Plain radiography or magnetic resonance imaging (MRI): Which is better in assessing outcome in clinical trials of disease-modifying osteoarthritis drugs? Summary of a debate held at the World Congress of Osteoarthritis 2014☆
Section snippets
Arguments commonly provided against radiography, and why they may not hold
There are some frequently pronounced, but relatively superficial arguments about the limitations of radiography, which will be briefly summarized and commented on here, to be extended further in the next few sections of this article:
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Radiography is an historic technique and technologically outdated. Yet, a lot of progress has been made in optimizing radiographic acquisition and analysis methodology, and innovation is still ongoing.
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Radiography provides a small set of structural outcome measures
Semi-quantitative and quantitative outcome measures of x-ray and MRI
Radiographic image assessment encompasses semi-quantitative scores for osteophytes, joint space narrowing (JSN), subchondral bone sclerosis, bone deformity, and Kellgren Lawrence (KLG) grades, for which exist variations in definitions and interpretations. Quantitative radiographic measures include JSW (minimum, mean, area, or fixed location), knee alignment in the frontal plane, subchondral trabecular integrity, and other measures. Semi-quantitative assessment of MRI includes osteophytes,
Technical considerations and reliability
To obtain accurate and reliable (reproducible) measurement of femorotibial radiographic JSW, it is imperative for the x-ray beam to be aligned as parallel as possible with the tibial plateau (Fig. 1A). This can be achieved using fluoroscopically controlled or standardized non-fluoroscopic acquisition protocols. Because minimal JSW (Fig. 1B) is significantly correlated with the inter-margin distance (IMD) [10] between the anterior and posterior tibial rims (Fig. 1A), the IMD should be kept at <1
Relationship with clinical outcomes
Joint structure is commonly viewed as a risk factor and potential surrogate of clinical outcome. Regulatory agencies request structural DMOAD effects to be accompanied by improvement in clinical outcome, and a hope is that treatment effects can be ascertained by imaging well before they translate into clinical benefit. Neogi et al. [24] found that pain was strongly associated with radiographic status, when between-person confounding of pain perception was eliminated in using a between-knee
Sensitivity to change in knee OA and to demonstrating effectiveness of intervention
The sensitivity to change in JSW and cartilage volume/thickness change depends to a great deal on the length of observation and baseline radiographic disease stage [13], [31]; therefore meta-analyses across different studies must be interpreted with caution [32], [33]. Few studies have directly compared the sensitivity to change between both methods: One study reported substantially greater sensitivity to change for a sagittal FISP MRI sequence than for fluoroscopically controlled semi-flexed
Conclusions
Based on current knowledge, radiography and MRI have not been demonstrated to be strongly superior over one another, and for the time being, it therefore appears advisable to use both in parallel in DMOAD trials, to provide more evidence on their relative performance. MRI clearly provides more comprehensive information on articular tissues pathology than radiography, and future research will have to show whether it can identify specific phenotypes of knee OA to be successfully treated by
Role of the funding source
The topic of the debate was chosen by the program committee of the OARSI World Congress 2014, but the content of the debate and of this summary article was selected by the authors without interference of OARSI or any other party.
Potential conflicts of interest
Felix Eckstein is CEO of Chondrometrics GmbH, a company providing MR image analysis services to academic researchers and to industry. He provides consulting services to MerckSerono, Mariel Therapeutics, and Synarc, he has received speaker honoraria from Medtronic, and has received research support from Pfizer, Eli Lilly, MerckSerono, Glaxo Smith Kline, Centocor R&D, Wyeth, Novartis, Abbvie, Stryker, Synarc, Ampio, Kolon, BICL, and Orthotrophix.
Marie-Pierre Hellio Le Graverand is an employee of
Contribution Statement
Both authors made substantial contributions to
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the conception and design of the debate and this summary article,
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drafting the article or revising it critically for important intellectual content,
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and final approval of the version to be submitted.
Acknowledgment
We would like to thank the attendees of the OARSI World Congress in Paris who attended the session and stimulated the subsequent discussion. We would further like to thank our coworkers and collaborators who supported us in preparing the debate and this summary article.
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The debate was supported by OARSI, and both authors received reimbursement of travel cost, accommodation and registration at the World Congress in Paris.