Exploratory synovial fluid metabolomics suggests formate as a potential player in post-traumatic osteoarthritis: an 8-year case series report

Abstract Traumatic knee lesions are among the most common injuries in sports and have long been recognized as a major risk factor for the development of post-traumatic osteoarthritis (PTOA). This work aimed at performing a metabolomic analysis of synovial fluid (SF) to identify biomarkers predictive of PTOA progression after acute anterior cruciate ligament or meniscal injury. In this single-center case series report with a mean follow-up of 96 ± 8 months, trauma patients were compared with two control groups [osteoarthritis (OA) and Non-OA]. At the end of follow-up, 44.4% of trauma patients showed signs of radiographic evolution to PTOA, with an interrater reliability of 0.8. Trauma patients exhibited a distinct SF metabolic profile, with PLS-DA models showing good internal cross-validated performance [Q²(cum) ≥ 0.70], supporting consistent metabolic differences between trauma and control groups. Of 30 identified metabolites, 16 showed significant differences between trauma patients and at least one control group after correction for multiple testing. Notably, formate showed the strongest nominal association with subsequent PTOA development, with higher levels in patients who progressed to PTOA (unadjusted p = 0.046); however, this association did not remain significant after correction for multiple testing ( q = 0.995). These findings identify formate as an exploratory candidate biomarker associated with PTOA progression.