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SummaryObjectiveTo identify factors associated with change in femoral cartilage volume over 2 years in a cohort largely without knee radiographic osteoarthritis.MethodsA total of 252 subjects (mean 45 years, range 28–60) were used for this study. T1-weighted fat saturation magnetic resonance imaging was performed at baseline and ∼2 years later. Knee femoral condyle cartilage volume, femoral cartilage defect (0–4 scale) and tibial bone size were determined.ResultsThe total femoral cartilage volume loss was 6.3% for the 2.3-year period. Factors associated with this annual change were female gender (females vs males: −1.69%, P

Objectives: Osteoarthritis (OA) structural changes take place over decades in humans. MRI can provide precise and reliable information on the joint structure and changes over time. In this study, we investigated the reliability of quantitative MRI in assessing knee OA structural changes in the experimental anterior cruciate ligament (ACL) dog model of OA. Methods: OA was surgically induced by transection of the ACL of the right knee in five dogs. High resolution three dimensional MRI using a 1.5 T magnet was performed at baseline, 4, 8 and 26 weeks post surgery. Cartilage volume/thickness, cartilage defects, trochlear osteophyte formation and subchondral bone lesion (hypersignal) were assessed on MRI images. Animals were killed 26 weeks post surgery and macroscopic evaluation was performed. Results: There was a progressive and significant increase over time in the loss of knee cartilage volume, the cartilage defect and subchondral bone hypersignal. The trochlear osteophyte size also progressed over time. The greatest cartilage loss at 26 weeks was found on the tibial plateaus and in the medial compartment. There was a highly significant correlation between total knee cartilage volume loss or defect and subchondral bone hypersignal, and also a good correlation between the macroscopic and the MRI findings. Conclusion: This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of the joint structural changes during the development of OA in the ACL dog model. The combination of this OA model with MRI evaluation provides a promising tool for the evaluation of new disease-modifying osteoarthritis drugs (DMOADs).

To examine the long-term (6-year) effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on cartilage volume in knee osteoarthritis (OA).Participants were from the Osteoarthritis Initiative progression and incidence subcohorts, had magnetic resonance imaging (MRI) of the target knee at baseline and 6 years, joint space width1 mm, and data available on Glu/CS consumption (n = 1,593). They were stratified into 2 main groups based on whether or not they had medial meniscal extrusion at baseline. The group with meniscal extrusion (n = 429) was further stratified into subgroups based on exposure or no exposure to Glu/CS as follows: not exposed, 1 year, 2-3 years, and 4-6 years. Cartilage volume was assessed using fully automated quantitative MRI technology.The Jonckheere-Terpstra trend test indicated that treatment with Glu/CS significantly reduced the cartilage volume loss in the global knee, associated with the lateral compartment. Multivariate analysis further demonstrated that the extent of the treatment's positive effect was related to exposure time to treatment, the protective effect at 6 years being significant in participants exposed to ≥2 years of treatment.These findings provide future support for the long-term protective structure-modifying effects of Glu/CS treatment in knee OA subjects.

Objective Limited studies have explored the association between adipokines and knee OA structural progression using quantitative MRI (qMRI), and very few have included total knee replacement (TKR) as a disease outcome. The objective of this study was to compare serum levels of five adipokines to cartilage volume loss (CVL) and investigate their predictive value for TKR. Methods The according-to-protocol population (n = 138) of a knee OA trial was used. Serum levels of adipsin (complement factor D), leptin, adiponectin, resistin and serpin E1, and cartilage volume were determined at baseline and 24 months with specific ELISAs and qMRI, respectively. Study knee TKR incidence up to 4 years post-trial was also assessed. Results Greater baseline values of adipsin and leptin correlated with increased CVL in the global knee and medial femur (P ⩽ 0.032) and of adipsin in the lateral compartment and femur (P ⩽ 0.028). Adiponectin showed an inverse correlation in the medial compartment and femur (P ⩽ 0.027). Resistin and serpin E1 were not associated with CVL. Multivariate analyses revealed that patients in the highest tertile at baseline of adipsin presented a greater odds ratio of CVL in the lateral compartment and femur (⩾2.87; P ⩽ 0.011), and those in the highest tertile of leptin in the medial compartment (2.78; P = 0.038). Most clinically relevant, patients in the highest tertile of adipsin or leptin at baseline had significantly greater incidence of TKR (P = 0.027). Conclusion Data demonstrate that both adipsin and leptin predict greater CVL over time in the lateral and medial compartment, respectively. Importantly, this study also demonstrates that higher baseline levels of adipsin or leptin are associated with higher incidence of TKR.

Background Change in knee cartilage volume is frequently used as a proxy for change in knee joint space width over time, but longitudinal data on these associations is limited. We aimed to determine whether change in knee cartilage volume, new or worsening meniscal extrusion (ME), meniscal tears and cartilage defects over 2.4 years correlated with change in joint space width (JSW) over 5 years in older community dwelling adults. Methods Participants (n = 153) had their right knee imaged using MR imaging and x-ray at baseline, and after 2.4 years (MRI) and 5 years (x-ray). Cartilage volume, cartilage defects, meniscal extrusions and meniscal tears were assessed on sagittal T1-weighted fat-suppressed MRI. JSW was assessed using standard fixed semi-flexed view radiographs, and scored on those with adequate alignment. Results Participants were 51–79 (mean 62) years old; 48 % were female. Cartilage volume reduced over time (medial −134 ± 202 μL/year, lateral −106 ± 165 μL/year, p

We wish to address the comments by Felson1 regarding our recently published article . 2 This study used the osteoarthritis initiative (OAI) cohort database, which offers a unique opportunity to explore the onset and progression of knee osteoarthritis (OA) and the potential effects of treatments on the natural progression of the disease. Obviously, as does any observational study, such cohort has limitations. The rationale behind the referenced work was to build a study design that circumvented some of the limitations of the OAI cohort by selecting a subpopulation of the participants. We wanted to study, as reliably as possible, the potential disease-modifying osteoarthritis drug (DMOAD) effects of glucosamine (Glu) and chondroitin sulfate (CS) in a design that would mimic a randomised controlled trial (RCT) with all of the restrictions that such a study design could impose in the context of an observational study. From the first-line analysis it was obvious that the patient population was heterogeneous from a clinical standpoint, with one of the main factors being related to disease treatment (±analgesics/non-steroidal anti-inflammatory drugs (NSAIDs)) and the implicit severity of the disease based on symptoms and joint space width (JSW). This observation was interesting and, importantly, clinically relevant. As outlined in the study design section, we …

Methods: Symptomatic primary knee OA patients according to ACR criteria with KellgrenLawrence grades 2-3 and synovitis were included and treated with CS (1200 mg a day) or CE (200 mg once daily) for 24 months. Patients at high risk for cardiovascular and/or gastrointestinal disease were not included. MRI was performed at baseline, 12 and 24 months. CVL, bone marrow lesion (BML) size, and synovial membrane thickness were evaluated using qMRI, and presence of joint swelling and effusion clinically evaluated. Clinical symptoms were also assessed by validated questionnaires. Statistical analyses were done on the intention-to-treat (ITT) population (n=194 patients), per protocol set (n= 195) and the according-to-protocol completer population (n=120) using Student’s t-test, Wilcoxon MannWhitney test, and ANCOVA.

Introduction Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP). Methods This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed. Results Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P

Studies have proposed vastus medialis (VM) muscle cross-sectional area change as a variable associated with cartilage volume loss in knee osteoarthritis (OA). However, the VM also includes fat (%Fat), which may influence knee function. This study analyzed the VM area and %Fat data, separately and in combination, to predict symptoms, cartilage volume loss, and bone marrow lesion (BML) change in knee OA.This study included the according-to-protocol population (n = 143) of a 2-year knee OA randomized clinical trial having magnetic resonance imaging at baseline and 2 years. Correlations used multivariate analyses.Greater baseline value for VM area and %Fat were significantly associated with sex (male, area; female, %Fat), higher body mass index (BMI), and Western Ontario and McMaster Universities Osteoarthritis Index stiffness, function, and total scores (better, high area; worse, high %Fat). Moreover, a VM %Fat increase of 1% at 2 years was associated with worsening of cartilage volume loss in the global knee (P = 0.015) and some subregions (P ≤ 0.030), and with an increment of BML global score change (P0.001). A 1% decrease in VM area at 2 years was associated with worsening of knee pain score (P = 0.048). Importantly, the concurrent presence of low VM area, high VM %Fat, and high BMI identified a subgroup of patients with greater cartilage volume loss in the medial femur (P = 0.028) than the rest of the cohort.These data demonstrated, for the first time, that VM fat content is a strong predictor of cartilage volume loss and the occurrence and progression of BML. Importantly, the combined data of VM area, VM %Fat, and BMI identified patients at higher risk for OA progression.

Introduction To evaluate the impact of meniscal extrusion (Ext) on knee osteoarthritis (OA) structural progression and on response to strontium ranelate (SrRan) treatment at 36 months in patients with (+) or without (-) Ext, in association (+) or not (-) with bone marrow lesions (BML) in the medial compartment using X-rays (JSW) and qMRI. Methods Patients from the qMRI substudy of the SEKOIA trial (SrRan 1 g/day, n = 113; SrRan 2 g/day, n = 105; placebo, n = 112) were stratified based on whether meniscal extrusion and/or BML were present or not in the medial compartment. Results In the placebo group, Ext+ patients (n = 26) had more JSW loss (p = 0.002) and cartilage volume loss in the global knee (p = 0.034) and plateau (p = 0.005), and medial compartment (p = 0.0005) than Ext- patients (n = 86). Ext-BML+ patients (n = 18) demonstrated more JSW loss (p = 0.003) and cartilage volume loss in the global (p = 0.020) and medial femur (p = 0.055) than Ext-BML- (n = 68). Compared to Ext+ BML- (n = 14), Ext+ BML+ patients (n = 12) had more cartilage volume loss in the global femur (p = 0.028), with no change in JSW. The JSW loss (p = 0.0004) and cartilage volume loss (global knee, p = 0.033, medial compartment, p = 0.0005) were greater when Ext and BML were simultaneously present in the medial compartment. SrRan 2 g/day treatment demonstrated a reduction in OA knee structural progression with qMRI, but not with JSW, in which less cartilage volume loss was found in the plateaus (p = 0.007) in Ext+ patients (n = 15), and in the medial plateau (p = 0.046) in patients in whom both Ext and BML were co-localized. Conclusion The findings of this study are novel and could have an impact on future strategies regarding clinical trials. Indeed, data first argue for a combined, cumulative effect of meniscal extrusion and bone marrow lesions on cartilage loss and, secondly, they showed that SrRan may have protective effects in OA patients with meniscal extrusion as well as when both meniscal extrusion and BML are co-localized.

Objective To explore, using MRI, the disease-modifying effect of strontium ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions (BMLs) in a subset of patients from a Phase III clinical trial in knee osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)). Material and methods Patients with primary symptomatic knee OA were randomised to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee cartilage volume and BMLs. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results In this MRI subset, the distribution of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1 g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at baseline regarding demographics, clinical symptoms or imaging characteristics. Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12 (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than placebo. In patients with BML in the medial compartment at baseline, the BML score at 36 months was decreased in both treatment groups compared with the placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively), and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau compared with placebo. Conclusions In knee OA patients, treatment with SrRan 2 g/day was found to have beneficial effects on structural changes by significantly reducing CVL in the plateau and BML progression in the medial compartment.

Background The Osteoarthritis Initiative (OAI) is the largest knee osteoarthritis observational cohort. It provides the possibility to study the evolution of OA structural changes over time and the associated risk factors. It also allows the potential disease-modifying OA drug effects to be explored in patients over time. Objectives This study aimed to examine, for the first time, the long-term (6-year) protective effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on OA knee cartilage volume using the OAI cohort. Methods Participants from the OAI Progression and Incidence sub-cohorts who had MRI data on the target knee at baseline and at 6 years and with a JSW greater than 1 mm, and information on the Glu/CS consumption were included (n=1593). The participants were stratified into two main groups based on whether or not they had medial meniscal extrusion at baseline, and the former group (n=429) were further stratified into subgroups based on their exposure time: not exposed, 1 year, 2 to 3 years, and 4 to 6 years. MRI assessments were done using fully automated quantitative technologies1,2. Statistical analysis included the Jonckheere-Terpstra trend test as well as multivariate analysis test. Results Findings indicate that in participants with knee OA, treatment with the combined Glu/CS significantly reduced the loss of cartilage in the global knee associated with the lateral compartment. Moreover, the extent of the treatment9s positive effect was also found to be related to the exposure time to treatment, the protective effect at 6 years being significant in participants who were exposed to 2 or more years of treatment. Conclusions The findings of this study are in line with previous data showing chondroprotective effects of glucosamine and chondroitin sulfate treatment with preferential effects, and provide future support for the long-term structure-modifying effects of such treatment in knee osteoarthritis subjects. References Dodin P, Pelletier JP, Martel-Pelletier J, Abram F. IEEE Trans Biomed Eng. 2010;57:2699–711. Dodin P, Abram F, Pelletier JP, Martel-Pelletier J. J Biomed Graph Comput. 2013;3:51–65. Disclosure of Interest J. Marte-Pelletier Shareholder of: Arthrolab Inc., Grant/research support from: Bioiberica, Consultant for: Bioiberica, J. P. Raynauld: None declared, F. Abram: None declared, P. Delorme: None declared, J. P. Pelletier Shareholder of: Arthrolab Inc., Grant/research support from: Bioiberica, Consultant for: Bioiberica, Speakers bureau: Bioiberica

Background Whether meniscal extrusion and bone marrow lesions (BMLs) independently predict the risk of knee osteoarthritis (OA) remains to be clarified. Yet, while prospective cohort studies have shown that both meniscal extrusion and BMLs increase the risk of progressive knee OA, these studies have focused on the medial rather than the lateral knee joint, and examined people with established knee OA. It remains unclear whether these structural abnormalities predate incident knee OA, or whether meniscal extrusion or BMLs independently predict progressive disease. Objectives The aim of this 72 month longitudinal study was to examine whether compartmental baseline meniscal extrusion and BMLs were independently associated with incident and progressive knee OA, as measured by i) cartilage volume loss, ii) incident or progressive radiographic OA (ROA), and iii) total knee replacement (TKR). Methods Data was extracted from the Osteoarthritis Initiative (OAI) cohort. Participants were grouped according to the absence (Kellgren-Lawrence (KL) grade ≤1, n=2120) or presence (KL ≥2, n=2249) of ROA. Baseline meniscal extrusion, BMLs and cartilage volume were assessed on magnetic resonance imaging (MRI). Cartilage volume of the tibial plateau was assessed at baseline and 72 months, while ROA was assessed at baseline and 48 months. TKR was assessed at 72 months. Results In those with ROA, the presence of a baseline meniscal extrusion (independent of BMLs) was associated with accelerated cartilage loss (medial tibia: -2.1%/annum vs. -1.5%; lateral tibia: -2.6%/annum vs. -1.6%; both p Conclusions Baseline meniscal extrusion and BMLs predict incident and progressive knee OA and represent important and independent structural targets for patient selection in disease-modifying OA drug (DMOAD) trials. Disclosure of Interest J. Martel-Pelletier Shareholder of: ArthroLab Inc., A. Teichtahl: None declared, F. Cicuttini: None declared, F. Abram Employee of: ArthroLab Inc., Y. Wang: None declared, J.-P. Pelletier Shareholder of: ArthroLab Inc.

Background Although studies have predominantly focused on whether disease progression predicts symptoms in knee osteoarthritis (OA), there is very little data examining whether the presence of knee symptoms may be an independent predictor of the structural progression of knee OA. Objectives To complement and extend previous studies, we examined whether baseline and persistent knee symptoms predicted accelerated cartilage volume loss, incident and progressive radiographic OA (ROA) and total knee replacement (TKR). Methods Participants from the Osteoarthritis Initiative were grouped according to the absence (Kellgren-Lawrence [KL] grade ≤1, n=2120) or presence (KL ≥2, n=2249) of baseline ROA. Clinical symptoms (pain, stiffness and function) were assessed at baseline using Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Cartilage volume in the medial and lateral compartments was assessed by magnetic resonance imaging (MRI) at baseline and 48 months. Associations with incident and progressive ROA were assessed at 48 months and TKR at 72 months. Results Higher levels of baseline and persistent knee symptoms predicted greater annual percentage of cartilage loss in the medial (all p Conclusions Greater baseline and persistent knee symptoms predicted accelerated cartilage loss, incident and progressive ROA and TKR. Although a major focus in OA research has been the link between structural disease and symptom progression, data from this study demonstrate that symptoms are important independent predictors of disease progression. This suggests that targeting symptoms may be important for preserving joint structure. Disclosure of Interest J. Martel-Pelletier Shareholder of: ArthroLab Inc., A. Teichtahl: None declared, F. Cicuttini: None declared, Y. Wang: None declared, F. Abram Employee of: ArthroLab Inc., J.-P. Pelletier Shareholder of: ArthroLab Inc.

Background In osteoarthritis (OA) treatment, although chondroitin sulfate (CS) was found in a number of studies using radiography to have a structure modifying effect, to date the question is still under debate. A clinical study using quantitative magnetic resonance imaging (qMRI) is therefore of the utmost importance. Objectives The present study has the objective to explore, as the first aim, in a two-year randomized, controlled double-blind clinical study using qMRI, the disease modifying effect of CS treatment versus celecoxib (CE) on cartilage volume loss (CVL) in knee OA. The second aim was to investigate and compare the effect of CS and CE on symptoms. Methods Symptomatic primary knee OA patients according to ACR criteria with Kellgren-Lawrence grades 2–3 and synovitis were included and treated with CS (1200 mg a day) or CE (200 mg once daily) for 24 months. Patients at high risk for cardiovascular and/or gastrointestinal disease were not included. MRI was performed at baseline, 12 and 24 months. CVL, bone marrow lesion (BML) size, and synovial membrane thickness were evaluated using qMRI, and presence of joint swelling and effusion clinically evaluated. Clinical symptoms were also assessed by validated questionnaires. Results In the intention-to-treat analysis (n=194), patients treated with CS had reduced CVL at 24 months in the medial compartment (p=0.026) and condyle (p=0.008) compared to celecoxib. In the completer analysis, CS reduced CVL in the medial compartment at 12 months (p=0.026) and medial compartment and condyle at 24 months (p=0.030, p=0.010). A trend toward a reduced (p=0.070) synovial thickness in the medial suprapatellar bursa was observed in CS patients. Both treatment groups experienced a marked reduction in incidence of patients with joint swelling/effusion and in symptoms (WOMAC total, pain, and function, and VAS pain) over time. Data showed similar good safety profiles for both drug treatments. Conclusions This trial demonstrated, for the first time, the superiority of CS over CE at reducing the long term progression of knee OA structural changes. Moreover, both drugs were found equally effective at reducing the symptoms of OA. These findings have important implications regarding the usefulness of CS for long term management of knee OA and its impact on disease outcome. Disclosure of Interest J. P. Pelletier Shareholder of: Arthrolab Inc., Grant/research support from: Bioiberica, Consultant for: Bioiberica, Speakers bureau: Bioiberica, J. P. Raynauld: None declared, A. Beaulieu: None declared, L. Bessette: None declared, F. Morin: None declared, A. J. Brum-Fernandes: None declared, F. Abram: None declared, M. Dorais: None declared, J. Martel-Pelletier Shareholder of: Arthrolab Inc., Grant/research support from: Bioiberica, Consultant for: Bioiberica

Background/Objective: Bone marrow lesions (BMLs) have been associated with pain and cartilage degeneration in patients with knee osteoarthritis; their specific detection and quantification is therefore of primary importance. This study aimed at developing a fully automated quantitative BML assessment technology for human knee osteoarthritis using magnetic resonance images (MRI) and two sequences, a T1/T2*-weighted gradient echo (DESS) and a water-sensitive intermediate-weighted turbo spin echo (IW-TSE). Methods: The automated BML quantification first characterizes the bone and cartilage domains in the DESS sequence using our already published automated technology, then proceeds to the BML quantification which was developed as a four-stage process: selection of structured bright areas corresponding to BMLs, geometric filtering of unrelated structures, segmentation of the BML, and quantification of BML proportion within bone regions. For the IW-TSE sequence, the first step consists of the transfer of the bone and cartilage objects from the DESS to the IW-TSE images, followed by the BML detection and quantification as for the DESS. Validation was performed on 154 OA patients from a subset of the Osteoarthritis Initiative (OAI) cohort (public data sets) in which BML manual segmentation intra- and inter-reader reliability was done for each sequence (DESS and IW-TSE) using the intraclass correlation (ICC). BML comparison between the newly developed automated method with a manual segmentation was performed with ICC for the proportion of BML and Dice similarity coefficient (DSC) for BML localization and geometric extent. Finally, comparisons between the DESS and the IW-TSE sequences were performed for BML incidence and proportion. Results: Excellent to very good correlations were obtained for both MRI sequences for intra- and inter-reader reliability of the manual BML segmentation. Comparison between the developed automated method and the manual BML segment- ation showed excellent to very good correlations in the global knee and regions (ICC=0.99 to 0.68 for DESS and 0.99 to 0.77 for IW-TSE sequences) as well as very good to good similarity for the BML geometrical agreement (DESS, 0.60 to 0.41; IW-TSE, 0.59 to 0.41). Data revealed greater BML incidence at the sites of high articular constraints: lateral femoropatellar and medial tibiofemoral articulation. Average BML proportion revealed a scaling factor of about 4.5-fold more for the IW-TSE compared to the DESS. Conclusions: The newly developed fully automated MRI based BML assessment technology not only detects the absence/ presence of these pathological signals in the osteoarthritic human knee, but also provides accurate quantitative assessment of BMLs in the global knee and knee regions. Such automated system will enable large scale studies to be conducted within shorter durations, as well as increase stability of the reading.

Objective.To investigate over a 1-year period in dogs that underwent extracapsular stabilization surgery (ECS) following anterior cruciate ligament (ACL) transection: whether reconstructive surgery could prevent osteoarthritis (OA) progression and whether treatment with the bisphosphonate tiludronic acid (TA) could improve the chronic evolution of OA structural changes.Methods.ACL transection was performed on dogs on Day 0 and ECS on Day 28. Dogs were randomly divided into 2 groups: 15 received placebo and 16 were treated with TA (2 mg/kg subcutaneous injection) on Days 14, 28, 56, and 84. Magnetic resonance images were acquired on Days −10, 26, 91, 210, and 357, and cartilage volume was quantified. At sacrifice (Day 364), cartilage from femoral condyles and tibial plateaus was macroscopically and histologically evaluated. Expression levels of MMP-1, -3, -13, ADAMTS-4, -5, BMP-2, FGF-2, IGF-1, TGF-ß1, collagen type II, and aggrecan were determined using real-time RT-PCR.Results.The loss of cartilage volume observed after ACL transection stabilized following ECS. Thereafter, a gradual gain occurred, with the cartilage volume loss on the tibial plateaus reduced at Day 91 (p < 0.02) and Day 210 (p < 0.001) in the TA-treated dogs. At sacrifice, TA-treated dogs presented a reduction in the severity of macroscopic (p = 0.03 for plateaus) and histologic (p = 0.07 for plateaus) cartilage lesions, had a better preserved collagen network, and showed decreased MMP-13 (p = 0.04), MMP-1 and MMP-3 levels.Conclusion.Our findings indicate that in dogs with ACL transection, ECS greatly prevents development of cartilage volume loss. Treatment with TA provided an additional benefit of reducing the development of OA lesions.

Objectives. The presence of bone marrow lesions (BMLs) has been linked to pain and progression of knee OA. The aim of this study was to determine the relationship between BMLs and longitudinal change in tibial cartilage volume and risk of knee joint replacement in subjects with knee OA. Methods. One hundred and nine men and women with symptomatic knee OA were recruited. The same knee was imaged using MRI at baseline and 2 years later. Tibial cartilage volume and BMLs were measured. Knee joint replacement over 4 years was determined. Results. The mean age of the subjects at baseline was 63.2 (S.D. 10.3) years. BMLs were present in 66% of the subjects. Cross-sectionally, BMLs were negatively associated with both medial (regression coefficient 121.4; 95% CI 183.8, 859.1; P

This study aimed at developing a fully automated bone segmentation method for the human knee (femur and tibia) from magnetic resonance (MR) images. MR imaging was acquired on a whole body 1.5T scanner with a gradient echo fat suppressed sequence using an extremity coil. The method was based on the Ray Casting technique which relies on the decomposition of the MR images into multiple surface layers to localize the boundaries of the bones and several partial segmentation objects being automatically merged to obtain the final complete segmentation of the bones. Validation analyses were performed on 161 MR images from knee osteoarthritis patients, comparing the developed fully automated to a validated semi-automated segmentation method, using the average surface distance (ASD), volume correlation coefficient, and Dice similarity coefficient (DSC). For both femur and tibia, respectively, data showed excellent bone surface ASD (0.50 ± 0.12 mm; 0.37 ± 0.09 mm), average oriented distance between bone surfaces within the cartilage domain (0.02 ± 0.07 mm; −0.05 ± 0.10 mm), and bone volume DSC (0.94 ± 0.05; 0.92 ± 0.07). This newly developed fully automated bone segmentation method will enable large scale studies to be conducted within shorter time durations, as well as increase stability in the reading of pathological bone.

This study aimed at developing a new automatic segmentation algorithm for human knee cartilage volume quantification from MRI. Imaging was performed using a 3T scanner and a knee coil, and the exam consisted of a double echo steady state (DESS) sequence, which contrasts cartilage and soft tissues including the synovial fluid. The algorithm was developed on MRI 3-D images in which the bone-cartilage interface for the femur and tibia was segmented by an independent segmentation process, giving a parametric surface of the interface. First, the MR images are resampled in the neighborhood of the bone surface. Second, by using texture-analysis techniques optimized by filtering, the cartilage is discriminated as a bright and homogeneous tissue. This process of excluding soft tissues enables the detection of the external boundary of the cartilage. Third, a technology based on a Bayesian decision criterion enables the automatic separation of the cartilage and synovial fluid. Finally, the cartilage volume and changes in volume for an individual between visits was assessed using the developed technology. Validation included first, for nine knee osteoarthritis patients, a comparison of the cartilage volume and changes over time between the developed automatic system and a validated semi-automatic cartilage volume system, and second, for five knee osteoarthritis patients, a test-retest procedure. Data revealed excellent Pearson correlations and Dice similarity coefficients (DSC) for the global knee (r = 0.96 , p

Introduction Cartilage thickness and volume loss measurements using quantitative magnetic resonance imaging (qMRI) are suggested to detect significant cartilage changes over short time intervals. We aimed to compare these two different approaches looking at the global knee and subregions, using data from an osteoarthritis (OA) multicentre randomised clinical trial. Methods Three hundred and fifty-five patients with symptomatic knee OA were recruited for a two-year, double-blind, randomised clinical trial evaluating the effect of 200 mg licofelone twice daily and 500 mg naproxen twice daily on cartilage loss, and 301 patients had baseline MRI. MRIs were performed at baseline, 6, 12 and 24 months. Cartilage volume and thickness in the global joint, medial and lateral compartments, and central weight-bearing subregions of the medial and lateral femoral condyles and tibial plateaus were analysed. Data were analysed for the mean value imputed for intent-to-treat (ITT-MVI) and statistical analyses were performed using two-sample Student's t-test. Results Cartilage mean thickness loss in the global joint, lateral and medial compartments, as well as in medial compartments stratified according to patients with or without meniscal extrusion, was significantly less in the licofelone compared with the naproxen group at 12 and 24 months. Interestingly, these data were similar to those found when using cartilage volume loss as an outcome. Although greater cartilage volume and mean thickness loss was seen in central weight-bearing subregions of the medial and lateral compartments compared with the whole compartment and also in patients with meniscal lesions/extrusion, suggesting good sensitivity to change, its high standard deviation precluded for the condyles a high statistical power and abrogated statistically significant differences between the treatment groups. Conclusions These data demonstrate that both the measurement of cartilage thickness and that of cartilage volume provide the same level of sensitivity to estimate cartilage loss in a clinical trial. However, the potential of gaining statistical power with the use of thickness/volume change in knee subregions as an outcome seems negated by high inter-patient variability. Moreover, there is no superiority in statistical power by selecting patients with meniscal extrusion.

SummaryObjectivesSynovitis in knee osteoarthritis (OA) patients is a significant risk factor for disease progression. This study aimed at developing a magnetic resonance imaging (MRI) scoring system allowing reliable and sensitive assessment of synovitis severity in knee OA patients without the use of a contrast agent.MethodsImaging was performed without contrast agent, using a 1.5T and a knee coil. For the synovial membrane, the MRI exam included two axial sequences: a T2-weighted (synovial fluid) and a gradient echo (GRE) (synovial membrane). Synovial membrane thickness was measured on four regions of interest (ROI): medial and lateral recesses, and medial and lateral suprapatellar bursa, with each graded/scored from 0 to 3, for a maximum of 12. A validation study was performed on a cohort of 27 knee OA patients having MRI at baseline. A subset of 14 patients had an additional MRI acquisition and symptom assessment at Day 60. Evaluation of disease symptoms was done with Western Ontario and McMaster Universities OA Index and visual analog scale, and of cartilage volume, menisci and subchondral bone, with MR images from a 3D spoiled gradient recalled (SPGR) sequence.ResultsThe synovial membrane thickness grade was 1.9±0.5 (mean±SD) with a score of 7.1±2.3. The intra-reader (r=0.91) and inter-reader (r=0.82) correlation coefficients were excellent (P

Assessment of structural damage of the articular cartilage is important for monitoring the progression of osteoarthritis (OA) and evaluating therapeutic response. For many years, clinical studies of drug interventions on symptomatic knee OA have focused mainly on clinical parameters, such as pain and joint function, using self-administered questionnaires but without assessing the effect of treatment on structural changes caused by the disease and the role of treatment in preventing cartilage degradation. Recently, such attempts were made to evaluate cartilage damage and its progression in OA. Serial radiographs of affected joints have appeared as a logical means of documenting the progression of OA over time, providing that a validated, reliable, and easily reproducible technique is used [1]. Improvements in the standardization and interpretation of radiographs have enhanced the reliability of the measurement of the joint space width (JSW) and the evaluation of the joint space narrowing (JSN) [2, 3]. However, the sensitivity to change of this measurement is such that a minimum follow-up of 2 to 3 years and more and large numbers of patients (at least 1500 for a two-arm study) is necessary to establish an effect of pharmacological interventions on OA progression. Moreover, measurement of JSW does not capture information on the cartilage changes alone but is also dependent on the integrity of surrounding tissues, especially the meniscus and the subchondral bone. For instance, enucleation of the knee medial meniscus, which may occur during longitudinal studies, can dramatically change the JSW and affect the reliability of such measurement [4], potentially impairing its use in the assessment of cartilage degradation over time. Finally, the JSW progression provides only one measurement

Objective— To compare use of 1.5 T magnetic resonance imaging (MRI) and computed radiography (CR) for morphologic and temporal evaluation of osteophytosis, subchondral sclerosis, joint effusion, and synovial thickening in experimentally induced canine stifle osteoarthritis (OA). Study Design— Prospective study. Animals— Dogs (n=8). Methods— CR (mediolateral and caudocranial projections) and MRI (dorsal 3D T1-weighted gradient echo, sagittal 3D SPGR and T2-weighted fast spin echo with fat saturation) were performed at baseline (n=8) and at week 4 (n=5), week 8 (n=8), and week 26 (n=5) after cranial cruciate ligament transection. Osteophytosis, subchondral bone sclerosis, and joint effusion were scored on CR and MRI, and synovial thickening on MRI. Results— MRI was more sensitive than CR for detection of osteophytosis and could better discriminate joint effusion from soft tissue thickening, although scores for these variables strongly correlated between modalities (ρ=0.94 [osteophytosis] and 0.80 [effusion]; P

To examine the associations between meniscal tear, knee structure, osteoarthritis (OA) risk factors, radiographic change, and symptoms in a largely non-osteoarthritic cohort.This cross-sectional study included 294 subjects with mean age 47 (SD 6) years, body mass index (BMI) 28 (SD 5), and 58% were female. Meniscal tear, knee cartilage defect score, quantitative tibial and femoral cartilage volume, and tibial plateau bone area were determined using T1-weighted fat saturated magnetic resonance images.In multivariable analysis, prevalence of meniscal tear was significantly associated with age (OR 1.06 to 1.12/year, all p0.05), BMI (OR 1.06 to 1.11/kg/m(2), all p0.05 with the exception of the lateral anterior horn), sex (women vs men: OR 4.14 to 4.23, p0.01 at the medial and lateral meniscal body site), and family history of OA (OR 1.97 to 2.01, p0.05 at the lateral meniscal anterior and posterior horns). Meniscal tear was associated with a higher tibiofemoral cartilage defect score at lateral body and all medial sites, lower tibial and femoral cartilage volume at the lateral compartment, markedly higher prevalent radiographic OA at medial compartment, and greater tibial bone area. Moreover, meniscal tear at the lateral posterior and anterior horns was significantly associated with WOMAC pain, stiffness, and function scores.Meniscal tear at specific sites shares risk factors with knee OA. Importantly, meniscal tear is associated with cartilage defect, loss of cartilage volume, alteration in bone size, and prevalence of radiographic OA, suggesting that meniscal tear in non-OA subjects appears to be an early event in the disease process, and may be a risk factor for knee cartilage damage and articular structural changes.

Background Some adipokines have been associated with osteoarthritis (OA) incidence and potentially its progression. Only a few studies have looked at their association with, and prediction of, structural progression of knee OA using quantitative MRI. Objectives This study contrasted serum levels of 5 adipokines to the changes in cartilage volume and examined if they could predict the occurrence of a total knee replacement (TKR). Methods This post hoc analysis was performed on the ATP population (n=138) of a knee OA randomized clinical trial 1,2. The serum levels of the obesity factors Adipsin/Complement Factor D (CFD), Leptin (LEP), Adiponectin (ADIPOQ), Resistin (RETN), and Serpin E1 (SERPINE1) as well as the cartilage volume were determined at baseline and at 24 month follow-up. TKR incidence of the study knee up to 4 years post trial completion was also evaluated. Univariate and multivariate analyses controlling for age, gender, BMI, and treatment allocation were performed. Results Higher baseline BMI was associated with greater baseline CFD and LEP levels (p≤0.006) and lower baseline ADIPOQ levels (p Conclusions These data demonstrate that both CFD and LEP predict greater cartilage volume loss over time in the lateral femur and medial compartment, respectively. Baseline “at risk” levels of LEP, CFD and ADIPOQ are associated with a greater occurrence of TKR. These findings add further insight to the role of adipokines in knee OA structural progression and outcome. References Raynauld JP et al. Ann Rheum Dis. 2009;68:938-47. Raynauld JP et al. Ann Rheum Dis. 2011;70:1382-8. Acknowledgements *Equal participation in the study Disclosure of Interest None declared

Background Knee osteoarthritis (OA) structural changes are complex and comprise cartilage volume loss as well as meniscal lesions, which were shown to promote cartilage loss. Recently, strontium ranelate (SrRan) was demonstrated to have DMOAD properties (1,2) . Objectives We thus further evaluated the role of meniscal extrusion (mExt) on knee OA progression and its impact on response to SrRan treatment assessed by X-rays (change in joint space width [JSW]) and qMRI (cartilage volume loss [CVL] in the medial compartment) at 36 months (M36) in subjects with (mExt+) or without (mExt) meniscal extrusion, in association (+) or not (-) with bone marrow lesions (BML). Methods Patients from the qMRI substudy of the SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA) (modified intention-to-treat, n=330) were stratified based on whether mExt (mExt+, n=60; mExt-, n=270) and BML were present or not (BML+, n=84; BML-, n=246) and on their association in the medial compartment at baseline. CVL was assessed by qMRI and JSW by X-rays at baseline and M36. Results In the placebo group, mExt+ patients demonstrated significantly more JSW loss (-0.76±0.67 mm; p=0.002) and CVL in the medial compartment (-10.40±4.23%; p=0.0005) than mExt- patients (-0.35±0.61 mm and -7.60±4.63%, respectively). mExt-/BML+ patients (n=18) had significantly more JSW loss (-0.77±0.68 mm; p=0.003) and a trend (-9.57±5.29%; p=0.090) toward more CVL compared to mExt-/BML- patients (n=68) (-0.23±0.55 mm and -7.08±4.33%, respectively). mExt+/BML+ patients (n=12) had a trend toward more CVL in the medial compartment (-11.22±1.90%; p=0.103) than mExt+/BML- (n=14) (-9.69±5.50%), while JSW change showed no difference. Importantly, the JSW loss and CVL in the medial compartment were greater when mExt and BML were both present simultaneously in this compartment. In mExt+ patients, while no difference was found in the JSW loss between groups, SrRan at 2 g/day reduced the CVL in the plateaus (-5.74±3.54%; p=0.007) and a trend toward a decrease in the medial plateaus (-4.90±5.19%; p=0.081) compared to the placebo (-10.01±5.79% and -9.07±8.74% respectively). In the mExt+/BML+ patients, SrRan 2 g/day significantly reduced the CVL in the medial plateaus (-1.13±2.24% vs -11.45±4.47% for the placebo; p=0.046), whereas there was no difference for the JSW loss. Conclusions The progression of knee OA assessed both by X-rays and qMRI was greater in mExt+ patients, and was further increased when co-localized with BML. Based on qMRI, SrRan 2 g/day showed beneficial DMOAD structural effects in mExt+ and mExt+/BML+ patients, targeting a subpopulation at higher risk of knee OA progression, while JSW loss was not sensitive enough to provide evidence of such effects. References Reginster JY. et al. Ann Rheum Dis 2013;72:179-86. Pelletier JP et al. Ann Rheum Dis. 2013 Dec 2. doi: 10.1136/annrheumdis-2013-203989. Disclosure of Interest C. Roubille: None declared, J. Martel-Pelletier Shareholder of: ArthroLab Inc., F. Abram Employee of: ArthroLab Inc., M. Dorais Consultant for: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J.-P. Pelletier Shareholder of: ArthroLab Inc. DOI 10.1136/annrheumdis-2014-eular.2539

Background The Osteoarthritis Initiative (OAI) is the largest knee osteoarthritis (OA) observational cohort. It provides the possibility to study the evolution of OA structural changes over time and the associated risk factors. It also allows the potential disease-modifying OA drug (DMOAD) effects to be explored in patients over time. Objectives To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of existing meniscal extrusion on the extent of cartilage loss and structural changes over time, and response to pharmacological treatment including the combination of glucosamine and chondroitin sulfate (Glu/CS). Methods Knee OA patients were stratified based on the presence/absence of medial meniscal extrusion at baseline and on whether or not they received conventional OA pharmacological treatment (analgesics/non-steroidal anti-inflammatory drugs [NSAIDs]) and/or Glu/CS for 24 consecutive months. The main outcomes were knee structural changes including the cartilage volume measured by quantitative magnetic resonance imaging (MRI) and of loss of joint space width (JSW). Results Participants reported taking (+) (n=300) or not taking (−) (n=300) OA treatment (analgesics/NSAIDs). The participants with meniscal extrusion had more severe disease at baseline. In the −analgesics/NSAIDs group with meniscal extrusion, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial tibiofemoral compartment (p=0.02) and lateral plateau (p=0.05). No effect of Glu/CS was observed in patients without extrusion. In the +analgesic/NSAIDs group without meniscal extrusion, those taking Glu/CS had significantly reduced loss of cartilage volume in the global knee (p=0.055), medial compartment (p=0.05), lateral plateau (p=0.007), and trochlea (p=0.04). No effect of Glu/CS treatment occurred in participants with extrusion. No significant reduction in JSW was found between those taking (+) and not taking (−) Glu/CS treatment. Conclusions This study confirms that combined administration of Glu/CS has significant protective effects on structure in knee OA. The presence of meniscal extrusion was found to be an important factor that can influence the drug effect on cartilage volume. X-rays were found to be much less sensitive than MRI at documenting the protective effect of treatment on structural changes. Disclosure of Interest : J.-P. Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica, C. Roubille: None declared, F. Abram Employee of: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J. Martel-Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica DOI 10.1136/annrheumdis-2014-eular.2248

Background Recent osteoarthritis (OA) studies propose vastus medialis (VM) muscle surface as a variable associated with cartilage volume loss over time. However, such muscle area may also include a significant proportion of fatty infiltration which may influence the knee mechanics/metabolism. Objectives We contrasted the muscle fatty infiltration with cartilage volume loss and changes in bone marrow lesions (BMLs) assessed by MRI using data from a recent randomized clinical trial in knee OA 1 . Methods A subgroup of 143 patients from the according-to-protocol population of a 2-year randomized clinical trial evaluating the impact of licofelone vs. naproxen and having MRI acquisitions at baseline and 2 years were studied. MR images of the VM (mm 2 ) were evaluated semi-automatically and VM percentage of fatty infiltration (%Fat) by a fully automated software. Univariate and multivariate analyses were performed to assess the relationship between VM area and its %Fat, cartilage volume loss, and BML change over 2 years. Results The average %Fat/VM surface area was 6.3±3.9%. In the VM, the median baseline %Fat (5.1%) was chosen to separate patients with high vs. low fat content. Female (p=0.004) and higher BMI (33.2±5.7 vs. 30.2±5.3, p=0.001) and disability (WOMAC function 59±18 vs. 53±15, p=0.04) were associated with a higher %Fat. Change at 2 years in %Fat was univariately strongly associated with an increase in the BML score in the global knee (p=0.0002) and cartilage volume loss in the global knee (p=0.01), lateral compartment (p=0.02), plateau (p=0.01), and medial plateau (p=0.03). No correlations were found between %Fat change and change in symptoms over time. Multivariate analyses correcting for age, gender, BMI, and meniscal damage revealed correlations with %Fat for the global knee (p=0.011), plateau (p=0.012), and medial plateau (p=0.019) and condyle (p=0.027). Importantly, %Fat change was independently and strongly associated with BML change (p Conclusions These data demonstrated, for the first time, that the %Fat in the VM was strongly associated with cartilage volume loss and the occurrence and progression of BMLs References Raynauld JP, et al. Ann Rheum Dis 2009;68:938-47. Disclosure of Interest : J.-P. Raynauld Consultant for: ArthroLab Inc., J.-P. Pelletier Shareholder of: ArthroLab Inc., F. Abram Employee of: ArthroLab Inc., M. Dorais Consultant for: ArthroLab Inc., Y. Wang: None declared, J. Fairley: None declared, F. Cicuttini: None declared, J. Martel-Pelletier Shareholder of: ArthroLab Inc. DOI 10.1136/annrheumdis-2014-eular.2369

Objectives To explore using quantitative magnetic resonance imaging (qMRI) the disease modifying effect of strontium ranelate (SrRan) treatment on the cartilage volume loss and bone marrow lesions (BMLs) in a subgroup of patients from a Phase III clinical trial on human knee osteoarthritis (OA) (SEKOIA). Methods Patients with primary symptomatic knee OA were randomized to receive either SrRan 1 g or 2 g/day or placebo. MRI was performed at baseline, 12, 24, and 36 months. The changes in knee cartilage volume loss and BMLs were assessed in the global joint and subregions. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results In the subgroup of patients with MRI, the distribution of patients (n=330) was 113, 105, and 112 for SrRan 1 g/day, 2 g/day, and placebo, respectively. There were no between-group differences at baseline with regard to demographics, clinical symptoms, or imaging characteristics. Treatment with SrRan at 2 g/day significantly decreased the loss of cartilage volume on the tibial plateau at 12 (p=0.002) and 36 months (M36) (p=0.003). At M36, in patients with BML at baseline, the BML score decreased in the two treatment groups compared to an increase in the placebo group in the medial compartment (p=0.002 and p=0.001 in the SrRan 1 g/day and 2 g/day groups, respectively). In those patients, SrRan 2 g/day significantly (p=0.023) decreased the cartilage loss at M36 in the medial tibial plateau compared to placebo, whereas SrRan 1 g/day did not (p=0.763). Conclusions In knee OA patients, treatment with SrRan 2 g/day was found to have a beneficial effect both on cartilage and subchondral bone by significantly reducing the cartilage volume loss in the tibial plateau and the progression of BML in the medial compartment. Disclosure of Interest J. Martel-Pelletier Shareholder of: ArthroLab Inc, Grant/research support from: Servier, Consultant for: Servier, ArthroLab Inc, C. Roubille: None Declared, J.-P. Raynauld Consultant for: ArthroLab Inc, F. Abram Employee of: ArthroLab Inc., M. Dorais: None Declared, P. Delorme: None Declared, J.-P. Pelletier Shareholder of: ArthroLab Inc, Grant/research support from: Servier, Consultant for: Servier, ArthroLab Inc

Background The guidelines from the regulatory agencies require that joint structure modification also translate into a significant clinical benefit for the patient before allowing the claim of DMOAD (1). To this end, the prevention of patient disability and of the need for joint replacement has been suggested as possible clinically relevant outcomes (2). Objectives To predict from clinical trial and MRI data the incidence of total knee replacement (TKR) during the long-term follow-up of knee osteoarthritis (OA) patients who formerly received chondroitin sulfate (CS) or placebo. Methods Symptomatic knee OA patients participating in a previous 6-month randomized, double-blind controlled trial evaluating the impact of CS (Condrosan®, Bioiberica S.A., Barcelona, Spain) (800 mg/day) vs. placebo, with subsequent 6-month extension with all patients on CS, were contacted to evaluate retrospectively the incidence of TKR of the study knee. A sub-group of patients (n=51) belonging to the according-to-protocol cohort were selected for this post-hoc retrospective analysis. The TKR incidence was assessed with a standardized phone interview. Results The patients’ mean age was 62.9 years, 61% were female and the average body mass index was 30.6 kg$/$m 2 . A total of 13.7% TKRs were performed upon this sub-population in the time frame of 4 years after patient enrolment. More TKRs were performed within the placebo (71%) than the CS group (29%) (p=0.150, logistic regression). The baseline values of WOMAC pain (p=0.019, logistic regression), stiffness (p=0.013) and function (p=0.044), bone marrow lesions of the medial compartment (p=0.030), and C-reactive protein (CRP) levels (p=0.040) were strong predictors of TKR. Changes at 1 year in the medial cartilage volume (p=0.046) also predicted the occurrence of TKR. Conclusions In a knee OA clinical trial, it is possible to predict a “hard” outcome such as TKR using information from clinical and MRI data. The results also support the use of MRI as a surrogate for joint tissue damage upon which a DMOAD such as CS may act. References Guidance for the Industry. Clinical Development Programs for Drugs, Devices and Biological Products Intended for the Treatment Osteoarthritis. US Department of Health and Human Services. Food and Drug Administration, Center for Drug Evaluation and Research, July 1999. Altman RD et al. Osteoarthritis Cartilage 2005;13:13-9. Disclosure of Interest None Declared

Objectives To explore the effects of commonly used medications for treatment of knee osteoarthritis (OA) on structural progression. Methods Participants (n=600) were selected from the Osteoarthritis Initiative (OAI) progression cohort (http://www.oai.ucsf.edu/) (n=1,390) who met the following criteria: 24 consecutive months of follow-up with clinical and imaging data including radiographs and magnetic resonance imaging (MRI) of the index (highest WOMAC pain) knee. Data for joint space width (JSW) were obtained from the OAI database and cartilage volume was measured using fully-automated MRI. Results Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAID) over 24 months, with or without glucosamine and chondroitin sulfate (Glu/CS). The +analgesic/NSAID subjects had higher WOMAC scores (p Conclusions In both the +analgesic/NSAID and -analgesic/NSAID groups, participants who took Glu/CS had reduced loss of JSW and cartilage volume over 24 months. These effects of Glu/CS on structural changes support results from previous studies. Disclosure of Interest None Declared

Introduction Recent evidence suggests that bone marrow lesions (BMLs) play a pivotal role in knee osteoarthritis (OA). The aims of this study were to determine: 1) whether baseline BML presence and/or severity predict site-specific cartilage defect progression and cartilage volume loss; and 2) whether baseline cartilage defects predict site-specific BML progression. Methods A total of 405 subjects (mean age 63 years, range 52 to 79) were measured at baseline and approximately 2.7 years later. Magnetic resonance imaging (MRI) of the right knee was performed to measure knee cartilage volume, cartilage defects (0 to 4), and BMLs (0 to 3) at the medial tibial (MT), medial femoral (MF), lateral tibial (LT), and lateral femoral (LF) sites. Logistic regression and generalized estimating equations were used to examine the relationship between BMLs and cartilage defects and cartilage volume loss. Results At all four sites, baseline BML presence predicted defect progression (odds ratio (OR) 2.4 to 6.4, all P < 0.05), and cartilage volume loss (-0.9 to -2.9% difference per annum, all P < 0.05) at the same site. In multivariable analysis, there was a significant relationship between BML severity and defect progression at all four sites (OR 1.8 to 3.2, all P < 0.05) and BML severity and cartilage volume loss at the MF, LT, and LF sites (β -22.1 to -42.0, all P < 0.05). Additionally, baseline defect severity predicted BML progression at the MT and LF sites (OR 3.3 to 3.7, all P < 0.01). Lastly, there was a greater increase in cartilage volume loss at the MT and LT sites when both larger defects and BMLs were present at baseline (all P < 0.05). Conclusions Baseline BMLs predicted site-specific defect progression and cartilage volume loss in a dose-response manner suggesting BMLs may have a local effect on cartilage homeostasis. Baseline defects predicted site-specific BML progression, which may represent increased bone loading adjacent to defects. These results suggest BMLs and defects are interconnected and play key roles in knee cartilage volume loss; thus, both should be considered targets for intervention.

Introduction Joint effusion is frequently associated with osteoarthritis (OA) flare-up and is an important marker of therapeutic response. This study aimed at developing and validating a fully automated system based on magnetic resonance imaging (MRI) for the quantification of joint effusion volume in knee OA patients. Methods MRI examinations consisted of two axial sequences: a T2-weighted true fast imaging with steady-state precession and a T1-weighted gradient echo. An automated joint effusion volume quantification system using MRI was developed and validated (a) with calibrated phantoms (cylinder and sphere) and effusion from knee OA patients; (b) with assessment by manual quantification; and (c) by direct aspiration. Twenty-five knee OA patients with joint effusion were included in the study. Results The automated joint effusion volume quantification was developed as a four stage sequencing process: bone segmentation, filtering of unrelated structures, segmentation of joint effusion, and subvoxel volume calculation. Validation experiments revealed excellent coefficients of variation with the calibrated cylinder (1.4%) and sphere (0.8%) phantoms. Comparison of the OA knee joint effusion volume assessed by the developed automated system and by manual quantification was also excellent (r = 0.98; P < 0.0001), as was the comparison with direct aspiration (r = 0.88; P = 0.0008). Conclusions The newly developed fully automated MRI-based system provided precise quantification of OA knee joint effusion volume with excellent correlation with data from phantoms, a manual system, and joint aspiration. Such an automated system will be instrumental in improving the reproducibility/reliability of the evaluation of this marker in clinical application.