Towards stratification in osteoarthritis: a review of the scientific terminology used in published basic research

Recent attempts to understand the pathophysiology and characteristics of osteoarthritis (OA) have led to the stratification of samples and data. An important part of this process is the use of specific terminology, although the lack of clear definitions for these terms can lead to misinterpretation across different disciplines. In this study, we aimed to assess the frequency of use and chronological appearance of key scientific terminology of four prevalent terms in the field of OA research: PHENOTYPE, SUBTYPE, SUBGROUP and ENDOTYPE. These terms were analysed in conjunction with tissues and fluids associated with OA research, specifically plasma/serum, synovial fluid, synovial membrane, cartilage, meniscus and bone. The method for screening the published literature focused on publications from January 2010 to September 2024, with priority given to studies that reported results from unmanipulated human tissues and applying unbiased analytical methods. Excluded from the analysis were reviews, clinical trials, animal studies, in vitro data, and analyses of pre-existing datasets. The data revealed that the most frequently used term was PHENOTYPE, followed by SUBGROUP and SUBTYPE, with ENDOTYPE being the most recently introduced term in 2019. These terms were rarely defined and often used interchangeably within a single paper, particularly in studies involving cartilage and serum. Notably, the use of these terms has tripled in total over the last 14 years, with an increase in the past decade, reflecting a growing interest in OA stratification, as well as the utility of advanced unbiased analytical methods including microarray and RNA sequencing. The term PHENOTYPE was broadly used and often when describing clinical features, whilst the term ENDOTYPE is used when describing molecular mechanisms related to OA pathogenesis. To improve communication of findings associated with OA stratification, we propose a harmonised application in the use of these stratification terms to prevent misinterpretation and support better communication of OA-related research findings. Building on published terminology, PHENOTYPE could be used to describe clinical features, while ENDOTYPE could be used to describe molecular mechanisms.