Quantitative MRI measures of cartilage predict knee replacement: a case–control study from the Osteoarthritis Initiative

Abstract

Abstract:Objective: Knee osteoarthritis is a highly prevalent disease, commonly requiring joint replacement; it substantially reduces quality of life and increases health care utilization and costs. We 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 multicenter observational cohort of 4796 participants with or at risk of knee osteoarthritis. 127 knees were replaced between baseline and four years follow-up, and one control knee per case matched for baseline radiographic disease stage (KellgrenLawrence grade, KLG), gender, and age. Quantitative cartilage measures were obtained from 3 Tesla magnetic resonance images at the exam before knee replacement, and longitudinal change during the prior 12 months when available (n=110).Results: Cartilage thickness loss in the central and total medial femoro-tibial compartment (primary and secondary outcomes) was significantly greater in case than in control knees (AUC=0.59/ 0.58). Differences in cartilage loss were greater at earlier than at 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). Cross-sectionally, denuded bone areas in the medial femur distinguished case and control knees most strongly (AUC=0.66). Conclusions:This study demonstrates the predictive value of quantitative, magnetic resonance imaging-based measures of cartilage for the clinically relevant endpoint of 4 knee replacement, providing support for their utility in clinical trials to evaluate the effectiveness of structure modifying intervention.

Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial

“…Quantitative MRI measures of cartilage thickness loss were shown to contribute to prediction of knee replacement in a 4-year natural history study of OA (26). However, we lack an estimate of the extent of structural modification required to provide patient benefit in the clinical trial setting.…”

“…The primary end point (central subregions of the medial femorotibial compartment) was selected because previous results indicated that the central medial femorotibial compartment shows the greatest rate of change and sensitivity to change in cartilage thickness (20,24,26,42). In light of the previous trials showing more marked treatment effects on the lateral knee compartment as compared to the medial knee compartment (40,41), it is interesting to note that the primary end point of the present trial was not met, while dose-dependent treatment effects were found for the lateral knee compartment (lateral femorotibial compartment).…”

“…The primary efficacy end point was the longitudinal change from baseline in central medial femorotibial compartment cartilage thickness at 6 months and 12 months, as assessed using quantitative MRI (qMRI). This end point was chosen since it has been shown to be the most sensitive to change (highest ratio of the mean change divided by the SD of change across participants) (24)(25)(26) The primary safety end points were local and systemic treatment-emergent adverse events (AEs), acute inflammatory reactions, laboratory findings (blood chemistry, hematology, urinalysis), vital signs, and electrocardiographic results (Supplementary Table 1). Treatment-emergent AEs were defined as any AEs with start dates on or after the date of the first injection of study medication and up to 30 days after the last injection, or AEs classified as possibly or probably related to study medication, with start dates on or after the date of the first injection of study medication and up to 30 days after the trial termination visit.…”

Can Structural Joint Damage Measured with MR Imaging Be Used to Predict Knee Replacement in the Following Year?

“…In comparison, arthroscopy demonstrates only the articular surface and does not allow evaluation of other important tissues, such as the subchondral bone, and it is not feasible to invasively assess knee joints in an observational study over several time points. By using a similar casecontrol design but a quantitative MR imaging approach that allows assessment of different cartilage metrics, we have recently shown that cartilage thickness in the central medial tibiofemoral compartment is diminished in knees undergoing knee replacement compared with those that do not (15).…”

“…Since joint preservation represents the ultimate clinical goal of any therapeutic attempt, imaging biomarkers that allow prediction of joint replacement may serve as prognostic markers, may aid in the decisionmaking process for surgery, and may eventually replace radiographic joint space assessment in disease modification trials as an intervention effectiveness marker (14,15).…”