Our overall hypothesis is that a sudden ambulatory load reduction (caused by corrective osteotomy) leads to changes in cartilage biology that delay or reverse osteoarthritic processes determining the clinical outcome and representing an in vivo model for assessing cartilage mechanosensitivity.

Although osteoarthritis (OA) is the most common degenerative joint disease and despite international research efforts, to date the factors involved in the initiation and progression of this debilitating disease are poorly understood, diagnostic markers are lacking and there is no cure. High tibial osteotomy (HTO) is a well-accepted therapy for patients with knee OA and varus alignment aimed at re-establishing a more even distribution of ambulatory load between the affected medial knee compartment and the lateral knee compartment. However, the survival rate of HTO is only around 75% after 5 years. There is some evidence that the change in ambulatory load after HTO may be more relevant than the post-operative static alignment although this relationship has not yet been investigated. Because of the large changes in ambulatory load with HTO, the investigators propose that corrective osteotomy may serve as a valuable model for studying the effect of changes in ambulatory load on in vivo cartilage mechanobiology in patients with knee osteoarthritis. Our previous work has shown that serum biomarkers for cartilage increase after a 30-minute walking exercise (termed 'walking stress test') and indicated that these changes may be associated with the accumulated ambulatory load during the test.

Patients with medial compartment knee OA and varus alignment will be clinically assessed (including mechanical axis measurement from radiographs) and complete questionnaires on physical function prior to corrective osteotomy. Patients will complete a walking stress test with blood sampling to assess load-induced changes in serum biomarker concentrations, and undergo gait analysis to assess the external knee adduction moment. Once full load bearing is achieved, the mechanical axis will be measured from radiographs. Patients will complete the questionnaires and a second walking stress test with blood sampling and undergo gait analysis 6 months after corrective osteotomy. At the 12-month follow-up, subjects will complete the questionnaires.

Inclusion Criteria:

• radiographically diagnosed and isolated symptomatic medial compartment knee OA undergoing corrective osteotomy (Kellgren-Lawrence grade 2 or 3)
• pain level not limiting physical activity participation
• sports participation (at least once/week).

Exclusion Criteria:

• Use of walking aids
• inability to walk for 30 minutes
• age < 18 years (before maturation) or age >70 years
• due to advanced general sarcopenia (degenerative loss of muscle mass in aging)
• body mass index (BMI) > 35 kg/m2
• active rheumatic disorder
• prior neuromuscular impairment (e.g. stroke)
• conditions other than knee OA that could cause abnormal patterns of locomotion
• prior hip, knee, and ankle prosthesis or osteotomy of the lower extremities
• prior spine surgery; other major medical problems
• investigators and their immediate families are not permitted to be subjects
• persons who have previously completed or withdrawn from this study
• patients currently enrolled in another experimental (interventional) protocol

patients with knee osteoarthritis scheduled for corrective osteotomy