Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative

Abstract

Objective: To investigate the predictive and concurrent validity of magnetic resonance imaging (MRI)-based cartilage thickness change between baseline (BL) and year-two (Y2) follow-up (predictive validity) and between Y2 and Y4 follow-up (concurrent validity) for symptomatic and radiographic knee osteoarthritis (OA) progression during Y2→Y4.

Methods: 777 knees from 777 Osteoarthritis Initiative (OAI) participants (age: 61.3 ± 9.0 years, BMI: 30.1 ± 4.8 kg/m2) with Kellgren Lawrence (KL) grade 1-3 at Y2 (visit before progression interval) had cartilage thickness measurements from 3T MRI at BL, Y2 (n = 777), and Y4 (n = 708). Analysis of covariance and logistic regression were used to assess the association of pain progression (≥9 WOMAC units [scale 0-100], n = 205/572 with/without progression) and radiographic progression (≥0.7 mm minimum joint space width (mJSW) loss, n = 166/611 with/without progression) between Y2 and Y4 with preceding (BL→Y2) and concurrent (Y2→Y4) change in central medial femorotibial (cMFTC) compartment cartilage thickness.

Results: Symptomatic progression was associated with concurrent (Y2→Y4: -305 ± 470 μm vs -155 ± 346 μm, Odds ratios (OR) = 1.5 [1.2, 1.7]) but not with preceding cartilage thickness loss in cMFTC (-150 ± 276 μm vs -151 ± 299 μm, OR = 0.9 95% CI: [0.8, 1.1]). Radiographic progression, in contrast, was significantly associated with both concurrent (-542 ± 550 μm vs -98 ± 255 μm, OR = 3.4 [2.6, 4.3]) and preceding cMFTC thickness loss (-229 ± 355 μm vs -130 ± 270 μm, OR = 1.3 [1.1, 1.5]).

Conclusions: These results extend previous reports that did not discern predictive vs concurrent associations of cartilage thickness loss with OA progression. The observed predictive and concurrent validity of cartilage thickness loss for radiographic progression and observed concurrent validity for symptomatic progression provide an important step in qualifying cartilage thickness loss as a biomarker of knee OA progression. CLINICALTRIALS.

Gov identification: NCT00080171.

Keywords: Cartilage thickness; MRI; Osteoarthritis; Progression.

Conflict of interest statement

CONFLICTS OF INTEREST

W. Wirth is a part time employee and co-owner of Chondrometrics GmbH.

D.J. Hunter is a consultant for Flexion and Merck KGaA.

C.K. Kwoh has received research support from Merck Serono and Abbvie.

C. Ladel is an employee of Merck KGaA.

F. Eckstein is CEO/CMO and co-owner of Chondrometrics GmbH, which has received funding from the FNIH OA Biomarker Consortium for the quantitative analysis of cartilage data in this study. He has received consulting fees from Merck KGaA as well as honoraria from Medtronic (less than $10,000 each). M. C. Nevitt and L. Sharma have no conflicts of interest.

Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Figures

Figure 1

Preceding and concurrent change (±95% confidence intervals) in cMFTC cartilage thickness in A) knees with and without symptomatic progression and B) in knees with and without radiographic progression between the year 2 and the year 4 follow-up visit.