ObjectiveThe development of disease-modifying drugs is limited by OA's heterogeneity and the challenge of defining clinical endpoints. Serological biomarkers are considered potential surrogate endpoints, but their contribution from single joints to systemic levels in OA patients is unclear. In this exploratory study we longitudinally assessed systemic biomarker levels' response to tissue damage and healing before and after surgery in patients undergoing knee or hip joint replacement revision for aseptic failure. Patients with chronic pain associated with a prior hip or knee arthroplasty, but not receiving revision surgery were included as control. MethodThe serological biomarker of MMP mediated type III collagen degradation C3M, associated with synovial tissue degradation, was measured at baseline before revision surgery, after revision surgery and at a 6-month follow-up in 48 patients with aseptic loosening of a knee or hip prosthesis and in 18 patients with chronic pain from a hip or knee prosthesis. Longitudinal changes in biomarkers were modeled using linear mixed models. ResultsNo differences between the aseptic loosening and chronic pain groups were observed at baseline. Revision surgery in the aseptic loosening group led to a swift increase in C3M, which normalized within 2–3 months. No changes in biomarker level were observed in chronic pain patients over three months. ConclusionThese findings suggest that tissue damage in a single joint significantly impacts systemic biomarker levels and underscores the relevance of systemic biomarkers in assessing local tissue remodeling.