Effect of Resistance Exercises on Serum IGF-1 Levels in Knee Osteoarthritis

Knee osteoarthritis (OA) is a prevalent degenerative joint disease characterized by pain, functional impairment, and cartilage degradation. Resistance exercises are recommended as a core non-pharmacological treatment for knee OA, yet the exact biochemical mechanisms underlying its clinical benefits remain partially understood. Insulin-like Growth Factor 1 (IGF-1) is a critical anabolic biomarker involved in cartilage matrix synthesis and repair. Furthermore, recent studies suggest that knee OA is a heterogeneous disease, and the "metabolic phenotype" (often associated with obesity, dyslipidemia, insulin resistance, or hypertension) may significantly influence systemic inflammation, disease progression, and the patient's response to physical rehabilitation.

This study is designed to measure the changes in serum IGF-1 levels in patients with knee OA following a structured resistance exercise program, investigate the correlation between changes in serum IGF-1 and clinical improvements as well as radiological severity and evaluate the modifying effect of the metabolic phenotype on the relationship between biomarker changes and clinical outcomes.

This is a prospective, single-center, non-randomized clinical trial. Patients diagnosed with knee OA according to the American College of Rheumatology (ACR) criteria, specifically with a radiological severity of Kellgren-Lawrence grade 2 or 3, will be included in the study. Participants will be non-randomly allocated into two predefined groups at baseline:

1. Metabolic phenotype group: Patients presenting with a metabolic phenotype. (The metabolic phenotype is defined as the presence of metabolic syndrome, using the 2009 Joint Interim Statement criteria. A clinical diagnosis requires the presence of at least three of the following five criteria:

   • Elevated waist circumference (≥ 100 cm in men, ≥ 90 cm in women, based on the 2024 Guidelines of the Society of Endocrinology and Metabolism of Turkey)
   • Elevated blood pressure (Systolic ≥ 130 mmHg and/or Diastolic ≥ 85 mmHg) or receiving treatment for hypertension
   • Elevated fasting blood glucose (≥ 100 mg/dL) or previously diagnosed with diabetes mellitus.
   • Elevated triglycerides (≥ 150 mg/dL) or receiving treatment for hypertriglyceridemia.
   • Reduced HDL cholesterol (\< 40 mg/dL in men, \< 50 mg/dL in women) or receiving treatment for hyperlipidemia.)
2. Non-Metabolic Phenotype group: Patients without a metabolic phenotype.

Both groups will receive the exact same intervention. All participants will undergo a supervised resistance exercise program targeting the lower extremities. The program will consist of for a total duration of 8 weeks.

Fasting venous blood samples will be drawn at baseline and post-intervention (at 8 weeks) to measure serum IGF-1 levels. Clinical status will be assessed using standard questionnaires including The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analog Scale (VAS) for pain. Additionally, quadriceps muscle strength will be evaluated using a hand-held dynamometer at baseline and post-intervention. For radiological evaluation, baseline osteophyte scores will be assessed for all patients using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) system, based on MRI scans obtained within the past year.