Research article

Analysis of the precision and sensitivity to change of different approaches to assess cartilage loss by quantitative MRI in a longitudinal multicentre clinical trial in patients with knee osteoarthritis

Jean-Pierre Raynauld¹ , Johanne Martel-Pelletier¹ , François Abram² , Marc Dorais³ , Boulos Haraoui¹ , Denis Choquette¹ , Peter Bias⁴ , Karl H Emmert⁴ , Stefan Laufer⁵ and Jean-Pierre Pelletier¹

¹  Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec, H2L 4M1, Canada

²  ArthroVision Inc., 1871 Sherbrooke Street East, Montreal, Quebec, H2K 1B6, Canada

³  Research Group in Pharmacoepidemiology and Pharmacoeconomics, Research Centre, University of Montreal Hospital Centre, Hôtel-Dieu Hospital, 3850 rue Saint-Urbain, Montreal, Quebec, H2W 1T8, Canada

⁴  Clinical Research, Merckle GmbH, chem.-pharm. Fabrik, Graf-Arco-Strasse 3, Postfach 1780 Ulm-Donautal D-89079, Germany

⁵  Department of Pharmaceutical Chemistry/Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf Der Morgenstelle 8, Tübingen D-72074, Germany

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R129doi:10.1186/ar2543

Published:	5 November 2008

Abstract

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.