The purpose of this study is to investigate the relationship between the clinical and radiographic severity of knee osteoarthritis (OA) and the serum levels of specific biomarkers, namely Fetuin-A and Cartilage Oligomeric Matrix Protein (COMP). Osteoarthritis is a degenerative joint disease characterized by cartilage breakdown and low-grade inflammation. Investigating these biomarkers may help healthcare providers better understand the disease pathology, potentially leading to earlier diagnosis and improved tracking of disease progression. The study will compare two distinct groups: a patient group consisting of 120 individuals diagnosed with Grade 2-4 knee osteoarthritis, and a control group of 60 age- and sex-matched healthy volunteers with no history of joint disorders. Participants will undergo radiographic evaluations using the Kellgren-Lawrence classification system, alongside clinical and functional assessments, including pain severity scales, mobility metrics, and functional questionnaires. Fasting blood samples will be collected from all participants to measure serum Fetuin-A and COMP levels via laboratory analysis, and the Systemic Inflammation Response Index (SIRI) will be calculated. The collected data will be statistically analyzed to determine if biomarker levels significantly correlate with the severity of knee joint degeneration and functional impairment.

Inclusion Criteria:

- Diagnosis of knee osteoarthritis according to ACR (American College of Rheumatology) criteria. Knee osteoarthritis classified as Grade 2, 3, or 4 according to Kellgren-Lawrence (K-L) grading. Volunteering to participate and providing signed informed consent.

Exclusion Criteria:

• Secondary post-traumatic knee osteoarthritis, history of major knee injury or joint infection. Signs of acute joint inflammation (swelling, heat increase, erythema). History of knee surgery (open or arthroscopic). Systemic inflammatory or autoimmune diseases. History of malignancy. Advanced renal or hepatic disease. Diagnosis of Diabetes Mellitus. Current use of systemic corticosteroids. Symptomatic osteoarthritis in other major joints (hip, hand, ankle, spine). Active systemic infection (fever ≥ 38, cough, diarrhea, dysuria, leukocytosis, or elevated CRP).

The study population consisted of two main groups: a patient group and a healthy control group. The patient group included individuals who presented to the Physical Medicine and Rehabilitation Outpatient Clinics of SBÜ Antalya Training and Research Hospital and were diagnosed with primary knee osteoarthritis (Stage 2-4 according to the Kellgren-Lawrence classification system). The control group consisted of healthy volunteers of similar age and gender who did not have a known joint disorder, a history of knee pain, or a systemic inflammatory disease. All participants were selected using a single-center, hospital-based convenience sampling method during the specified study period.