Current status of catabolic, anabolic and inflammatory biomarkers associated with structural and symptomatic changes in the chronic phase of post-traumatic knee osteoarthritis– a systematic review

Post-traumatic OA (PTOA) can occur within 5 years after a significant injury and is a valuable paradigm for identifying biomarkers. This systematic review aims to summarise published literature in human studies on the associations of known serum and synovial fluid biomarkers at least a year from injury to structural, symptomatic changes and underlying PTOA processes. A systematic review was performed using PRISMA guidelines, prospectively registered on PROSPERO (CRD42022371838), for all ‘wet’ biomarkers a year or more post-injury in 18–45-year-old participants. Three independent reviewers screened search results, extracted data, and performed risk of bias assessments (Newcastle-Ottawa Scale). Study heterogeneity meant a narrative synthesis was undertaken, utilising SWiM guidelines. 952 studies were identified, 664 remaining after deduplication. Following first-round screening, 53 studies underwent second-round screening against pre-determined criteria. Eight studies, with 879 participants (49 ​% male), were included, measuring serum (n ​= ​7), synovial fluid (SF, n ​= ​6), or both (n ​= ​5). The pooled participant mean age was 29.1 (±4). 51 biomarkers were studied (serum ​= ​38, SF ​= ​13), with no correlation between paired serum and SF samples. One serum biomarker, cartilage oligomeric matrix protein (COMP), and four SF biomarkers, interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF), and COMP, were measured in multiple studies. Associations were described between 11 biomarkers related to catabolism (n ​= ​4), anabolism (n ​= ​2), inflammation (n ​= ​4) and non-coding RNA (n ​= ​1), with OA imaging changes (X-ray and MRI), pain, quality of life and function. Widespread differences in study design and methodology prevented meta-analysis, and evidence was generally weak. A unified approach is required before widespread research and clinical biomarker use.