Effect of aerobic exercise of different intensity on articular cartilage metabolism in patients with knee osteoarthritis: A randomized controlled trial

BACKGROUND: Osteoarthritis (OA) of the knee is a leading cause of disability worldwide, yet optimal exercise intensity for cartilage protection remains unclear. This randomized controlled trial investigated dose-response effects of aerobic exercise intensity on cartilage metabolism, clinical symptoms, and structural outcomes in knee OA patients. METHODS: One hundred twenty participants with knee OA (Kellgren-Lawrence grade 2-3) were randomly assigned to low-intensity (50-60% heart rate reserve [HRR]), moderate-intensity (60-70% HRR), high-intensity (70-80% HRR) treadmill walking or stationary cycling, or a control group for 12 weeks (3 sessions/week). Heart rate was continuously monitored using Polar H10 chest-strap monitors. Primary outcomes were serum C-terminal telopeptide of type II collagen and cartilage oligomeric matrix protein levels. Secondary outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain, 6-minute walk test, and magnetic resonance imaging-assessed cartilage morphology. Data were analyzed using mixed-model repeated measures analysis of variance with IBM SPSS Statistics version 26.0 (IBM Corp.). RESULTS: The high-intensity group demonstrated the greatest reductions in C-terminal telopeptide of type II collagen (-28.5%, P < .001) and cartilage oligomeric matrix protein (-22.3%, P < .001), the largest improvements in WOMAC scores (-45.3%, P < .001) and VAS pain (-52.5%, P < .001), and the greatest increases in cartilage thickness (+4.2%) and volume (+3.8%). A significant dose-response relationship was confirmed (group × time interaction: F (3108) = 4.82, P = .003). Among participants in the high-intensity group, 73% achieved the minimal clinically important differences (MCID) for WOMAC total score and 80% achieved the MCID for VAS pain. The 6-minute walk test improvement in the high-intensity group (71 m) exceeded the established MCID of 26 m. No serious adverse events were reported; minor events (transient knee pain exacerbation and delayed-onset muscle soreness) resolved spontaneously within 48 to 72 hours. CONCLUSIONS: Appropriately prescribed high-intensity aerobic exercise safely and effectively improved cartilage metabolism, alleviated symptoms, and enhanced functional capacity in knee OA patients. These findings support revising current conservative exercise recommendations upward when tolerable.