Integration of clinical features and metabolomics study reveals sex dimorphism in knee osteoarthritis

Knee osteoarthritis (KOA) is a significant public health concern with increasing prevalence worldwide, exhibiting notable gender disparities in symptom phenotypes. Despite the recognized sexual dimorphism in OA, reliable biomarkers reflecting these gender differences are lacking. This study involved 60 KOA patients from whom we gathered clinical data, urine, and serum samples. Through exploratory metabolomic analysis using untargeted liquid chromatography-tandem high-resolution mass spectrometry (LC-HRMS), we identified candidate sex-specific metabolites. Correlation and least absolute shrinkage and selection operator (LASSO) regression analyses were conducted to identify potential clinical and metabolite markers. Our findings suggest testosterone as a candidate clinical marker showcasing sex differences in KOA. Through the exploration of associations between clinical parameters and metabolic profiles, we pinpointed 3 alpha-diol-3G, a metabolite stemming from the androgen pathway, as a potential marker for sexual dimorphism. This research delivers an investigational sex-specific clinical-metabolic landscape of KOA. Furthermore, our results indicate the potential of androgen-related metabolites, especially testosterone and 3 alpha-diol-3G, which are associated with the gender-specific phenotype of KOA, offering fresh insights and targets worthy of further investigation for the sex-specific pathogenesis of KOA.