bisphosphonates show neither significant benefits nor significant adverse events when compared to placebo in the treatment of BMLs of the knee. Level of Evidence: Level IV systematic review of level II-III-IV studies. Level I meta-analysis of level I studies.

Bone marrow lesion (BML) volume is a potential biomarker of knee osteoarthritis (KOA) as it is associated with cartilage degeneration and pain. However, segmenting and quantifying the BML volume is challenging due to the small size, low contrast, and various positions where the BML may occur. It is also time-consuming to delineate BMLs manually. In this paper, we proposed a fully automatic segmentation method for BMLs without requiring human intervention. The model takes intermediate weighted fat-suppressed (IWFS) magnetic resonance (MR) images as input, and the output BML masks are evaluated using both regular 2D Dice similarity coefficient (DSC) of the slice-level area metric and 3D DSC of the subject-level volume metric. On a dataset with 300 subjects, each subject has a sequence of 36 IWFS MR images approximately. We randomly separated the dataset into training, validation, and testing sets with a 70%/15%/15% split at the subject level. Since not every subject or image has a BML, we excluded the images without a BML in each subset. The ground truth of the BML was labeled by trained medical staff using a semi-automatic tool. Compared with the ground truth, the proposed segmentation method achieved a Pearson\'s correlation coefficient of 0.98 between the manually measured volumes and automatically segmented volumes, a 2D DSC of 0.68, and a 3D DSC of 0.60 on the testing set. Although the DSC result is not high, the high correlation of 0.98 indicates that the automatically measured BML volume is strongly correlated with the manually measured BML volume, which shows the potential to use the proposed method as an automatic measurement tool for the BML biomarker to facilitate the assessment of knee OA progression.

UNASSIGNED: Movement-evoked pain (MEP) is the primary symptom in patients with knee osteoarthritis (KOA).
UNASSIGNED: This study aimed to investigate the contribution of joint structural changes and pain sensitization to the mechanisms of MEP in patients with KOA.
UNASSIGNED: A total of 86 patients were assessed for demographic characteristics, osteoarthritis severity, Whole-Organ Magnetic Resonance Imaging Score-Hoffa synovitis and bone marrow lesions, pressure pain threshold and temporal summation of pain at the knee and forearm, Central Sensitization Inventory-9, and MEP. In measure of MEP, knee pain was scored using a numerical rating scale (NRS, 0-10) before and every minute during a 6-minute walking test (6MWT), and the MEP index was defined as the change in NRS pain score from baseline to the sixth minute of walking.
UNASSIGNED: On average, pain during 6MWT increased by 1.4 ± 1.5 points on the NRS relative to baseline, with 30.2% of patients showing an increase of 2 points or more. The hierarchical linear regression analysis revealed that Hoffa synovitis, pressure pain threshold at the forearm, and temporal summation of pain at the knee were associated with the MEP index.
UNASSIGNED: The findings of this study suggest that both synovitis and neural mechanisms, such as pain sensitization, play a role in the development of MEP in KOA.

OBJECTIVE: To identify bone marrow lesion (BML) trajectories over 4 years and their demographic and structural predictors in middle-aged and older adults with or at increased risk of knee osteoarthritis (OA).
METHODS: A total of 614 participants (mean age 61 years, 62% female) from the Osteoarthritis Initiative cohort (OAI) were included. BMLs in 15 anatomical locations of the knee were measured annually from baseline to 4 years using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) method. BML trajectories were determined using latent class mixed models (LCMMs). Multinomial logistic regression was used to examine baseline characteristics that predicted BML trajectories.
RESULTS: Three distinct BML trajectories were identified: \"Mild-stable BMLs\" (25.9%), \"Moderate-stable BMLs\" (66.4%), and \"Rapid-rise BMLs\" (7.7%). Compared to the \"Mild-stable BMLs\" trajectory, current smokers were more likely to be in the \"Moderate-stable BMLs\" (odds ratio [OR] 2.089, P < 0.001) and \"Rapid-rise\" (OR 2.462, P < 0.001) trajectories. Moreover, female sex and meniscal tears were associated with an increased risk of being in the \"Rapid-rise BMLs\" trajectory (OR 2.023 to 2.504, P < 0.05). Participants who had higher education levels and drank more alcohol were more likely to be in the \"Rapid-rise BMLs\" trajectory (OR 1.624 to 3.178, P < 0.05) and less likely to be in the \"Moderate-stable BMLs\" trajectory (OR 0.668 to 0.674, P < 0.05).
CONCLUSIONS: During the 4-year follow-up, most participants had relatively stable BMLs, few had enlarged BMLs, and no trajectory of decreased BMLs was identified. Sociodemographic factors, lifestyle, and knee structural pathology play roles in predicting distinct BML trajectories.

To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI.
Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0-3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iβ, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined.
Increases in serum CTX-I and urinary CTX-Iβ over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline.
Short-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iβ hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.

UNASSIGNED: We investigated the feasibility of detection and quantification of bone marrow edema (BME) using dual-energy (DE) Cone-Beam CT (CBCT) with a dual-layer flat panel detector (FPD) and three-material decomposition.
UNASSIGNED: A realistic CBCT system simulator was applied to study the impact of detector quantization, scatter, and spectral calibration errors on the accuracy of fat-water-bone decompositions of dual-layer projections. The CBCT system featured 975 mm source-axis distance, 1,362 mm source-detector distance and a 430 × 430 mm2 dual-layer FPD (top layer: 0.20 mm CsI:Tl, bottom layer: 0.55 mm CsI:Tl; a 1 mm Cu filter between the layers to improve spectral separation). Tube settings were 120 kV (+2 mm Al, +0.2 mm Cu) and 10 mAs per exposure. The digital phantom consisted of a 160 mm water cylinder with inserts containing mixtures of water (volume fraction ranging 0.18 to 0.46) - fat (0.5 to 0.7) - Ca (0.04 to 0.12); decreasing fractions of fat indicated increasing degrees of BME. A two-stage three-material DE decomposition was applied to DE CBCT projections: first, projection-domain decomposition (PDD) into fat-aluminum basis, followed by CBCT reconstruction of intermediate base images, followed by image-domain change of basis into fat, water and bone. Sensitivity to scatter was evaluated by i) adjusting source collimation (12 to 400 mm width) and ii) subtracting various fractions of the true scatter from the projections at 400 mm collimation. The impact of spectral calibration was studied by shifting the effective beam energy (± 2 keV) when creating the PDD lookup table. We further simulated a realistic BME imaging framework, where the scatter was estimated using a fast Monte Carlo (MC) simulation from a preliminary decomposition of the object; the object was a realistic wrist phantom with an 0.85 mL BME stimulus in the radius.
UNASSIGNED: The decomposition is sensitive to scatter: approx. <20 mm collimation width or <10% error of scatter correction in a full field-of-view setting is needed to resolve BME. A mismatch in PDD decomposition calibration of ± 1 keV results in ~25% error in fat fraction estimates. In the wrist phantom study with MC scatter corrections, we were able to achieve ~0.79 mL true positive and ~0.06 mL false positive BME detection (compared to 0.85 mL true BME volume).
UNASSIGNED: Detection of BME using DE CBCT with dual-layer FPD is feasible, but requires scatter mitigation, accurate scatter estimation, and robust spectral calibration.

OBJECTIVE: This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA).
METHODS: BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles.
RESULTS: A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The \"has-miR-424-5p/lncRNA PVT1\" was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes.
CONCLUSIONS: IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

Sarcoidosis is a multisystem granulomatous disease of unknown origin. The most frequent localizations are thoracic lymph nodes and/or parenchymal lung disease, nevertheless any other organ may be involved. Musculoskeletal sarcoidosis, previously considered a rare manifestation of the disease, is presently recognized with increasing frequency, due to the development of modern imaging modalities. The classical X-ray sign of bone sarcoidosis is the image of lace in the phalanges of the hands. Most other locations present with atypical radiological images. Therefore, they may mimic metastatic neoplastic disease, especially when they are the first sign of sarcoidosis not previously recognized. On such occasions, none of the imaging methods will give the correct diagnosis, histopathological verification, monitoring of lesions or clinical data in a patient with confirmed sarcoidosis are indicated. The article summarizes the current status of knowledge concerning the recognition and therapy of bone sarcoidosis. In addition, an illustrative case of patient with bone and bone marrow sarcoidosis is presented.

UNASSIGNED: Bone marrow lesions (BMLs) are common subchondral defects revealed by magnetic resonance imaging (MRI) in patients with osteoarthritis, often associated with pain and functional limitation. Subchondroplasty (SCP) is a relatively new technique in which bone substitute material (BSM) is injected inside BML areas to provide structural support to the subchondral bone, preventing its collapse and reducing pain.
UNASSIGNED: The purpose of this study was to characterize changes in pain, functional and radiological outcomes, conversion to knee replacement, and complications after SCP. We hypothesized that ≥70% of patients would achieve a reduction in pain of ≥4 points on a numeric rating scale (NRS) at a 6-month follow-up after SCP.
UNASSIGNED: Case series; Level of evidence, 4.
UNASSIGNED: Patients with symptomatic knee BMLs who underwent SCP were prospectively evaluated preoperatively and at 1, 6, 12, and 24 months postoperatively. Functional outcomes were measured with the NRS for pain, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores. Radiographs and MRI were performed preoperatively and at 6- and 12-month follow-ups to verify edema healing and changes in bone structure.
UNASSIGNED: A total of 50 patients were included in the study. The mean follow-up was 26 months (24-30 months). Compared with preoperative values, the mean NRS score decreased at every follow-up point (P < .0001 for all) and the IKDC, WOMAC, and KSS scores improved significantly at 6- and 12-month follow-ups. At 6 months postoperatively, 27 patients (54%) registered a reduction on the NRS of ≥4 points. Postoperative MRI revealed a hypointense zone surrounded by a hyperintense signal at the injection site. Standard radiography showed osteoarthritis grade worsening in 4 (8%) patients. Knee replacement was performed in 11 patients -in 7 patients due to the worsening or persistence of disabling symptoms and in 4 patients due to the progression of osteoarthritis. The leakage of BSM occurred in 6 patients without any clinical consequences during the study period.
UNASSIGNED: About half of the study patients achieved a reduction in the NRS of 4 points at the 6-month follow-up after SCP.
UNASSIGNED: NCT04905394 (ClinicalTrials.gov identifier).

Imaging plays a pivotal role in osteoarthritis research, particularly in epidemiological and clinical trials of knee osteoarthritis (KOA), with the ultimate goal being the development of an effective drug treatment for future prevention or cessation of disease. Imaging assessment methods can be semi-quantitative, quantitative, or a combination, with quantitative methods usually relying on software to assist. The software generally attempts image segmentation (outlining of relevant structures). New techniques using artificial intelligence (AI) or deep learning (DL) are currently a frequent topic of research. This review article provides an overview of the literature to date, focusing primarily on the current status of quantitative software-based assessment techniques of KOA using magnetic resonance (MR) imaging. We will concentrate on the imaging evaluation of three specific structural imaging biomarkers: bone marrow lesions (BMLs), meniscus, and synovitis consisting of effusion synovitis (ES) and Hoffa\'s synovitis (HS). A brief clinical and imaging background review of osteoarthritis evaluation, particularly relating to these three structural markers, is provided as well as a general summary of the software methods. A summary of the literature with respect to each KOA assessment method will be presented overall as well as with respect to each specific biomarker individually. Novel techniques, as well as future goals and directions using quantitative imaging assessment, will be discussed.