AUTHOR=Li Mengjiao , Lan Lan , Luo Jiawei , Peng Li , Li Xiaolong , Zhou Xiaobo 

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

JOURNAL=Frontiers in Public Health

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2021.726140

DOI=10.3389/fpubh.2021.726140

ISSN=2296-2565

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Design:</bold> 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.</p><p><bold>Results:</bold> 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, <italic>p</italic> = 2.2 × 10<sup>−16</sup>) or stages-only (SuStaIn where setting <italic>c</italic> = 1) (likelihood ratio = 58.04, <italic>p</italic> = 2.57 × 10<sup>−14</sup>) model. Stages in subtypes-progression model has greater β than stages-only model. Subtypes from subtypes-progression model have no statistical significance.</p><p><bold>Conclusions:</bold> For subtypes-progression model, stages contain more complete temporal information and subtypes are closer to real OA subtypes.</p>