Identifying the Phenotypic and Temporal Heterogeneity of Knee Osteoarthritis: Data From the Osteoarthritis Initiative

Abstract

Objective: Previous studies discussing phenotypic and temporal heterogeneity of knee osteoarthritis (KOA) separately have fatal limitations that either clustering patients with similar severity or assuming all knees have a single common progression pattern, which are unreliable. This study tried to uncover more reliable information on phenotypic and temporal heterogeneity of KOA.Design: Data were from Osteoarthritis Initiative database. Six hundred and seventy-eight unilateral knees that have greater Kellgren and Lawrence (KL) grade than the contralateral knees at baseline and in all follow-up 48 months were included. Measurements of biomarkers at baseline were chosen. Subtype and Stage Inference model (SuStaIn) was applied as a subtype-progression model to identify subtypes, subtype biomarker progress sequences and stages of KOA.Results: This study identified three subtypes which account for 15, 61, and 24% of knees, respectively. Each subtype has distinct subtype biomarker progress sequence. For knees with KL grade 0/1, 2, 3, and 4, they have different distributions on stage and 26, 53, 89, and 95% of them are strongly assigned to subtypes. When assessing whether a knee has KL (grade ≥ 2), subtypes and stages from subtypes-progression model (SuStaIn) are significantly better fitting than those from subtypes-only (mixture of Gaussians) (likelihood ratio = 105.59, p = 2.2 × 10−16) or stages-only (SuStaIn where setting c = 1) (likelihood ratio = 58.04, p = 2.57 × 10−14) model. Stages in subtypes-progression model has greater β than stages-only model. Subtypes from subtypes-progression model have no statistical significance.Conclusions: For subtypes-progression model, stages contain more complete temporal information and subtypes are closer to real OA subtypes.

Osteoarthritis as an Umbrella Term for Different Subsets of Humans Undergoing Joint Degeneration: The Need to Address the Differences to Develop Effective Conservative Treatments and Prevention Strategies

“…The knee OA patient population is heterogeneous, with different subsets having different characteristics or phenotypes. This heterogeneity can be defined using several different approaches [ 16 , 17 , 18 , 19 ], including the categories discussed in this review. The more successful the research community becomes in delineating subtypes of OA, the more understanding will emerge to rationalize the development of effective interventions.…”

“…This concept that OA is heterogeneous [ 14 , 15 ] and that sub-typing or phenotyping of OA is needed has also been raised by others [ 16 , 17 , 18 , 19 , 20 ] using a variety of criteria. Thus, some are related to metabolic phenotype [ 16 , 18 , 20 ], while others rely on patient characteristics at other levels [ 17 , 19 ]. In addition, biomarkers may be of use to identify subsets of patients with unilateral knee OA who may progress to bilateral knee OA [ 21 ].…”