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

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Abstract

Osteoarthritis (OA) is the most common disease of synovial joints and currently lacks treatment options that modify structural pathology. Imaging is ideally suited for directly evaluating efficacy of disease-modifying OA drugs (DMOADs) in clinical trials, with plain radiography and MRI being most often applied. The current article is based on a debate held on April 26, 2014, at the World Congress of Osteoarthritis: The authors were invited to contrast strengths and limitations of both methods, highlighting scientific evidence on reliability, construct-validity, and correlations with clinical outcome, and comparing their sensitivity to change in knee OA and sensitivity to DMOAD treatment. The authors concluded that MRI provides more comprehensive information on articular tissues pathology, and that implementation of radiography in clinical trials remains a challenge. However, neither technique has thus far been demonstrated to be strongly superior over the other; for the time being it therefore appears advisable to use both in parallel in clinical trials, to provide more evidence on their relative performance. Radiographic JSW strongly depends on adequate positioning; it is not specific to cartilage loss but also to the meniscus. MRI provides somewhat superior sensitivity to change compared with the commonly used non-fluoroscopic radiographic acquisition protocols, and has recently provided non-location-dependent measures of cartilage thickness loss and gain, which are potentially more sensitive in detecting DMOAD effects than radiographic JSW or region-specific MRI. Non-location-dependent measures of cartilage thickness change should thus be explored further in context of anabolic and anti-catabolic DMOADs.

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:

  • Radiography is an historic technique and technologically outdated.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.

  • 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

  • (1)

    the conception and design of the debate and this summary article,

  • (2)

    drafting the article or revising it critically for important intellectual content,

  • (3)

    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.

References (46)

  • E. Schneider et al.

    Equivalence and precision of knee cartilage morphometry between different segmentation teams, cartilage regions, and MR acquisitions

    Osteoarthritis Cartilage

    (2012)
  • W. Wirth et al.

    Sensitivity to change of cartilage morphometry using coronal FLASH, sagittal DESS, and coronal MPR DESS protocols—comparative data from the Osteoarthritis Initiative (OAI)

    Osteoarthritis Cartilage

    (2010)
  • F. Eckstein et al.

    Trajectory of cartilage loss within four years of knee replacement—a Nested Case–Control Study from the Osteoarthritis Initiative

    Osteoarthritis Cartilage

    (2014)
  • F. Cicuttini et al.

    Comparison of conventional standing knee radiographs and magnetic resonance imaging in assessing progression of tibiofemoral joint osteoarthritis

    Osteoarthritis Cartilage

    (2005)
  • F. Eckstein et al.

    How do short-term rates of femorotibial cartilage change compare to long-term changes? Four year follow-up data from the Osteoarthritis Initiative

    Osteoarthritis Cartilage

    (2012)
  • D.J. Hunter et al.

    Responsiveness and reliability of MRI in knee osteoarthritis: a meta-analysis of published evidence

    Osteoarthritis Cartilage

    (2011)
  • W.M. Reichmann et al.

    Responsiveness to change and reliability of measurement of radiographic joint space width in osteoarthritis of the knee: a systematic review

    Osteoarthritis Cartilage

    (2011)
  • W. Wirth et al.

    Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis: responsiveness data from the Osteoarthritis Initiative

    Osteoarthritis Cartilage

    (2013)
  • W. Wirth et al.

    MRI-based extended ordered values more efficiently differentiate cartilage loss in knees with and without joint space narrowing than region-specific approaches using MRI or radiography—data from the OA initiative

    Osteoarthritis Cartilage

    (2011)
  • A. Guermazi et al.

    Motion for debate: osteoarthritis clinical trials have not identified efficacious therapies because traditional imaging outcome measures are inadequate

    Arthritis Rheum

    (2013)
  • S. Trattnig et al.

    imaging of cartilage and its repair in the knee—a review

    Eur Radiol

    (2009)
  • P.M. Jungmann et al.

    Cartilage repair surgery: outcome evaluation by using noninvasive cartilage biomarkers based on quantitative MRI techniques?

    Biomed Res Int

    (2014)
  • J.P. Pelletier et al.

    What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis?

    Ann Rheum Dis

    (2013)
  • Cited by (0)

    The debate was supported by OARSI, and both authors received reimbursement of travel cost, accommodation and registration at the World Congress in Paris.

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