RATES OF QUANTITATIVELY-DEFINED CARTILAGE LOSS DIFFER BETWEEN DIFFERENT STRUCTURAL KNEE OSTEOARTHRITIS PHENOTYPES - DATA FROM THE FNIH BIOMARKER CONSORTIUM STUDY.

Authors

F W Roemer, A Guermazi, J E Collins, D J Hunter, W Wirth

Published in

Osteoarthritis imaging. Volume 6 Suppl 1. Pages 100444.

Abstract

MRI-based structural stratification may help enrich clinical trial cohorts, considering the expected mode of action of a potential DMOAD candidate. The Rapid OsteoArthritis MRI Eligibility Score (ROAMES) system enables structural phenotyping and may therefore be advantageous to include in clinical trial screening efforts ¹. Currently, it is unknown whether different structural phenotypes, as defined by ROAMES, exhibit different rates of quantitatively defined cartilage loss over 24 months.
To assess whether knees with a distinct structural phenotype - using two different definitions - exhibit greater rates of femorotibial cartilage thickness loss compared to those with other phenotypes, and to those not exhibiting any particular phenotype. A secondary aim was to evaluate whether the number of concomitant phenotypes increases the risk of cartilage loss.
The FNIH study was designed as a case-control study within the OAI cohort, with a predetermined number of index knees selected based on clinical and structural outcomes. MRI was performed on 3T systems. MRIs were read according to the MOAKS system. Knees were stratified into either no phenotype, cartilage-meniscus, inflammatory and subchondral bone phenotypes. In addition, we differentiated whether a knee had 0, 1, 2, or 3 phenotypes. We used two definitions for phenotypic stratification, the original ROAMES definition and a published secondary, less stringent definition ². Quantitative cartilage thickness analysis was based on manual segmentation of the femorotibial cartilage, with blinding to time point. The current study focused on the mean cartilage thickness in the total femorotibial joint. Quantitative cartilage thickness change was computed as an absolute difference between 24 months and baseline value (mm). Between-group comparisons were performed using analysis of covariance (ANCOVA), adjusting for demographic and clinical variables for the different phenotype subgroups (using both definitions) vs. those without any phenotype and vs. those with another phenotype, separately. In addition, subgroups defined by the number of phenotypes present were compared.
484 Kellgren-Lawrence 2 and 3 knees were included. The mean age of the participants was 62 years, 60% were women; the average BMI was 30 kg/m². According to the primary definition, 362 (75%) did not fulfil criteria for any phenotype, while 94 (19%) exhibited the bone phenotype, 22 (5%) the cartilage/meniscus phenotype and 19 (4%) the inflammatory phenotype. When applying the less stringent secondary definitions, these numbers were 274 (57%), 94 (19%), 104 (21%), and 102 (21%), respectively. Using the original ROAMES definition, knees with a bone phenotype showed greater rates of cartilage loss compared to those without a phenotype (mean adj. difference (MAD): -0.09 mm,95%CI [-0.14, -0.03]) and to those with other phenotypes (MAD: -0.15 mm,95%CI [-0.27, -0.03]). Regarding the secondary definition, all phenotypes showed greater rates of cartilage loss than those with no phenotype present (Table 1). Using the secondary definition, an increasing number of phenotypes present showed greater rates of cartilage loss. In a sensitivity analysis focusing on medial compartment cartilage loss, very similar results were observed.
Knees with a bone structural phenotype (using the original ROAMES definition) or any phenotype present (using the secondary definition) show greater rates of cartilage loss in the total femorotibial joint compared to those without a phenotype present. Using the secondary, less stringent definition, two or more phenotypes concomitantly present increased rates of cartilage loss compared to those without a phenotype. Phenotypic stratification appears to provide insights into expected rates of cartilage loss and may be useful to consider when selecting patients for inclusion in clinical trials.

PMID:
42622178
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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