Bone Marrow Lesions Score Research Articles

Survival analysis on subchondral bone length for total knee replacement.

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). 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. 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. SBL's capacity to predict the risk of progression to TKR highlights its potential as an effective imaging biomarker for knee osteoarthritis.

Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort

BackgroundThe IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.MethodsMRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.ResultsTwo hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).ConclusionsA wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA.Trial RegistrationClinicaltrials.gov identification: NCT03883568.

Novel Framework for Measuring Whole Knee Osteoarthritis Progression Using Magnetic Resonance Imaging.

We developed and validated a set of composite scores that combine quantitative magnetic resonance imaging (MRI)-based measurements of hyaline cartilage damage, bone marrow lesions (BMLs), and effusion-synovitis into composite scores. We selected 300 participants (n=100 for development cohort; n=200 for validation cohort) from the Osteoarthritis Initiative with complete clinical, radiographic, and MRI data at baseline and 24 months. We used semiautomated programs to quantify tibiofemoral and patellar cartilage damage, BML volume, and whole-knee effusion-synovitis volume. The candidate composite scores were formed by summing changes from baseline to 24 months based on prespecified methods. We evaluated the candidate composite scores for 1) the ability to differentiate groups with and without knee osteoarthritis progression (17 radiographic and patient-reported definitions), 2) sensitivity to change (standardized response means), and 3) relative performance relating to legacy outcome measures of knee osteoarthritis progression. Three of 13 developed composite scores qualified for testing in the validation cohort (ranked by sensitivity to change): whole-knee cumulative cartilage damage, unweighted total knee score, and BML plus effusion-synovitis volume. Change in cumulative cartilage damage associated with radiographic progression (Kellgren/Lawrence grade: odds ratio [OR] 1.84; joint space width progression: OR 2.11). Changes in the unweighted total knee score (OR 1.97) and BML plus effusion-synovitis score (OR 1.92) associated with Western Ontario and McMaster Universities Osteoarthritis Index knee pain progression. Two composite scores emerged, reflecting discrete domains of knee osteoarthritis progression. First, cumulative damage, which is measured by a whole-knee cartilage damage score, reflects the damage accrued over time. Second, dynamic disease activity, which is measured by a BML plus effusion-synovitis score, relates to changes in a patient's state of disease and symptoms.

MULTI‐TISSUE ASSESSMENT AND 24‐MONTH PROGRESSION OF SEMI‐QUANTITATIVE MRI BIOMARKERS OF KNEE OSTEOARTHRITIS IN THE IMI‐APPROACH COHORT

The IMI-APPROACH (Applied Public-Private Research enabling OsteoArthritis Clinical Headway) study is an exploratory, European, 5-centre, 2-year prospective follow-up cohort project. IMI-APPROACH was designed to prospectively describe pre-identified progressor phenotypes of patients with symptomatic and/or structural knee OA by use of conventional and novel clinical, imaging, and biochemical biomarkers, and to validate and refine a predictive model for progressor phenotypes based on these markers. The recruitment for IMI-APPROACH was based on rankings produced by machine-learning models that were trained using data from existing cohorts to estimate the likelihood of joint space width loss and/or increased or sustained knee pain over the course of the study from demographic data, pain scores, and radiographic features. To describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period. MRIs were acquired using 1.5T or 3T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition. 289 participants had a readable baseline scan. Participants were on average 66.6±7.1 years old and had a BMI of 28.1±5.3 kg/m². The majority (55.3%) of the knees had definite signs of radiographic OA. Any change in total cartilage MOAKS score was seen in 53.1% considering only full-grade changes and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression in 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in the ROA- compared to the non-ROA subgroup (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee). A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was significantly more common in the ROA subgroup compared to the knees without ROA. This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115770, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. See www.imi.europa.eu and www.approachproject.eu . FWR is shareholder of Boston Imaging Core Lab. (BICL),LLC. And is consultant to Calibr and Grünenthal (in thals t 36 months) CL reports other from Merck KGaA, during the conduct of the study; MK reports grants from IMI-APPROACH, grants from Dutch Arthritis Association, during the conduct of the study; other from GlaxoSmithKline, Pfizer, Merck-Serono, Kiniksa, Abbvie, outside the submitted work; FJB reports grants from Gebro Pharma, grants from BIOIBERICA, grants from AB Science, grants from Abbvie, grants from Ablynx N.V., grants from Amgen, grants from Archigen Biotech Limited, grants from Boehringer, grants from Bristol-Myers, grants from Celgene Int., grants from Eli Lilly and Company, grants from F. Hoffmann- La Roche, grants from Galapagos, grants from Gedeon, grants from Genentech, grants from Gideal Sciences, NC, grants from Glaxosmithkline, grants from Hospira, grants from INC Research UK, grants from Inventiv Health Clinical, grants from Janssen, grants from Lilly, grants from Nichi-IKO Pharmaceutical, grants from Novartis, grants from ONO Pharma, grants from Pfizer, grants from Pharmaceutical Research, grants from Regeneron, grants from Roche, grants from SA UCB Pharma, grants from Sanofi, grants from TRB Chemedica, grants from UCB Biosciences GMBH, outside the submitted work; IKH reports personal fees from AbbVie, grants from Pfizer, outside the submitted work; FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma CORRESPONDENCE ADDRESS: frank.roemer@uk-erlangen.de .

Association of Quadriceps Adiposity With an Increase in Knee Cartilage, Meniscus, or Bone Marrow Lesions Over Three Years.

To evaluate the association of fatty infiltration of the quadriceps and vastus medialis (VM) with an increase in knee cartilage, meniscus, or bone marrow lesions, using magnetic resonance imaging (MRI) in knee osteoarthritis (OA) over 3 years. Participants (n = 69) with and without radiographic knee OA underwent MRI at baseline and 3 years later. Chemical shift-based water/fat MRI was used to quantify the intramuscular fat fraction and the lean anatomical cross-sectional area (ACSA) for the VM and entire quadriceps muscles. MRI images of the knee were analyzed using the semiquantitative modified whole-organ MRI score (mWORMS) grading to assess change in lesions in the articular cartilage, meniscus, and bone marrow. Logistic regression was used to assess whether baseline quadriceps and VM fat fraction and lean ACSA were associated with an increase in mWORMS scores. Odds ratios (ORs) were adjusted for age, sex, and body mass index. Overall, of the 69 subjects, 43 (62%) had an increase in cartilage lesions (26 of 43), meniscus lesions (19 of 43), or bone marrow lesions (22 of 43) scores. The quadriceps (OR 2.13 [95% confidence interval (95% CI) 1.09-4.15]) and VM (OR 2.05 [95% CI 1.25-3.36]) fat fraction were both associated with an increase in cartilage, meniscus, or bone marrow lesion scores over 3 years. The association of quadriceps or VM lean ACSA with the outcomes was not significant. These longitudinal findings using quantitative MRI methods for assessment of muscle adiposity highlight the role of quadriceps adiposity, specifically in the VM, in knee OA progression. However, studies in larger cohorts are needed to confirm these findings.

Lateral patellar tilt and its longitudinal association with patellofemoral osteoarthritis-related structural damage: Analysis of the osteoarthritis initiative data

BackgroundIncrease in lateral patellar tilt-(LPT) can cause increased pressure on the lateral facet of the knee and can lead to patellar or femoral cartilage damage and further osseous changes. This study aims to test the hypothesis whether there is an association between increased LPT and MRI-based patellofemoral osteoarthritis-(OA) features at baseline and their worsening over a 2-year follow-up in participants of the Osteoarthritis Initiative-(OAI). MethodsRecorded clinical and imaging data of 600 participants in the FNIH-OA biomarkers consortium was extracted from its database. The LPT-(as the angle betweenthe longest patella diameter and posterior aspect of condyles) was measured using theaxial knee MRI. Associations of LPT (every 5° increase) with MRI OA Knee Scoring-(MOAKS) for OA-related features, including cartilage and bone marrow lesions (BMLs) in addition to knee cartilage volume at baseline and their worsening after 2-year follow-up were assessed using regression models adjusted for several possible confounders. ResultsThe mean LPT angle in this sample was 8.84° ± 5.19. In baseline, higher LPT was associated with lower cartilage volumes and higher cartilage lesions and BMLs MOAKS scores in the lateral trochlear and patellar subregions. Over the follow-ups, subjects with higher LPT measures in the baseline showed higher odds of experiencing BML score worsening in the lateral trochlear subregion-(OR:1.25[1.01–1.56]) over the 2-year follow-ups. ConclusionsIncrease in LPT measures may be associated with OA-related features in the trochlear subregion. Therefore, aside from its use as an indicator of patellofemoral instability syndrome, LPT may be associated with longitudinal progression of patellofemoral OA.

Reliability and sensitivity to change of bone marrow lesion scores using the knee inflammation MRI scoring system (KIMRISS) before and after high tibial osteotomy

Purpose: Bone marrow lesions (BMLs) are an important feature of knee osteoarthritis (OA) and are associated with increased risk of cartilage damage and pain. The Knee Inflammation MRI Scoring System (KIMRISS) is a semi-quantitative grading tool used to evaluate measures of inflammation in patients with knee OA. The KIMRISS allows for readers to record scoring decisions in a rapid manner, on a convenient web-based interface. The objectives of this study were to investigate: 1. Inter-rater reliability of KIMRISS BML scores including expert readers and a trainee reader, and 2.

Higher Serum Levels of Resistin Are Associated With Knee Synovitis and Structural Abnormalities in Patients With Symptomatic Knee Osteoarthritis

ObjectiveResistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. DesignA prospective cohort study. Setting and participantsPatients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79; female 46.5%) participated. MeasuresAll measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. ResultsSerum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Conclusion and implicationsHigher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways.

Tibiofemoral joint structural change from 2.5 to 4.5\u2009years following ACL reconstruction with and without combined meniscal pathology

BackgroundPeople who have had anterior cruciate ligament reconstruction (ACLR) are at a high risk of developing tibiofemoral joint (TFJ) osteoarthritis (OA), with concomitant meniscal injury elevating this risk. This study aimed to investigate OA-related morphological change over 2 years in the TFJ among individuals who have undergone ACLR with or without concomitant meniscal pathology and in healthy controls. A secondary aim was to examine associations of baseline TFJ cartilage defects and bone marrow lesions (BML) scores with tibial cartilage volume change in ACLR groups.MethodsFifty seven ACLR participants aged 18–40 years (32 isolated ACLR, 25 combined meniscal pathology) underwent knee magnetic resonance imaging (MRI) 2.5 and 4.5 years post-surgery. Nine healthy controls underwent knee MRI at the ~ 2-year intervals. Tibial cartilage volume, TFJ cartilage defects and BMLs were assessed from MRI.ResultsFor both ACLR groups, medial and lateral tibial cartilage volume increased over 2 years (P < 0.05). Isolated ACLR group had greater annual percentage increase in lateral tibial cartilage volume compared with controls and with the combined group (P = 0.03). Cartilage defects remained unchanged across groups. Both ACLR groups showed more lateral tibia BML regression compared with controls (P = 0.04). Baseline cartilage defects score was positively associated with cartilage volume increase at lateral tibia (P = 0.002) while baseline BMLs score was inversely related to medial tibia cartilage volume increase (P = 0.001) in the pooled ACLR group.ConclusionsTibial cartilage hypertrophy was apparent in ACLR knees from 2.5 to 4.5 years post-surgery and was partly dependent upon meniscal status together with the nature and location of the underlying pathology at baseline. Magnitude and direction of change in joint pathologies (i.e., cartilage defects, BMLs) were less predictable and either remained stable or improved over follow-up.

Association of bone marrow lesions localisation with weight bearing pain in people with knee osteoarthritis: data from the osteoarthritis initiative

Purpose: Subchondral bone contributes to pain in knee osteoarthritis (OA). OA structural change particularly affects weight-bearing components of the joint, most notably the medial femorotibial compartment in people with varus angulation. Subchondral bone marrow lesions (BMLs) detected on MRI in knee OA are strongly associated with pain. BMLs typically occur in regions of the joint with the most severe structural change, for example, full-thickness cartilage lesions. However, the association between subchondral BMLs in weight-bearing components and weight-bearing pain has not been clarified. The purpose of this study was to assess association between BMLs location and weight bearing knee pain using data from the Osteoarthritis Initiative (OAI). We hypothesized that BMLs at the medial femorotibial joint compartment were associated with weight bearing pain, independent of non-weight bearing pain, and that changes in size of the BMLs over time were associated with change in weight bearing pain. Methods: The OAI is a publicly available multi-center, longitudinal, prospective observational study of knee OA. We examined the knees of OAI participants with MRI readings using the MRI Osteoarthritis Knee Score (MOAKS). BMLs, articular cartilage, osteophytes, Hoffa’s synovitis, effusion, meniscal morphology and anterior cruciate ligament tears were scored using the MOAKS, and femorotibial angle (FTA) and Body Mass Index (BMI) were examined. BML scores using MOAKS were available for 4 articular sub-regions (median and lateral femorotibial, and medial and lateral patellofemoral joint) and the subspinous region. Knee pain was assessed at baseline (cross-sectional) and baseline and 2 years (longitudinal) using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We defined weight bearing pain as the sum of three WOMAC questions (pain on climbing stairs, on walking, and on standing) and non-weight bearing pain as the sum of two WOMAC questions (pain in bed and with sitting/lying down). Negative binomial regression was performed, using SPSS version 23 software. Results: 1412 participants were included in the cross-sectional analysis (from OAI project 22, 30 and 65), mean age 62 (±9) years, mean BMI 30 (±5), 61% female, median weight and non-weight bearing WOMAC score 2 (IQR 0, 4) and 0 (IQR 0, 1), and median total BML score 3 (IQR 1, 6). Weight bearing pain was associated with total BML score was r = 0.35 (p < 0.0001), and with BML scores at medial (r=0.29, p < 0.0001) and lateral (r=0.09, p = 0.0009) femorotibial joint compartments. Weight bearing pain was also associated with BML score at medial and lateral patellofemoral joint compartments (r = 0.03, p = 0.3 and 0.13, p < 0.0001, respectively). The association between weight bearing pain and BML scores at medial femorotibial and lateral patellofemoral joint compartments remained significant after adjusting for non-weight bearing pain, age, sex, BMI, FTA, BML scores at the other 4 joint compartments and the other OA related MRI features (osteophyte score, cartilage defect score, medial meniscus extrusion, anterior cruciate ligament tears, synovitis and effusion) (Table 1). 600 participants were included in the longitudinal study (OAI project 22), mean age 62 (± 9) years, mean BMI 31 (± 5), 57% female, median weight and non-weight bearing WOMAC score 1 (IQR 0, 3) and 0 (IQR 0, 1), and median total BML score 3 (IQR 2, 5). From baseline to 2 years, the changes in the mean weight and non-weight bearing 0.5 (±2.2) and 0.1 (±1.4), and mean total BML score were 0.7 (±1.9). The correlation between changes in weight bearing pain and changes in total BML score was r = 0.13 (p = 0.002); between changes in weight-bearing pain and BML score at medial and lateral femorotibial joint compartment were r = 0.16 (p < 0.0001) and -0.03 (p = 0.45), between changes in weight-bearing pain and changes in BML score at medial and lateral patellofemoral joint compartment were r = 0.04 (p = 0.3) and -0.03 (p = 0.5). The association between the changes in BML score at medial femorotibial joint compartment and changes in weight-bearing pain remained significant after adjusting for changes in non-weight bearing pain, age, sex, BMI, BML change at the other four joint compartments and osteophyte score change (Table 2). Conclusions: In this cross sectional and longitudinal study, BMLs at medial femorotibial joint compartment in varus knee OA participants were highly associated with the severity and the change in severity of weight bearing pain. The associations persisted when mutually adjusting for other feature of OA related MRI features, and adjusting for non-weight bearing pain, age, sex and BMI. Our findings suggest that BMLs in weight-bearing areas might contribute to weight bearing pain. Reducing BMLs or weight bearing in joint compartments with BMLs are candidate treatment targets in knee OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Association of Knee Effusion Detected by Physical Examination With Bone Marrow Lesions: Cross-Sectional and Longitudinal Analyses of a Population-Based Cohort.

To determine the association of effusion detected by physical examination with the prevalence of bone marrow lesions (BMLs) on magnetic resonance imaging (MRI), and the incidence/progression of BMLs over 3 years in subjects with knee osteoarthritis. A population-based cohort with knee pain (n = 255) was assessed for effusion on physical examination. On MRI, BMLs were graded 0-3 (none, mild, moderate, severe), and incidence/progression was defined as a worsening of the sum of BML scores over 6 surfaces by ≥1 grade. We analyzed the full cohort and a mild disease subsample with a Kellgren/Lawrence (K/L) grade <3. Cross-sectional logistic and longitudinal exponential regression analyses were performed, adjusted for age, sex, body mass index (BMI) and pain. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for effusion detected by physical examination versus BMLs (prevalence and incidence/progression). The weighted mean age was 56.7 years, the mean BMI was 26.5, 56.3% were women, 20.1% had effusion on physical examination, and 80.7% had a K/L grade <3. Effusion on physical examination was significantly associated with prevalent BMLs in the full cohort (odds ratio [OR] 6.10 [95% confidence interval (95% CI) 2.77-13.44]) and in the K/L grade <3 cohort (OR 6.88 [95% CI 2.76-17.15]). In the full cohort, sensitivity, specificity, PPV, and NPV were 34.6, 92.5, 79.9, and 62.1%, respectively, and in the K/L <3 cohort 31.7, 94.0, 75.5, and 70.1%, respectively. Longitudinally, effusion on physical examination was not significantly associated with BML incidence/progression in the full cohort (hazard ratio [HR] 1.83 [95% CI 0.95-3.52]) or in the K/L grade <3 cohort (HR 1.73 [95% CI 0.69-4.33]). In the two cohorts, sensitivity, specificity, PPV, and NPV were 32.0, 82.2, 42.2, and 74.9%, respectively, and 21.2, 85.6, 30.1, and 78.8% respectively. BMLs on MRI can be predicted from physical examination effusion cross-sectionally, with a high PPV of 79.9%. Assessment for knee effusion on physical examination is useful for determining potential candidates with BMLs before costly MRI screening for recruitment into clinical trials.

Association of patella alta with worsening of patellofemoral osteoarthritis-related structural damage: data from the Osteoarthritis Initiative

To determine the association between Insall-Salvati ratio (ISR), a measure of patella alta, and worsening of Magnetic Resonance Imaging (MRI)-based osteoarthritis (OA)-related patellofemoral joint structural damages over 24-month in participants of the Osteoarthritis Initiative (OAI). Using weighted random sampling method, we selected a sample of 500 knees (from 1,677 knees with available baseline and 24-months MRI OA Knee Score (MOAKS) measurements), which is OAI-representative regarding knee OA-related factors (i.e., baseline age, sex, body mass index (BMI), and radiographic Kellgren-Lawrence grading). The ISR was measured in all enrolled knees using baseline sagittal 3T-MRI plane by three radiologists. Baseline and 24-month MOAKS variables for patellofemoral bone marrow lesions (BMLs), cartilage damages, and osteophytes were extracted, and the associations between ISR and 24-month worsening of these 3T-MRI features were evaluated using multivariable regression models. After computing receiver operating characteristic curves, the optimal cutoff point of ISR for indicating worsening of patellofemoral OA was determined. P-values were adjusted for multiple comparisons and false discovery rate (FDR) adjusted P-values were reported. In this longitudinal analysis, 24-month worsening of BML (odds ratio [OR] (95% confidence interval [95% CI]):11.18 (3.35-39.6), adjusted-p-value:<0.001) and cartilage scores (OR:7.39 (1.62-34.71), adjusted-p-value:0.042) in lateral patella was associated with higher baseline ISR. However, higher ISR was not statistically associated with medial patellar or medial and lateral trochlear BML or cartilage scores worsening. We determined the optimal cutoff point of ISR≥1.14 (95% CI: 1.083-1.284) for predicting lateral patellofemoral OA-related structural damages worsening over 24-months (sensitivity:73.73%; specificity: 66.67%). Given the uncertainly surrounding the results, our overall findings suggest that ISR could be considered as a predictor of lateral patellofemoral OA-related structural damages worsening with the optimal cutoff point of ≥1.14 using knee sagittal MRI measurements.

Bone marrow lesions of the knee: longitudinal correlation between lesion size changes and pain before and after conservative treatment by extracorporeal shockwave therapy.

Bone marrow lesions (BMLs) of the knee have become a common finding on magnetic resonance imaging (MRI), leading to a growing interest in BML, not only for its potential role in the progression of several musculoskeletal conditions, but also for its clinical impact and treatment implications. At present, there is limited and conflicting evidence regarding whether or not pain may be correlated to BML size or not. To verify the longitudinal correlation between BML size and knee pain. Longitudinal. Italian Orthopedic Institute. The study sample was composed of 72 patients, 27 males and 45 females, with a mean age of 55.9±10.22 years and a mean BMI of 26.1±3.7 kg/m2. All patients presented with BMLs and acute knee pain. All 72 patients underwent a knee MRI before and 6 months after a course of high energy ESWT, in order to perform a quantitative measurement of the BML areas. KOOS (Knee Injury and Osteoarthritis Outcome Score) Pain subscale scores were obtained at the same time point. A regression analysis was performed to verify the correlation between knee BML size and KOOS pain subscale score before treatment and the correlation between the reduction of BML size and the improvement of KOOS pain score 6 months after treatment. A statistically significant correlation between the KOOS Pain subscale and the BML size (beta=-0.362 [CI95%: -0.019/-0.05], P=0.002) was demonstrated. The clinical score and BML area significantly improved after treatment (P<0.001). The clinical improvement was correlated to the BML size reduction (beta=0.254 [CI95%: 0.001/0.017], P=0.031). This study confirmed a significant correlation between the BML size and the intensity of knee pain. Furthermore, the before and after study using ESWT to treat symptomatic BMLs, revealed a correlation between size reduction of BML and KOOS pain subscale score improvement, demonstrating the utility of BML reduction as a therapeutic goal. Finally, ESWT was validated as a safe and potentially effective treatment of subchondral bone marrow lesions. Our results confirm that severity of pain is correlated with BML size, and furthermore, demonstrate that increases and decreases in the amount of pain reflect growth or reduction in BML size, respectively. This information may be useful for rehabilitation and decrease the reliance on MRIs for checking the progress of bone lesions. Absence or marked reduction of pain should allow for the resumption of weight-bearing and more strenuous exercises for an adequate musculoskeletal recovery.

The relationship between two different measures of osteoarthritis bone pathology, bone marrow lesions and 3D bone shape: data from the osteoarthritis initiative

Purpose: Magnetic resonance imaging (MRI) has provided great insights into the development of OA, and helped highlight the importance of subchondral bone pathology. Bone shape and bone marrow lesions (BMLs) represent different features of MRI-detected subchondral pathology in osteoarthritis (OA) and while BMLs are well studied the relationship between these two remains poorly understood. It is important to understand if they represent a single construct or different parts of the OA process, and to further explore their use as imaging biomarkers. The aim of this study was to determine how these features are related and how they change in OA progression. Methods: 600 participants from the FNIH Biomarkers Initiative of the OAI were included, having Kellgren–Lawrence (KL) 1, 2 or 3 at baseline and MRI data at baseline and 24 months. MRI images obtained from the OAI were scored for BMLs using the semi-quantitative MOAKS system that scores 3 features using an ordinal scale for size, number of BMLs and percentage of lesion that is a BML as opposed to a cyst. Quantitative 3D bone shape data was provided by Imorphics (Manchester, UK) using active appearance models (AAMs) applied separately for femur and tibia from 3T DESS-we images. The shape vector for each bone was calculated by taking the principal components of the mean non-OA shape and the mean OA shape and the vector was normalised by setting the mean OA shape to +1 and mean non-OA shape as −1, with each unit increase of 1 representing 1 standard deviation (SD) calculated in non-OA knees. Four BML scores were computed: “BML total size”, “BML total number”, “BML total sub regions” and BML maximum size”. At baseline the correlation between the BML scores and bone shape measures were assessed using Spearman`s correlation coefficients. The association between 3D quantitative bone shape vectors and BMLs at baseline was analysed using linear regression. Presence of a BML was defined as BML total size ≥ 1. Responsiveness was calculated for both features in 4 pre-defined progression groups and reported as standardised response means (SRMs).Due to nesting of repeated measurements within individuals, multilevel linear modelling was used to assess the longitudinal relationship between change in BML size and change in bone shape vector. Results: Mean age was 61.5, 59% were female and mean BMI was 30.7. Correlation between baseline femur shape vector and femur BML total size was r = 0.28, P < 0.001 and similar for the tibia. Linear models revealed an association between presence of a femur BML at baseline and baseline 3D femur vector in both univariable and multivariable models (adjusted coefficient 0.49, 95% CI 0.30, 0.68) indicating a more positive femur vector (indicative of “increased OA”) in individuals with BMLs at baseline, with a difference equivalent to 0.5 × SD of non-OA knees. Longitudinally bone shape demonstrated more responsiveness to change than all BML measures (SRM 0.89 vs 0.13) for femur bone shape vector vs BML total size respectively (Table 1). Univariable growth models revealed that bone shape vector tended to be more positive over time (indicating worsening) while BML total size reduced over time. Multilevel models also showed that an increase in BML size was related to a more positive bone shape vector (representing worsening OA). Conclusions: There is a relationship between bone shape and BMLs, with increasing OA bone shape vector associated with higher prevalence of BMLs. Bone shape vector demonstrated greater responsiveness than semi-quantitative BMLs over time periods typical of a clinical trial.Table 1Responsiveness of bone shape and BML measures over 24 monthsRadiographic and pain progression N = 194Radiographic progression only N = 103Pain progression only N = 103No progression N = 2002 year responsiveness, SRM (95%CI)Bone shapeFemur0.89 (0.72,1.02)1.02 (0.85,1.20)0.46 (0.31,0.61)0.61 (0.49,0.72)Tibia0.84 (0.70,0.97)0.76 (0.56,0.96)0.26 (0.07,0.43)0.47 (0.33,0.69)BMLsFemur BML total size−0.13 (−0.26,0.02)−0.15 (−0.35,0.07)−0.31 (−0.51,−0.13)−0.24 (−0.37,0.13)Femur BML total number0.38 (0.26,0.50)0.20 (−0.02,0.41)0.17 (−0.04,0.35)0.27 (0.14,0.38)Tibia BML total size0.11 (−0.02,0.26)0.14 (−0.04,0.31)−0.04 (−0.23,0.15)−0.01(−0.16,0.11)Tibia BML total number0.37 (0.24,0.51)0.31 (0.12,0.51)0.19 (0.00,0.33)0.16 (0.02,0.29)Femur BML maximum size−0.05 (−0.19,−0.09)−0.01 (−0.19,0.21)−0.20 (−0.38,0.01)−0.11 (−0.25,0.02)BML total sub regions−0.02 (−0.15,0.13)−0.03 (−0.23,0.15)−0.13 (−0.32,0.07)−0.06 (−0.20,0.08) Open table in a new tab

Associations Between Knee Effusion-synovitis and Joint Structural Changes in Patients with Knee Osteoarthritis.

To describe the associations between effusion-synovitis and joint structural abnormalities in patients with knee osteoarthritis (OA) over 24 months. A posthoc analysis using data from a randomized controlled trial in 413 patients with symptomatic OA (aged 63 ± 7 yrs, 208 women). Knee effusion-synovitis volume and score, cartilage defects, cartilage volume, and bone marrow lesions (BML) were assessed using magnetic resonance imaging. Joint space narrowing (JSN) and osteophytes were assessed using radiograph. Least significant change criterion was used to define change in effusion-synovitis volume. Knee symptoms were assessed by Western Ontario and McMaster University OA Index. Multivariable linear/logistic regression and multilevel generalized mixed-effects models were used in longitudinal analyses. Total effusion-synovitis volume increased modestly from baseline (8.0 ± 8.5 ml) to followup (9.0 ± 10.5 ml). Baseline BML, cartilage defect, JSN, and osteophyte scores were positively associated with change in effusion-synovitis volume (p < 0.05). Baseline cartilage defects and JSN were also associated with change in effusion-synovitis score (p < 0.05). However, neither baseline effusion-synovitis score nor volume consistently predicted change in the above structures except cartilage volume. In the mixed-effects models, knee effusion-synovitis was positively associated with BML (volume: β = 1.19 ml/grade; score: OR = 1.75/grade) and cartilage defects (volume: β = 1.87 ml/grade; score: OR = 2.22/grade), while negatively associated with cartilage volume loss. Change in effusion-synovitis volume was positively correlated with changes in knee pain and stiffness scores (p < 0.05). Knee cartilage and subchondral bone abnormalities predicted change in effusion-synovitis, but effusion-synovitis did not predict knee structural changes. These findings suggest that synovial inflammation is likely the result of joint structural abnormalities in established OA. ClinicalTrials.gov identifier: NCT01176344. Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.

Is superolateral Hoffa's fat pad hyperintensity a marker of local patellofemoral joint disease? - The MOST study.

To determine the relation of superolateral Hoffa's fat pad (SHFP) hyperintensity to cartilage damage and bone marrow lesions (BMLs) in the patellofemoral joint (PFJ) and tibiofemoral joint (TFJ). We used data from the 60 and 84-month study visits from the Multicenter Osteoarthritis (MOST) study. SHFP hyperintensity and Hoffa-synovitis were graded from 0 to 3. Cartilage damage and BMLs were scored in the PFJ and TFJ. Structural damage was defined as: any cartilage damage, full-thickness cartilage damage and any BML. Worsening structural damage was defined as any increase in cartilage and BML scores. Logistic regression was used to determine the relation of SHFP hyperintensity and Hoffa-synovitis (>0) to structural damage, adjusting for age, sex and body mass index (BMI). 1,094 knees were included in the study. Compared to knees without SHFP hyperintensity, those with SHFP hyperintensity had 1.2 (95% Confidence Interval (CI), 1.1-1.4), 1.7 (1.3-2.3) and 1.6 (1.3-1.9) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the lateral PFJ respectively, and 1.1 (1.0-1.2), 1.3 (1.0-1.8), and 1.2 (1.0-1.4) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the medial PFJ. SHFP hyperintensity was associated with worsening BMLs in the medial PFJ (RR: 1.4 (1.0-1.9)). In general, there was no relation between SHFP hyperintensity and TFJ outcomes. Hoffa-synovitis was associated both cross-sectionally and longitudinally with structural damage, regardless of definition, in all compartments. SHFP hyperintensity may be a local marker of PFJ structural damage.

Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis.

To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA). Patients (n=192) with symptomatic knee OA (mean 63 years, range 50-79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex® Multiplex Immunoassays with Luminex xMAP technology. Knee BMLs were scored using the modified whole organ MRI score (WORMS) from T2 weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI). Multivariable linear regression and log binominal regression were used to determine the associations between cytokines and BMLs. Baseline IL-6 (quarters) were significantly associated with total knee BMLs (P<0.01 for the trend) as well as associated with an increase in BML score (P=0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females (P=0.04 for IL-17F; P=0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males. IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women. ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.

Cross-Sectional and Longitudinal Associations Between Serum Levels of High-Sensitivity C-Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis.

To describe associations between serum high-sensitivity C-reactive protein (hsCRP), knee bone marrow lesions (BMLs), and knee pain, cross-sectionally and longitudinally, in patients with knee osteoarthritis (OA). Patients (n = 192) with symptomatic knee OA (mean age 63 years, range 50-79, women 53%) were assessed at baseline and after 24 months. Serum hsCRP was measured using enzyme-linked immunosorbent assay. Knee BMLs were scored using the modified Whole-Organ Magnetic Resonance Imaging (MRI) Score from T2-weighted fat-supressed fast spin-echo MRI. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. Quartiles of baseline serum hsCRP were associated with the presence of knee BMLs (prevalence ratio 1.07 per quartile [95% confidence interval (95% CI) 1.00, 1.15]) and total knee pain scores (β 13.66 per quartile [95% CI 2.26, 25.07]) in multivariable analyses. Longitudinally, higher baseline hsCRP was associated with an increase in BML score (risk ratio 1.37 per quartile [95% CI 1.10, 1.70]), and change in hsCRP was positively associated with change in BML score (β 0.19 [95% CI 0.05, 0.34]) in adjusted analyses. Baseline hsCRP was not associated with change in total knee pain, but change in hsCRP was positively and significantly associated with change in total knee pain (β 4.71 [95% CI 0.48, 8.94]). This became nonsignificant after adjustment for changes in BML score. In patients with knee OA, serum hsCRP is associated with knee BML scores and, to a lesser extent, pain both cross-sectionally and longitudinally, suggesting that inflammation is linked with BMLs and their associated pain.

Effect of chondroitin sulfate on cartilage volume loss and subchondral bone marrow lesions in osteoarthritis knee

Chondroitin sulfate (CS) is a major component of the extracellular matrix of many connective tissues, including cartilage, bone, skin, ligaments, and tendons. The aim of this work was to study the effect of CS treatment for short time (6 months) clinically and using MRI on cartilage volume loss, subchondral bone marrow lesions (BMLs), and synovitis in patients with primary knee osteoarthritis (OA). A total of 50 patients with primary knee OA and clinical signs of synovitis were included in this study. They were divided into two treatment groups. Group 1 included 30 patients who received two capsules of CS (structum capsule 500 mg) once daily for 6 months. Group 2 included 20 patients who received placebo once daily for 6 months. Clinical, radiological, and laboratory assessments were performed for all patients. Cartilage volume loss, subchondral BMLs, and synovial membrane thickness were assessed with MRI at baseline and after 6 months for both groups. The CS group showed significantly less cartilage volume loss compared with the placebo group after 6 months for the global knee, lateral compartment and tibial plateaus. However, there were no significant differences in the medial compartment and trochlea between the two groups. Significantly lower BML scores were found for the CS group compared with theplacebo group after 6 months, and there were no significant differences in synovial membrane thickness between the two groups. Disease symptoms were similar in both groups. CS treatment significantly reduces the cartilage volume loss and subchondral BMLs in primary knee OA after 6 months of treatment. These findings suggested a joint structure-protective effect of CS.

Intravenous neridronate in the treatment of acute painful knee osteoarthritis: a randomized controlled study.

The aim of this randomized, double-blind, placebo-controlled study was to assess the efficacy of i.v. neridronate in controlling pain in patients with acute painful knee OA. Sixty-four patients with acute knee pain (<3 months duration) suffering from knee OA with an MRI showing bone marrow lesions (BMLs) were randomized to receive either neridronate 100 mg given four times over 10 days or placebo. After 50 days the patients underwent clinical assessment and a further MRI was performed. Primary outcome was pain changes measured by a visual analogue scale (VAS; range 0-100). Secondary endpoints were WOMAC pain score, McGill pain questionnaire and 36-Item Short Form Health Survey. BMLs were evaluated by whole-organ MRI score. At the day of the last infusion the VAS decreased significantly more in the neridronate group [from 59.0 (s.d. 14.7) to 30.4 (s.d. 15.6); -48.4%; P < 0.001]. Fifty days later the VAS remained unchanged in the placebo group, while a further significant decrease was observed in the neridronate group [from 30.4 (s.d. 15.6) to 9.4 (s.d. 10.8); -69.1%; P < 0.001]. Significant improvements compared with the placebo group were found for most of the other indices of pain and quality of life. The BMLs score in the neridronate group showed significant decreases compared with basal values and those of the placebo-treated patients. Four months after the treatment, 72% of the placebo-treated patients resumed analgesic or anti-inflammatory drugs, but only 12.9% resumed treatment in the neridronate group. In patients with acute painful knee OA, four infusions of neridronate are associated with a clinically relevant pain benefit. ClinicalTrials.gov (http://clinicaltrials.gov), NCT01803360.