Stratification of decompensated osteoarthritis and modern options of the preoperative therapy using Chondroguard® based on pheno- and endotyping

Abstract

Aim: to perform a retrospective analysis of the pattern of changes in the structural and functional characteristics of articular cartilage and biomarkers in the blood serum of patients with knee osteoarthritis (OA), Kellgren-Lawrence Grade 3, and Grade 2 joint dysfunction, taking into consideration the identified phenotypes and endotypes of knee OA during the parenteral treatment with highly purified chondroitin sulfate (CS, Chondroguard®). Patients and Methods: the authors performed a retrospective analysis of the results of the earlier stage of an open prospective controlled randomized study, which included 67 patients with knee OA. The patients were referred to total knee arthroplasty (TKA). All patients received NSAIDs in a standard daily dose. At the stage of open prospective randomized clinical study, the patients were split into the control group (CG, n=35) and the study group (SG, n=32). In addition to NSAIDs, the SG patients received a course of parenteral CS two months prior to TKA. Retrospectively, patients in the SG and CG were divided into subgroups according to three disease phenotypes: an inflammatory phenotype caused by synovitis (CG: n=13; SG: n=11); injury-related phenotype (joint injury in the medical history) (CG: n=10; SG: n=10), and endocrine phenotype (CG: n=12; SG: n=11). Based on the identified phenotypes, the biosamples of the subchondral bone, articular cartilage of the femur and tibia, and the articular capsule obtained during TKA surgery procedure were assessed. Also, the levels of hyaluronic acid, ultrasensitive CRP, TNF-α, IL-6, leptin, adipsin, PIIANP, CTX-1, osteocalcin, MMP-3 and -13, COMP, sclerostin, 25(OH)D3 were determined in the blood at the baseline (visit 0), release from the hospital (visit 1) and 3 months after TKA (visit 3). Results: the morphological analysis of joint tissues and the laboratory blood tests provided a basis for characterizing at the endotype level the following three clinical and pathogenetic knee OA phenotypes: inflammatory, posttraumatic and endocrine. In patients with distinct phenotypes of knee OA, differences were revealed in the intensification of adaptive structural modifications in all layers of the articular cartilage and the extent of inflammation restriction in the synovial membrane of the knee joint, as well as the degradation manifestations in the subchondral bone after a two-month preoperative treatment course with Chondroguard ®. A more pronounced and considerable decrease in the blood levels of all tested compounds along with a significant increase in the blood levels of osteocalcin and 25(OH)D 3 were reported in patients with all phenotypes of knee OA in SG as compared to the changes in the lab tests detected in patients with all phenotypes of knee OA in CG. Conclusion: the extent of CS anti-inflammatory, analgetic, metabolic and structure-modifying effects may depend on endotypes determined in patients with specific OA phenotypes. These findings may pave the way for personalized Chondroguard® therapy to be used in patients with OA of various locations, stages, and degrees of functional impairment by identifying their specific OA phenotypes and endotypes. KEYWORDS: osteoarthritis, phenotype, endotype, biomarkers, hyaline cartilage, synovial membrane, morphology, chondroitin sulfate, Chondroguard, arthroplasty. FOR CITATION: Minasov T.B., Lila A.M., Nazarenko A.G. et al. Stratification of decompensated osteoarthritis and modern options of the preoperative therapy using Chondroguard® based on pheno- and endotyping. Russian Medical Inquiry. 2023;7(3):124–136 (in Russ.). DOI: 10.32364/2587-6821-2023-7-3-124-136.