Background: Knee osteoarthritis (KOA) is characterized by chronic degeneration or wear of the articular cartilage, cartilage degeneration, fragmentation, and hardening, as well as bone spur formation and synovial inflammation. Over time, these changes occur slowly, and bone wear becomes more severe. This in turn causes pain, stiffness and swelling. It has an impact on normal work and life. To understand the mechanism and monitoring index of cartilage injury in the elderly population and prevent osteoarthritis. The purpose of this study was to compare the changes of serum cytokine biomarker levels in elderly patients with knee injury and osteoarthritis, and explore the correlation with the severity of lesions, which is conducive to early diagnosis and prevention of knee diseases. Objective: To investigate the differences in serum concentrations of matrix metalloproteinase-3 (MMP-3) and cartilage oligomeric matrix protein (COMP) in elderly patients with osteoarthritis, knee fracture or ligament injury. Methods: A total of 36 elderly KOA patients who underwent knee replacement in our hospital from July 2021 to May 2023 were selected as the observation group, and 36 elderly patients with knee fractures, patellar fractures, ligament or meniscus injuries who were treated during the same period were selected as the control group for the study. The age, gender, weight and other data of the patients were compared. The anteroposterior and lateral radiographs of the knee joints were examined for the first time, and the Kellgren and Lawrence (KL) score was used to compare the severity of KOA. The levels of serum MMP-3 and COMP in the two groups of patients were tested by enzyme-linked immunosorbent assay, and the changes and sensitivity of the two biomarkers in elderly knee diseases were compared and analyzed. Results: (1) Among the 72 knee joints included in the study, 36 cases were assigned to each group. No significant differences were observed in gender, age, or weight between the two groups (P > 0.05). (2) The concentrations of serum MMP-3 and COMP in the observation group were significantly higher than those in the control group. Conclusion:The elevated levels of COMP and MMP-3 in patients with knee osteoarthritis (KOA) suggest a potential correlation with disease progression, as their concentrations increased with worsening severity. These biomarkers may hold significant value for early detection, diagnosis, and prevention of KOA in elderly populations, warranting further investigation.