The global prevalence of osteoarthritis (OA) is expected to rise as the population ages, leading to increased physical impairments that often reduce physical activity. Knee OA, in particular, is a leading cause of chronic pain and disability in people over 40. OA progression varies among individuals, with factors such as higher age and body mass index contributing to a more rapid progression. However, research suggests that engaging in physical activity such as hiking and running may help alleviate pain and slow OA progression. However, current literature on the relationship between physical activity and knee OA is largely retrospective, lacks comparative analyses across different physical activity types and rarely considers the intensity of physical activity. To address these gaps, the LoaD study was designed as a prospective cohort study aimed at examining how different physical activity types (ie, hiking, running, cycling and tennis) and their intensities relate to knee OA progression over 24 months in physically active individuals with early signs of the condition.

This prospective cohort study will include 300 participants (75 per physical activity group), who will be followed for 24 months. Eligible participants are aged 45–65, meet the National Institute for Health and Care Excellence (NICE) criteria for clinical knee OA and engage in a minimum weekly activity level for either running (60 min), cycling (120 min), playing tennis (60 min) or hiking (1 hike of 10 km). Baseline and follow-up assessments will include MRI, physical examination (eg, biometrics, lower extremity strength) and blood sampling for molecular biomarker assessment (eg, genetics, inflammatory biomarkers). Participants will receive monthly online questionnaires (eg, demographics, lifestyle, general health, history of knee injuries) and their physical activities will be tracked continuously by global positioning system data from wearable devices. The study’s primary outcomes focus on knee OA progression and symptom changes. These will be assessed through (1) structural progression of knee OA, measured using the MRI Osteoarthritis Knee Score (MOAKS) and (2) clinical symptom progression evaluated by (a) the Knee Injury and Osteoarthritis Outcome Score sport and recreation function subscale and (b) Visual Analogue Scale for pain during an activity nominated by the participant to be the most aggravating for knee pain in the past month (VASNA, 0–10). Differences between groups on the primary outcomes will be analysed using mixed-effects models to determine the impact of activity type and intensity on knee OA progression.

The study is approved by the Erasmus MC Medical Research and Ethics Committee (MREC) (MEC-2022-0420). The results of this study will be made publicly available through peer-reviewed international open-access scientific journals and national and international conferences. Participants will be informed about the results as soon as they are published.