Bone marrow lesions in osteoarthritis: biomarker or treatment target? A narrative review.

Osteoarthritis (OA) is a leading cause of pain, functional impairment, and disability in older adults. However, there are no effective treatments to delay and reverse OA. Magnetic resonance imaging (MRI) can assess structural abnormalities of OA by directly visualizing damage and inflammatory reactions within the tissues and detecting abnormal signals in the subchondral bone marrow region. While some studies have shown that bone marrow lesions (BMLs) are one of the early signs of the development of OA and predict structural and symptomatic progression of OA, others claimed that BMLs are prevalent in the general population and have no role in the progression of OA. In this narrative review, we screened and summarized studies with different designs that evaluated the association of BMLs with joint symptoms and structural abnormalities of OA. We also discussed whether BMLs may serve as an imaging biomarker and a treatment target for OA based on existing clinical trials.

Survival analysis on subchondral bone length for total knee replacement.

OBJECTIVE: Use subchondral bone length (SBL), a new MRI-derived measure that reflects the extent of cartilage loss and bone flattening, to predict the risk of progression to total knee replacement (TKR). METHODS: We employed baseline MRI data from the Osteoarthritis Initiative (OAI), focusing on 760 men and 1214 women with bone marrow lesions (BMLs) and joint space narrowing (JSN) scores, to predict the progression to TKR. To minimize bias from analyzing both knees of a participant, only the knee with a higher Kellgren-Lawrence (KL) grade was considered, given its greater potential need for TKR. We utilized the Kaplan-Meier survival curves and Cox proportional hazards models, incorporating raw and normalized values of SBL, JSN, and BML as predictors. The study included subgroup analyses for different demographics and clinical characteristics, using models for raw and normalized SBL (merged, femoral, tibial), BML (merged, femoral, tibial), and JSN (medial and lateral compartments). Model performance was evaluated using the time-dependent area under the curve (AUC), Brier score, and Concordance index to gauge accuracy, calibration, and discriminatory power. Knee joint and region-level analyses were conducted to determine the effectiveness of SBL, JSN, and BML in predicting TKR risk. RESULTS: The SBL model, incorporating data from both the femur and tibia, demonstrated a predictive capacity for TKR that closely matched the performance of the BML score and the JSN grade. The Concordance index of the SBL model was 0.764, closely mirroring the BML's 0.759 and slightly below JSN's 0.788. The Brier score for the SBL model stood at 0.069, showing comparability with BML's 0.073 and a minor difference from JSN's 0.067. Regarding the AUC, the SBL model achieved 0.803, nearly identical to BML's 0.802 and slightly lower than JSN's 0.827. CONCLUSION: SBL's capacity to predict the risk of progression to TKR highlights its potential as an effective imaging biomarker for knee osteoarthritis.

T1Gd is reduced in bone marrow lesions overlying cartilage in the hip.

OBJECTIVE: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip. RESEARCH QUESTION: is T1Gd lower in areas of cartilage overlying BMLs in the hip? DESIGN: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds. Proton-density weighted fat-suppressed and delayed Gadolinium Enhanced MR Imaging of Cartilage (dGEMRIC) images were acquired to locate BMLs and quantify hip cartilage health. BML and cartilage images were registered and cartilage was separated into BML overlying and surrounding regions. Mean T1Gd was measured in 32 participants with BMLs in both cartilage regions and in matched regions in 32 age- and sex-matched controls. Mean T1Gd in the overlying cartilage was compared using linear mixed-effects models between BML and control groups for acetabular and femoral BMLs, and between cystic and non-cystic BML groups. RESULTS: Mean T1Gd of overlying cartilage was lower in the BML group compared to the control group (acetabular: -105 ms; 95% CI: -175, -35; femoral: -8 ms; 95% CI: -141, 124). Mean T1Gd in overlying cartilage was lower in cystic compared to non-cystic BML subjects, but the confidence interval is too large to provide certainty in this difference (-3 [95% CI: -126, 121]). CONCLUSIONS: T1Gd is reduced in overlying cartilage in hips from a population-based sample of adults aged 20-49, which suggests BMLs are associated with local cartilage degeneration in hips.

Osteoarthritis Bone Marrow Lesions.

Assessment and treatment of Bone Marrow Lesions (BMLs) could ultimately make step changes to the lives of people with osteoarthritis (OA). We here review the imaging and pathological characteristics of OA-BMLs, their differential diagnosis and measurement, and cross-sectional and longitudinal associations with pain and OA structural progression. We discuss how biomechanical and cellular factors may contribute to BML pathogenesis, and how pharmacological and non-pharmacological interventions that target BMLs might reduce pain and OA structural progression. We critically appraise semiquantitative and quantitative methods for assessing BMLs, and their potential utilities for identifying people at risk of symptomatic and structural OA progression, and evaluating treatment responses. New interventions that target OA-BMLs should both confirm their importance, and reduce the unacceptable burden of OA.

Comparison of evaluation metrics of deep learning for imbalanced imaging data in osteoarthritis studies.

PURPOSE: To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies. MATERIALS AND METHODS: This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance. RESULTS: In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1. CONCLUSION: The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues.

Preoperative patellar bone marrow lesions with full thickness cartilage defects correlate with residual anterior knee pain in total knee arthroplasty without patellar resurfacing.

PURPOSE: Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA. METHODS: This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups. RESULTS: Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups. CONCLUSIONS: The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA. LEVEL OF EVIDENCE: III.

Larger bone marrow lesion volume before medial open-wedge high tibial osteotomy correlates with better improvement of clinical scores in patients with knee osteoarthritis.

PURPOSE: This study evaluated the clinical outcomes of medial open-wedge high tibial osteotomy (MOWHTO) and bone marrow lesion (BML) scores and volumes. The hypotheses were that quantitative BML volume is more associated with clinical outcomes of MOWHTO than qualitative BML evaluations, and pre-operative BML volume is associated with the improvement of clinical outcomes. METHODS: Patients who underwent MOWHTO were retrospectively enrolled. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was recorded before the initial surgery and at plate removal surgery. Using pre-operative short-time inversion recovery magnetic resonance imaging, BMLs were evaluated using three qualitative scores, reflecting the maximum length, proportion, and intensity of BML. For quantification, BMLs of the femur and tibia were separately defined as lesions with a threshold greater than the mean signal intensity plus two standard deviations, using the corresponding lateral condyles as controls. The association between the KOOS scales and BML scores/volume was evaluated using Spearman's correlation coefficient. Multivariate linear regression analyses for post-operative KOOS scales were performed using the tibial BML volume as one of the four independent variables. RESULTS: The final analysis included 40 MOWHTO cases. Two qualitative BML scores correlated only with pre-operative KOOS sports. Femoral and tibial BML volumes were correlated with post-operative KOOS QOL (ρ = 0.40, p = 0.01) and sports (ρ = 0.36, p = 0.02), respectively. Tibial BML volume was significantly correlated with all five delta KOOS scales (ρ = 0.39-0.51, p = 0.01-0.001), however, femoral BML volume was only correlated with delta KOOS QOL (ρ = 0.41, p = 0.01). In multivariate analyses, tibial BML volume was a significant positive predictor for every post-operative KOOS scale, while post-operative % mechanical axis was also a positive significant variable, except post-operative KOOS pain. CONCLUSION: Tibial BML volume was positively correlated with one post-operative KOOS scale and all delta KOOS scales. A larger pre-operative tibial BML and appropriate alignment correction were associated with a better post-operative KOOS scales. Pre-operative large BML had no negative influence on post-operative clinical outcomes; hence, surgeons need not hesitate to perform MOWHTO in patients with large BMLs in the medial condyles. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Lower bone mineral density can be a risk for an enlarging bone marrow lesion: A longitudinal cohort study of Japanese women without radiographic knee osteoarthritis.

OBJECTIVES: The aim is to elucidate the relationship between bone mineral density (BMD) at baseline and the change of bone marrow lesion (BML) during a 2-year follow-up (2YFU) period. METHODS: Seventy-eight female participants (mean age: 54.9 ± 9.6 years) without radiographic knee osteoarthritis were eligible. Based on right-knee magnetic resonance imaging, maximum BML area (BMLa) was calculated by tracing the BML border. The change in BMLa was defined using the following formula: [2YFU] - [Baseline] = ΔBMLa. Positive ΔBMLa was defined as enlarged; negative ΔBMLa was defined as regressed. Dual-energy X-ray absorptiometry was performed to measure the BMD of distal radius. Young adult mean [YAM (%)] of the BMD was used for statistical analysis. Linear regression analysis was conducted with ΔBMLa as the dependent variable and YAM as the independent variable. Receiver operating characteristic curve and logistic regression analyses were conducted for YAM to predict the prevalence of BML enlargement or regression. RESULTS: Twenty-six (33.3%) patients had enlarged BMLa, 12 (15.4%) participants showed regressing BMLa, and 40 (51.3%) patients remained stable. YAM was negatively associated with ΔBMLa (ß: - 0.375, P = 0.046). The best predictor of BML enlargement risk was 85% (odds ratio: 8.383, P = 0.025). CONCLUSIONS: Lower BMD could predict BML enlargement during a 2YFU period.

Greater medial proximal tibial slope is associated with bone marrow lesions in middle-aged women with early knee osteoarthritis.

BACKGROUND: Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on BML, including the spreading root sign (SRS), in women without radiographic knee osteoarthritis (OA). It was hypothesized that varus alignment and a greater posterior tibial slopes (PTS) are associated with BML. MATERIALS AND METHODS: A total of 359 female volunteers without knee OA who were participants in the Iwaki Health Promotion Project in 2017 or 2019 were enrolled. Participants were divided into the non-OA and early knee OA (EKOA) groups based on the Luyten's classification criteria. The presence of pathological cartilage lesions, BMLs, attritions, meniscal lesions and effusions was scored on T2-weighted fat-suppressed magnetic resonance imaging (MRI) according to the Whole-Organ MRI Scoring system. The medial proximal tibial angle (MPTA) and medial and lateral PTS (MPTS and LPTS, respectively) were measured. Regression and receiver operating characteristic (ROC) analyses were performed to reveal the relationship between BMLs and proximal tibial morphological parameters. RESULTS: Of the 359 participants, 54 (15%) were classified as having EKOA. The prevalence of cartilage lesions, BMLs, attritions, meniscal lesions and effusions was higher in the EKOA group than in the non-OA group. The two groups had no significant difference in the proximal tibial parameters. Regression analysis revealed that age and a smaller MPTA were associated with BML in both groups. Attrition (p = 0.029) and the MPTS (p = 0.025) were positively associated with BML in the EKOA group. CONCLUSION: The prevalence of BMLs was higher in women with EKOA and correlated with the varus and greater posterior slopes in those without radiographic knee OA. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Percussion test: description and diagnostic accuracy of a new manual test for bone marrow edema of the knee.

BACKGROUND: Prompt diagnosis of bone marrow lesion (BML) is difficult but critical for correct treatment. Magnetic resonance imaging is the gold standard, although expensive and time consuming. Simple and reliable clinical test for BML detection is lacking. Aim of the study is to describe a new manual clinical test called Percussion Test (PT) and to statistically determine its diagnostic accuracy in BML, compared to MRI imaging. METHODS: After evaluation of the inclusion and exclusion criteria, 218 consecutive patients with unilateral knee pain and age comprised between 18 and 80 years old were enrolled in our observational prospective study. Informed consent was obtained for each patient. After medical history collection, PT was performed by a single operator as described. MRI was performed in the affected knee to detect the presence of BML. Coherence in PT and MRI assessment was evaluated in each quadrant of the knee via contingency tables, as sensitivity, specificity, NPV, PPV and diagnostic accuracy were calculated. RESULTS: No correlation with a positive PT was demonstrated for the covariables gender (p = 0.156), age (p = 0.272) and BMI (p = 0.639). PT showed a sensitivity ranging from 60.6 (40.6-80.6) to 79.5 (63.0-96.0) and a specificity ranging from 85.7 (80.0-91.5) to 96.0 (93.1-98.9) depending on knee quadrant. Diagnostic accuracy ranged from 81.6 (75.9-86.6) to 89.4 (84.6-93.2), and p-value was < 0.00001 in a chi-squared analysis for all quadrants. CONCLUSIONS: PT showed sensitivity and specificity values that are comparable with other clinical tests routinely adopted in clinical practice. In the absence of other reliable clinical test, PT has the potential to become a useful bedside tool in the diagnosis and management of BMLs.

Bone marrow lesion severity was associated with proximal tibial inclination in early knee osteoarthritis.

PURPOSE: This study aimed to investigate the effect of tibial plateau (TP) inclination and serum bone metabolic markers on bone marrow lesion (BML) in the general Japanese population with early knee osteoarthritis (EKOA). METHODS: A total of 441 female volunteers who participated in the Iwaki Health Promotion Project in 2017 were enrolled. Participants without radiographic abnormalities were divided into normal and EKOA groups according to the Luyten's classification criteria for EKOA. The medial proximal tibial angle (MPTA), growth plate-TP angle, and growth plate-medial tibial plateau (MTP) angle were measured on standing anteroposterior radiographs of the knees. BML severity on T2-weighted fat-suppressed magnetic resonance imaging (MRI) was scored using the Whole-Organ MRI Score method. Serum levels of N-telopeptide of type I collagen, tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, pentosidine, and homocysteine were assessed. Linear regression analysis was conducted to investigate the relationship between proximal tibial inclination, BML, and serum bone metabolic markers. RESULTS: The growth plate was observed in 309 (70%) participants, and 48 (16%) participants had EKOA. The mean MPTA, growth plate-TP angle, and growth plate-MTP angle were 86.1 ± 5.9°, 3.6 ± 1.1°, and 9.9 ± 2.6°, respectively. The MPTA was negatively correlated with the growth plate-TP and growth plate-MTP angles (p = 0.006, p < 0.001). Participants with EKOA who had BML exhibited greater growth plate-MTP angle than those who did not (p = 0.018). Regression analysis revealed that BML severity was positively associated with MPTA (p = 0.036) and a bone formation marker (p = 0.045). CONCLUSION: BML severity was positively associated with proximal tibial inclination and serum TRACP-5b level in participants with EKOA and normal knees, respectively. Assessment of proximal tibial inclination may provide insight into potential BML risk. Residual medial tibial inclination may potentially result in knee pain and symptoms in EKOA. LEVEL OF EVIDENCE: III.

Changes in Bone Marrow Lesions Following Root Repair Surgery Using Modified Mason-Allen Stitches in Medial Meniscus Posterior Root Tears.

Root repair can prevent osteoarthritis (OA) by restoring hoop tension in medial meniscus posterior root tears (MMPRTs). This study aims to investigate bone marrow edema (BME) lesions known to be associated with OA following MMPRTs. Methods: Thirty patients with transtibial pull-out repair were recruited. Subchondral BME lesions were evaluated using magnetic resonance imaging (MRI) at 1-year follow-ups. Participants were categorized into three groups: no change of BME lesions (group one), improved BME lesions (group two) and worsened BME lesions (group three). Clinical scores and radiological outcomes, specifically Kellgren-Lawrence grade, medial joint space width and cartilage grade and meniscal extrusion were evaluated and compared between groups. Results: After surgery, twenty-three patients with no BME, three patients with BME lesions on the medial femoral condyle, one patient with BME lesions on the medial tibia plateau and three patients with BME lesions on both were investigated. A total of 20 patients in group one (66.7%) showed no change in BME lesions. In group two, seven patients (23.3%) presented with improved BME lesions. Only three patients (10%) showed worsened BME lesions (group three). Moreover, Lysholm scores and the rate of progression of cartilage grades were significantly worse in group three patients. Meniscal extrusion was significantly reduced in group two, whereas extrusion was significantly progressed in group three. Conclusion: Patients with worsened BME lesions showed less favorable outcomes than other patients. A decrease in meniscal extrusion can have a positive effect on BME lesions after root repair.

Correlation between the subchondral bone marrow lesions and cartilage repair tissue after matrix-associated autologous chondrocyte implantation in the knee: a cross-sectional study.

BACKGROUND: The contribution of the subchondral bone in the development and progression of osteoarthritis (OA) has long been recognized, but its role in cartilage repair procedures has only recently attracted more attention. PURPOSE: To explore the correlation between the cartilage repair tissue (RT) and the subchondral bone marrow lesions (BMLs) after matrix-associated autologous chondrocyte implantation (MACI) in the knee joint. MATERIAL AND METHODS: A total of 30 patients who underwent MACI in the knee from January 2015 to June 2018 and follow-up magnetic resonance imaging (MRI) scan were recruited in this study. The MRI results of cartilage RT were evaluated using T2* relaxation time. Subchondral BMLs were also qualitatively evaluated by use of the two-dimensional proton density-weighted fat-suppressed (2D-PD-FS) and three-dimensional dual-echo steady-state (3D-DESS) sequences. RESULTS: The univariate analysis displayed a significant negative correlation between subchondral BMLs and cartilage RT (P < 0.01). In the minimally adjusted model (only age, sex, and body mass index [BMI] adjusted), the results did not show obvious changes (ß = -6.54, 95% confidence interval [CI] = -10.99 to -2.09; P = 0.008). After adjustment for the full models (age, sex, BMI, defect size, combined injury, and preoperative duration of symptoms adjusted), the connection was also detected (ß = -6.66, 95% CI -11.82 to -1.50; P = 0.019). CONCLUSION: After MACI, the subchondral BMLs are significantly correlated with cartilage RT-T2* relaxation time. The role of subchondral bone in cartilage repair procedures should not be underestimated.

Validation of a new topographic classification of bone marrow lesions in the knee: the six-letter system.

PURPOSE: The aim of this study was to propose and validate a new six-item topographical classification of knee bone marrow lesions in coronal MRI images, to provide an easy-to-use aid to describe their location in a more reproducible and accurate way. METHODS: This study was conducted in four phases. The first was to do a literature search for methods of describing bone marrow lesions in MRI of the knee. The second was creation of a six-area topographic classification of bone marrow lesions in coronal MRI of the knee. The third phase was selection of cases with bone marrow lesions on knee MRI performed in a single hospital between January of 2017 and December of 2018. The fourth phase was categorization of the bone marrow lesions' location according to the new proposed classification by three independent examiners, two orthopedic surgeons and one radiologist. Patient's demographic data and associated lesions were collected. The inter-observer and intra-observer reliability of the proposed classification was then calculated. RESULTS: MRI examination of 4000 patients were studied and in 520 patients a total of 666 bone marrow lesions were identified and their location classified using the new system. The inter-observer and intra-observer reliability analysis found a Fleiss' Kappa value of 0.96 (0.95-0.97) and 0.97 (0.96-0.97), respectively, confirming the high reproducibility of the proposed classification. CONCLUSIONS: The proposed six-location classification of bone marrow lesions is highly reproducible and can help researchers develop studies and share information in a more accurate and reliable way. The correct classification of bone marrow lesions can lead to a more accurate description of this pathology and help clinicians to propose appropriate therapies for this group of patients. LEVEL OF EVIDENCE: V.

Younger age increases the risk of sustaining multiple concomitant injuries with an ACL rupture.

PURPOSE: Anterior cruciate ligament (ACL) tears have a major impact on the individual and society. Long term effects may be mediated by injuries that occur concurrently to the ACL tear. The purpose of this study was to describe in a nationwide cohort the traumatic meniscal injuries and bone marrow lesions concomitant to ACL tears, their age and sex distribution and the rate any association with ACL reconstruction. METHODS: All ACL tears in Iceland from 2006 to 2011 and their concomitant bone marrow lesions and meniscal injuries were identified from MRI reports. These injuries were further classified by location, sex and age. The cohort was divided into under 17, 17-29, 30-49 and above 50 to reflect likely differences in the mechanisms of injury and risk factors that may vary with age. Data from the Icelandic Social Insurance Administration were used identify all those who were operated. Descriptive analysis was performed to show the proportion of ACL injured knees sustaining concomitant injuries and how these injuries varied with age, sex, and subsequent treatment RESULTS: 1365 knees with ACL ruptures were included. Only 13% of knees had no concomitant injury identified. Overall, 57% of knees had a bone marrow lesion in at least one location and 70% of knees had at least one traumatic meniscal injury. A greater number of combined lateral tibial and femoral bone marrow lesion was seen in younger age groups (χ2 (3) = 113.32, p < 0.0001). Bruises in the medial compartment were the least common concomitant injuries. More injuries were related to higher chances of ACL reconstruction (OR 1.6, 95% CI 1.4-1.7). Age was associated with risk of all injury types and locations with older age generally being associated with fewer injuries. CONCLUSION: In an ACL ruptured cohort, the overall incidence of BMLs may be lower and meniscus injuries higher than previously reported. However, these injuries are more prevalent in the younger cohort potentially resulting in a poorer long-term prognosis. Knowledge of the association between age and concomitant injuries will help guide rehabilitation. LEVEL OF EVIDENCE: II.

Diagnostic accuracy of dual-energy CT for detection of bone marrow lesions in the subacutely injured knee with MRI as reference method.

BACKGROUND: Dual-energy computer tomography (DECT) can detect post-traumatic bone marrow lesions. Prospective studies of the knee with large numbers of participants and intra-observer agreement assessment are limited. PURPOSE: To investigate the diagnostic accuracy of DECT in detecting bone marrow lesions as well as estimating the bone marrow lesion volume in patients with suspected anterior cruciate ligament trauma with magnetic resonance imaging (MRI) as reference standard. MATERIAL AND METHODS: Forty-eight consecutive patients with suspected anterior cruciate ligament injury were imaged bilaterally with DECT within a mean of 25 days (range 4-55 days) following injury and MRI within seven days of DECT. Two readers analyzed DECT virtual non-calcium-blinded images. Consensus MRI was reference standard. Intra- and inter-observer agreement were determined using weighted kappa statistics. Sensitivity, specificity, and negative and positive predictive values were calculated. Bone marrow lesion volumes were measured; for comparison, intra-class correlation coefficient was used. RESULTS: The 48 patients (26 men, 22 women; mean age 23 years, age range 15-37 years) were imaged bilaterally yielding 52 knees with bone marrow lesions, of which 44 were in the femur and 41 were in the tibia. Intra- and inter-observer agreement to detect bone marrow lesions was moderate and fair to moderate (κ 0.54-0.66, 95% confidence interval [CI] 0.39-0.80 and 0.37-0.41, 95% CI 0.20-0.57) and overall sensitivity and specificity were 70.1% and 69.1%, respectively. Positive and negative predictive values were 72.9% and 66.1%, respectively. Bone marrow lesion volumes showed excellent intra- and inter-observer agreement (0.83-0.91, 95% CI 0.74-0.94 and 0.76-0.78, 95% CI 0.57-0.87). CONCLUSION: The diagnostic performance of DECT to detect bone marrow lesions in the subacutely injured knee was moderate with intra- and inter-observer agreement ranging from moderate to substantial and fair to moderate. Bone marrow lesion volume correlation was excellent.

Zoledronic acid is more efficient than ibandronic acid in the treatment of symptomatic bone marrow lesions of the knee.

PURPOSE: The purpose of this study was to determine the efficacy and tolerability of different antiresorptive therapeutic regimens for treating symptomatic bone marrow lesions (BML) of the knee. METHODS: Patient records of 34 patients with radiologically diagnosed, painful BML of the knee treated with either a bisphosphonate (zoledronic, ibandronic, or alendronic acid) or with a human monoclonal antibody (denosumab) were retrospectively evaluated. Response to treatment was assessed, as change in patient-reported pain, by evaluation of BML expansion on MRI using the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and by laboratory analysis of bone turnover markers: C-terminal cross-linking telopeptide (CTx) and procollagen type 1 amino-terminal propeptide (P1NP). Tolerability was evaluated by documentation of adverse reactions. RESULTS: Zoledronic acid was more or at least equally effective as the other treatment regimens with response to treatment in 11 of 12 patients (92%). The highest rate of adverse events was noted in 4 of 12 patients (33%) treated with zoledronic acid. CTx and WORMS differentiated well between responders and non-responders, whereas P1NP failed to do so. Changes in pain correlated moderately with change in WORMS (r = - 0.32), weakly with change in CTx (r = - 0.07), and not at all with change in P1NP. CONCLUSION: Zoledronic acid appeared to be more effective than other antiresorptive medications-at the cost of more frequent adverse events. While radiological and laboratory evaluation methods may allow for objective treatment monitoring, they appear to capture different dimensions than patient-reported pain. LEVEL OF EVIDENCE: III.

Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration.

OBJECTIVE: The aim of this study was to investigate how bone microstructure within bone marrow lesions (BMLs) relates to the bone and cartilage across the whole human tibial plateau. DESIGN: Thirty-two tibial plateaus from patients with osteoarthritis (OA) at total knee arthroplasty and eleven age-matched non-OA controls, were scanned ex vivo by MRI to identify BMLs and by micro CT to quantitate the subchondral (plate and trabecular) bone microstructure. For cartilage evaluation, specimens were processed histologically. RESULTS: BMLs were detected in 75% of the OA samples (OA-BML), located predominantly in the anterior-medial (AM) region. In contrast to non-OA control and OA-no BML, in OA-BML differences in microstructure were significantly more evident between subregions. In OA-BML, the AM region contained the most prominent structural alterations. Between-group comparisons showed that the AM region of the OA-BML group had significantly higher histological degeneration (OARSI grade) (P < .0001, P < .05), thicker subchondral plate (P < .05, P < .05), trabeculae that are more anisotropic (P < .0001, P < .05), well connected (P < .05, P = n.s), and more plate-like (P < 0.05, P < 0.05), compared to controls and OA-no BML at this site. Compared to controls, OA-no BML had significantly higher OARSI grade (P < .0001), and lower trabecular number (P < .05). CONCLUSION: In established knee OA, both the extent of cartilage damage and microstructural degeneration of the subchondral bone were dependent on the presence of a BML. In OA-no BML, bone microstructural alterations are consistent with a bone attrition phase of the disease. Thus, the use of BMLs as MRI image-based biomarkers appear to inform on the degenerative state within the osteochondral unit.

Bone marrow lesion is associated with disability for activities of daily living in patients with early stage knee osteoarthritis.

Osteoarthritis of the knee (knee OA) induces pain, loss of mobility and diminished activities of daily living (ADL). Although an understanding of the pathophysiology of early stage knee OA has been developed, the structural changes associated with disability for ADL in early stage knee OA are still unclear. The aim of the present study was to examine magnetic resonance imaging (MRI)-detected changes associated with disability for ADL in patients with early stage knee OA. One hundred and thirty-two patients with early stage medial knee OA (Kellgren-Lawrence grade ≤ 2) who first visited the outpatient clinic at our university hospital were included. They were also examined by 3.0-Tesla knee MRI. The OA-associated structural changes were scored using the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and clinical manifestations were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM). Median quartile regression was used for the analysis. Cartilage lesion, subchondral bone attrition and osteophytes were observed in all patients. Bone marrow lesions (BMLs) and synovitis were observed in 60% and 55% of the patients, respectively. Subchondral cysts and ligament changes were observed in 6% and 17% of the patients, respectively. Pain severity of the patients was associated with medial cartilage lesions (coefficient 2.50, 95% confidence interval 0.61-4.40, p < 0.01). Disability for ADL of the patients was associated with BMLs in the medial side of the knee joint (0.82, 0.21-1.02, p = 0.04). BMLs in the medial side of the knee joint were associated with disability for ADL of patients with early stage medial knee OA.

Measuring and reporting of vertebral endplate bone marrow lesions as seen on MRI (Modic changes): recommendations from the ISSLS Degenerative Spinal Phenotypes Group.

PURPOSE: The positive association between low back pain and MRI evidence of vertebral endplate bone marrow lesions, often called Modic changes (MC), offers the exciting prospect of diagnosing a specific phenotype of chronic low back pain (LBP). However, imprecision in the reporting of MC has introduced substantial challenges, as variations in both imaging equipment and scanning parameters can impact conspicuity of MC. This review discusses key methodological factors that impact MC classification and recommends guidelines for more consistent MC reporting that will allow for better integration of research into this LBP phenotype. METHODS: Non-systematic literature review. RESULTS: The high diagnostic specificity of MC classification for a painful level contributes to the significant association observed between MC and LBP, whereas low and variable sensitivity underlies the between- and within-study variability in observed associations. Poor sensitivity may be owing to the presence of other pain generators, to the limited MRI resolution, and to the imperfect reliability of MC classification, which lowers diagnostic sensitivity and thus influences the association between MC and LBP. Importantly, magnetic field strength and pulse sequence parameters also impact detection of MC. Advances in pulse sequences may improve reliability and prove valuable for quantifying lesion severity. CONCLUSIONS: Comparison of MC data between studies can be problematic. Various methodological factors impact detection and classification of MC, and the lack of reporting guidelines hinders interpretation and comparison of findings. Thus, it is critical to adopt imaging and reporting standards that codify acceptable methodological criteria. These slides can be retrieved under Electronic Supplementary Material.