Does the use of ordered values of subregional change in cartilage thickness improve the detection of disease progression in longitudinal studies of osteoarthritis?

Authors

  • Robert J. Buck,

    Corresponding author
    1. Pfizer Global Research and Development, New London, Connecticut, and StatAnswers Consulting LLC, San Diego, California
    • StatAnswers Consulting LLC, 5392 Renaissance Avenue, San Diego, CA 92122
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  • Bradley T. Wyman,

    1. Pfizer Global Research and Development, New London, Connecticut
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    • Drs. Wyman and Hellio Le Graverand own stock and/or hold stock options in Pfizer, Inc.

  • Marie-pierre hellio Le Graverand,

    1. Pfizer Global Research and Development, New London, Connecticut
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    • Drs. Wyman and Hellio Le Graverand own stock and/or hold stock options in Pfizer, Inc.

  • Martin Hudelmaier,

    1. Institute of Anatomy & Musculoskeletal Research, Paracelsus Medical University, Salzburg, Austria
    2. Chondrometrics GmbH, Ainring, Germany
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  • Wolfgang Wirth,

    1. Chondrometrics GmbH, Ainring, Germany
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  • Felix Eckstein,

    1. Institute of Anatomy & Musculoskeletal Research, Paracelsus Medical University, Salzburg, Austria
    2. Chondrometrics GmbH, Ainring, Germany
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    • Dr. Eckstein has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Novo Nordisk, Inc., BioSyntech, Novartis, and Wyeth, and (more than $10,000) from Pfizer, Inc. and Merck, and owns stock and/or holds stock options in Chondrometrics GmbH.

  • A9001140 Investigators


Abstract

Objective

To propose a novel strategy for more efficiently measuring changes in cartilage thickness in osteoarthritis (OA) using magnetic resonance imaging, and to hypothesize that determining the magnitude of thickness change independent of the anatomic location provides improved discrimination between healthy subjects and OA participants longitudinally.

Methods

A total of 148 women were imaged; 90 were Kellgren/Lawrence (K/L) grade 0, 30 were K/L grade 2, and 28 were K/L grade 3. Magnetic resonance images (3T) were acquired at baseline and at 24 months. Changes in femorotibial cartilage thickness were determined in 5 tibial and 3 femoral medial and lateral subregions, respectively (conventional approach). The new strategy provided ordered values of subregional change in each compartment, ranked according to the direction and magnitude of change.

Results

Using the new ordered values approach, the minimal P value for the differences in 2-year change in medial cartilage thickness of K/L grade 3 and K/L grade 0 participants was 0.001 (Wilcoxon test), with 4 ordered medial subregions differing significantly between both groups. With the conventional approach, only 1 medial subregion differed significantly between K/L grade 3 and K/L grade 0 (P = 0.037). Cartilage thickening was significantly greater in K/L grade 2 versus K/L grade 0 participants in 1 medial subregion using the conventional approach (P = 0.016), and in 2 medial subregions (minimal P = 0.007) using the ordered values approach.

Conclusion

The novel ordered values approach is more sensitive in detecting cartilage thinning in K/L grade 3 and cartilage thickening in K/L grade 2 versus K/L grade 0 participants. The new method may be particularly useful in the context of other comparisons, e.g., a group treated with a disease-modifying OA drug versus one treated with a placebo.

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