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Hall J.,University of Tasmania | Laslett L.L.,University of Tasmania | Martel-Pelletier J.,University of Montreal | Pelletier J.-P.,University of Montreal | And 6 more authors.
BMC Musculoskeletal Disorders | Year: 2016

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 < 0.001), as did JSW (medial -0.05 ± 0.16 mm/year, lateral -0.12 ± 0.24 mm/year, p < 0.001). In multivariable analysis, the only consistent predictor of change in JSW was new or worsening ME (medial tibia R2 3.1 %, p = 0.031; medial femur R2 3.2 %, p = 0.024); change in cartilage volume correlated with change in JSW laterally (R2 4.8 %, p = 0.007) and was borderline medially (R2 2.2 %, p = 0.064); there was no association for meniscal tears or cartilage defects. The magnitude of these associations were similar albeit somewhat greater for ME in participants with radiographic OA (R2 6.2 %, p = 0.017). Conclusion: Change in ME and cartilage volume weakly predict change in JSW, but the vast majority of the variation remains unexplained. Since MRI examines cartilage directly while radiographs examine it indirectly, these results cast doubt on the validity of using JSW as a proxy measure of cartilage loss. © 2016 Hall et al. Source


Martel-Pelletier J.,University of Montreal | Raynauld J.-P.,University of Montreal | Dorais M.,StatSciences Inc. | Abram F.,ArthroLab Inc. | Pelletier J.-P.,University of Montreal
Rheumatology (United Kingdom) | Year: 2016

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. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Source


Pelletier J.-P.,University of Montreal | Roubille C.,University of Montreal | Raynauld J.-P.,University of Montreal | Abram F.,ArthroLab Inc. | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2013

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. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism. Source


Martel-Pelletier J.,University of Montreal | Roubille C.,University of Montreal | Abram F.,ArthroLab Inc. | Hochberg M.C.,University of Maryland, Baltimore | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes. Methods: Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI. Results: Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p<0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSW≤median). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSW>median). By contrast, no significant reduction in JSW was found between all groups. Conclusions: In +analgesic/NSAIDs groups and -analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism. Source


Pelletier J.-P.,University of Montreal | Troncy E.,Quebec Animal Pharmacology Research Group | Troncy E.,University of Montreal | Bertaim T.,Clinical Exploration | And 9 more authors.
Journal of Rheumatology | Year: 2011

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. Source

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