Objective Knee osteoarthritis commonly requires joint replacement, substantially reduces quality of life and increases healthcare utilisation and costs. This study aimed to identify whether quantitative measures of articular cartilage structure predict knee replacement, and to establish their utility as outcomes in clinical trials of disease-modifying therapy.
Methods A nested case–control study was performed in Osteoarthritis Initiative participants, a multicentre observational cohort of 4796 participants with or at risk of knee osteoarthritis. 127 knees were replaced between baseline and 4 years follow-up, and one control knee per case matched for baseline radiographic disease stage (Kellgren–Lawrence grade; KLG), gender and age. Quantitative cartilage measures were obtained from 3 T magnetic resonance images at the exam before knee replacement, and longitudinal change during the previous 12 months when available (n=110).
Results Cartilage thickness loss in the central and total medial femorotibial compartment (primary and secondary predictor variables) was significantly greater in case than control knees (AUC=0.59/0.58). Differences in cartilage loss were greater at earlier than later radiographic disease stages (p<0.01 for interaction with KLG). Cartilage thickness loss in the central tibia was the most predictive longitudinal measure (AUC=0.64). Denuded bone areas in the medial femur were the most predictive and discriminatory cross-sectional measure between case and control knees (AUC=0.66).
Conclusions This study demonstrates the predictive value of quantitative, MRI-based measures of cartilage for the clinically relevant endpoint of knee replacement, providing support for their utility in clinical trials to evaluate the effectiveness of structure-modifying intervention.
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Funding The study and image acquisition was funded by the OAI, a public–private partnership composed of five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI study investigators. Private funding partners of the OAI include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline and Pfizer, Inc. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. The image analysis of this study was partly funded by Novartis Pharma AG (Basel, Switzerland), in part by a contract with the University of Pittsburgh (Pivotal OAI MRI Analyses POMA: NIH/NHLBI contract no. HHSN2682010000 21C) and in part by a vendor contract from the OAI coordinating centre at University of California, San Francisco (N01-AR-2-2258). The statistical data analysis was funded by a contract with the University of Pittsburgh (Pivotal OAI MRI Analyses POMA: NIH/NHLBI contract no. HHSN2682010000 21C) and the University of Pittsburgh Multidisciplinary Clinical Research Center (MCRC) for Rheumatic and Musculoskeletal Diseases (P60 AR054731). The sponsors were not directly involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The statistical analysis of the data (based on the entire raw dataset and evaluation of the study protocol, and pre-specified plan for data analysis) was conducted by an independent statistical team at an academic institution (the University of Pittsburgh), which is independent of the commercial sponsor. No compensation or funding from a commercial sponsor was received for conducting the analyses.
Competing interests FE is CEO of Chondrometrics GmbH, a company providing magnetic resonance image analysis services to academic researchers and to industry. He provides consulting services to MerckSerono, Novartis, and Sanofi Aventis, has received speaker honoraria from Merck, GlaxoSmithKline, Genzyme, Medtronic, and Synthes, and has received research support from Pfizer, Eli Lilly, MerckSerono, Glaxo Smith Kline, Centocor R&D, Wyeth, Novartis and Stryker. SC, MIH and WW have part time employment with Chondrometrics GmbH; WW is a co-owner of Chondrometrics GmbH. MIH has provided consulting services to Perceptive. AG is president and co-owner of the Boston Core Imaging Lab (BICL), a company providing MRI reading services to academic researchers and to industry. He provides consulting services to Novartis, Genzyme, Stryker, MerckSerono and AstraZeneca. MRJ is an employee of Novartis Pharma AG. CKK has provided consulting services to Novartis and has received research support from Astra-Zeneca. RMB, ZW, MJH, MCN and DJH have no conflict of interest to declare.
Patient consent Obtained.
Ethics approval The study was approved by the institutional review boards at each of the sites.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The quantitative cartilage data published in this article will be made available after completion of the Pivotal OAI MRI Analyses [POMA] Study: NIH/NHLBI contract no. HHSN2682010000 21C).