AB0582 KNEE OSTEOARTHRITIS PHENOTYPES STRATIFICATION
Authors: K. Korochina, T. Chernysheva, I. Korochina, V. Klementeva, G. Kuznetsov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteoarthritis (OA) relevance is determined by its record prevalence with progredient growth throughout the world [1]. Clinical and pathogenic heterogeneity of disease actualizes problem of its stratification [2]. Lack of unified understanding of OA and its phenotype determination results in incredible number of attempts to group OA, using of different classification criteria in last decade. Objectives: To analyze and systematize available OA classifications, proposals and phenotypes, to highlight the most promising of them. Methods: We studied publications from MEDLINE / PubMed and Google Scholar databases found by the keywords “osteoarthritis”, “phenotypes”, “subphenotypes”, “classification”, “subtypes”, “subsets”, “subgroups”, “subpopulations”, “profiles” and “endotypes” in various combinations in English and Russian. We did not set a time frame, but aimed to include as many different methods as possible in order to reflect evolution of scientists’ views on structuring of this disease. Results: A total of 55 OA grouping methods were covered so that OA was structured by different determinants into 6 big boxes. First OA classifications were characterized by complex etiopathogenetic approach, while subsequent studies differed in joint-mediated approach, and the knee joint was undisputed “champion” in this “race”. One of the first attempts to group OA was division into primary, or idiopathic, and secondary, due to known causes. It is now obvious that it is becoming obsolete, and criteria for OA primacy are difficult to determining. Genomic highly specialized studies based on isolation of “favorable” and “unfavorable” genes develops prerequisites to genetic OA classifying. Clinical variants occupy central place as they are the most fully consistent with modern phenotype conception [3], considerating as subtypes of disease shared by underlying pathobiological and pain mechanisms and their structural and functional consequences. Trajectories of OA progression are distinguished by longitudinal design, that is, the determinants for grouping here are disease characteristics in dynamics. The ancestor of structural OA trajectories can be considered Kellgren-Lawrence grades; subsequent studies identified complex of clinical, laboratory and morphological factors contributing to development of trajectories. Structural OA variants are diverse depending on visualization methods, and many of them can be naturally considered phenotypes, since they drive certain clinical OA manifestations. Morphological changes were described at macro- and microscopic levels; it is interesting to note the absence of histopathological norm in patients without OA. Laboratory profiles of patients are determined by content of systemic (serum, urinary) or local, “proximal” (in synovial fluid) biomarkers, which seem to be more precise. Metabolomic analysis is perspective new direction of laboratory studies based on joint metabolic products identification in the synovial fluid. New trend in OA research is molecular phenotyping. The specific molecular pathway explaining observed phenotype properties is called “endotype”. Endotype is related to certain pathobiological scenario, and laboratory markers are potentially effective for its diagnosis. Conclusion: Thus, a large amount of accumulated information and its diversity soon will probably lead to qualitatively new knowledge level with deep understanding of phenotype-associated strategy for managing OA patients. References: [1]Wallace IJ, Worthington S, Felson DT, et al. Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci USA. 2017 Aug 29;114(35): 9332-9336. doi: 10.1073/pnas.1703856114 Epub 2017 Aug 14. [2]Deveza LA, Nelson AE, Loeser RF. Phenotypes of osteoarthritis: current state and future implications. Clin Exp Rheumatol 37 Suppl 2019;120(5):64-72. [3]Van Spil WE, Bierma-Zeinstra SMA, Deveza LA, et al. A consensus-based framework for conducting and reporting osteoarthritis phenotype research. Arthritis Res Ther. 2020;22(1):54. doi:10.1186/s13075-020-2143-0 Disclosure of Interests: None declared.