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Tanamas S.K.,Monash University | Wluka A.E.,Monash University | Pelletier J.-P.,University of Montreal | Pelletier J.M.,University of Montreal | And 5 more authors.
Rheumatology | Year: 2010

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 < 0.001) and lateral (regression coefficient -142.1; 95% CI -241.8, -42.4; P = 0.01) tibial cartilage volume data. Longitudinally, for every 1-score increase in baseline BML severity (range 0-4), the annual total tibial cartilage loss was increased by 1.14% (95% CI 0.29%, 1.87%; P = 0.01). The risk of knee joint replacement over 4 years increased with increasing BML score (odds ratio 1.57; 95% CI 1.04, 2.35; P = 0.03). Conclusion. The prevalence and severity of BMLs are associated with less tibial cartilage volume and greater cartilage loss over 2 years. Moreover, severity of BMLs was positively associated with risk of knee joint replacement over 4 years. This provides further support for the importance of BMLs in identifying those with OA most likely to progress. Identifying factors that prevent or reduce the severity of BMLs may provide an important target in the prevention of disease progression and treatment of OA, and the subsequent need for arthroplasty. © The Author 2010. All rights reserved. Source

Wildi L.M.,University of Montreal | Raynauld J.-P.,University of Montreal | Martel-Pelletier J.,University of Montreal | Beaulieu A.,Laval University | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective To determine the effect of chondroitin sulphate (CS) treatment on cartilage volume loss, subchondral bone marrow lesions (BML), synovitis and disease symptoms in patients with knee osteoarthritis (OA). Methods In this pilot multicentre, randomised, doubleblind, controlled trial in primary knee OA, 69 patients with clinical signs of synovitis were randomised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily. Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months; synovial membrane thickness was assessed at baseline and at 6 months. Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee (p=0.030), lateral compartment (p=0.015) and tibial plateaus (p=0.002), with significance persisting at 12 months. Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment (p=0.035) and the lateral femoral condyle (p=0.044). Disease symptoms were similar between the two groups. Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment, and BML at 12 months. These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA. Source

Wei S.,Menzies Research Institute | Venn A.,Menzies Research Institute | Ding C.,Menzies Research Institute | Martel-Pelletier J.,University of Montreal | And 4 more authors.
Osteoarthritis and Cartilage | Year: 2011

Objective: Sex hormones and reproductive factors may be important for osteoarthritis (OA). The aim of this study was to describe the associations of parity, use of hormone replacement therapy (HRT) and oral contraceptives (OCs) with cartilage volume, cartilage defects and radiographic OA in a population-based sample of older women. Design: Cross-sectional study of 489 women aged 50-80. years. Parity, use of HRT and OC was assessed by questionnaire; knee cartilage volume and defects by magnetic resonance imaging and knee joint space narrowing (JSN) and osteophytes by X-ray. Results: Parity was associated with a deficit in total knee cartilage volume [adjusted β= -0.69. ml, 95% confidence interval (CI) -1.34, -0.04]. Increasing parity was associated with decreasing cartilage volume in both the tibial compartment and total knee (both P trend <0.05). Parity was also associated with greater cartilage defects in the patella compartment [adjusted odds ratio (OR) = 2.87, 95% CI = 1.39, 5.93] but not other sites. There was a consistent but non-significant increase in knee JSN (OR = 2.78, 95% CI = 0.75, 10.31) and osteophytes (OR = 1.69, 95% CI = 0.59, 4.82) for parous women. Use of HRT and/or OC was not associated with cartilage volume, cartilage defects or radiographic change. Conclusions: Parity (but not use of HRT or OC) is independently associated with lower cartilage volume primarily in the tibial compartment and higher cartilage defects in the patella compartment in this population-based sample of older women. © 2011 Osteoarthritis Research Society International. Source

Wildi L.M.,University of Montreal | Raynauld J.-P.,University of Montreal | Martel-Pelletier J.,University of Montreal | Abram F.,ArthroVision Inc. | And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objective: To assess in a multicentre randomised double-blind phase III clinical trial evaluating the effect of licofelone in comparison with naproxen on knee osteoarthritis (OA) the presence of, and change in, bone marrow lesions (BML) over time, their relationship to cartilage volume loss, meniscal extrusion and pain. Methods: Patients with knee OA were selected from the dataset of a recently published randomised controlled trial. MRI was performed at baseline, 6, 12 and 24 months to assess BML score (modified Whole-Organ MRI Score) and cartilage volume changes over time. Pain levels were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Results: One hundred and sixty-one patients completed the study according to protocol. The global knee and all subregions showed increased BML scores over time (p <0.001, 24 months) except for the medial tibial plateau in the licofelone group. In multivariate regression analysis, licofelone treatment predicted reduction in BML score in the medial tibial plateau (β= -0.280, p = 0.026). BML scores at baseline correlated with cartilage volume over time; however, correlation was limited to 12 months. No positive correlation was found between BML and WOMAC scores. Conclusions: BML scores were found to increase over time, probably owing to accumulation of chronic structural changes. Correlation between BML and cartilage volume was strong at baseline but not over time, probably due to the study drug. Licofelone reduced the BML score in the medial tibial plateau. In contrast to previous reports, no positive relationship was found between BML score (baseline or change over time) and pain, probably an effect of the selected population. Source

Raynauld J.-P.,University of Montreal | Martel-Pelletier J.,University of Montreal | Beaulieu A.,Laval University | Bessette L.,Groupe de Recherche en Rhumatologie et Maladies Osseuses | And 4 more authors.
Seminars in Arthritis and Rheumatism | Year: 2010

Objectives: The aim of the study was to evaluate by quantitative magnetic resonance imaging the effect of celecoxib 200 mg daily on cartilage volume loss over 12 months in knee osteoarthritis. Methods: The primary outcome of this study was to evaluate cartilage volume loss in the medial compartment of the knee (femoral condyle and tibial plateau) assessed by quantitative magnetic resonance imaging on subjects receiving continuous treatment with celecoxib 200 mg daily for 12 months compared with a modelized historical control cohort, as expressed by the percentage loss from baseline. Safety of the medication was also assessed. Comparison of the observed volume loss to the expected loss was evaluated by a multivariate linear regression model based on a historical cohort. Results: For the primary outcome, the 95% confidence intervals for the mean observed celecoxib cohort joint medial compartment cartilage volume loss (6.81% [6.01; 7.60]) and mean predicted loss (modelized historical cohort) (5.65% [5.10; 6.19]) overlap, indicating no significant difference and hence no effect of celecoxib on the medial compartment cartilage volume loss. Similar findings were demonstrated for the lateral compartment cartilage loss. The safety data reported several minor adverse events similar to those typically seen in a 1-year clinical trial. Conclusions: Although celecoxib was demonstrated to be safe for knee osteoarthritis at a 200 mg daily dose, it did not provide a protective effect on knee cartilage loss. Cohort modelization is an efficient and unbiased way to provide a comparator group for the assessment of novel treatments when classic head-to-head randomized controlled trials are not feasible. © 2010 Elsevier Inc. Source

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