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.
Song et al. (Fri,) studied this question.