Objective. In this study, the investigators aimed to investigate the efficacy of combined a single platelet-rich plasma (PRP) and physical exercise (leg swing and quadriceps strengthening exercise) versus PRP and hyaluronic acid (HA) combination therapy. Methods. One hundred and six patients with grade Ⅱ-Ⅲ Knee osteoarthritis (KOA) according to the Kellgren-Lawrence classification were randomly divided into intra-articular injection of PRP combined with leg swing and quadriceps strengthening exercise (group A) and intra-articular combination injections of PRP and HA (group B). Patients in group A received twice intra-articular injection of PRP (2 ml, 2 weeks apart) and regular leg swing and quadriceps strengthening exercise for 3 months. Patients in group B received twice intra-articular combination injections of PRP (2 ml) and HA (2 ml) every 2 weeks. The primary outcome measures were Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities (WOMAC) score. The second outcomes included single leg stance test (SLS) and functional activity by 2 minutes walking test (2MWT) and time up and go test (TUGT). All outcomes were evaluated at baseline and after 1,3,6, and 12 months.

Inclusion Criteria:

• patients aged ≥ 45 years old;
• KOA was diagnosed according to the American College of Rheumatology Classification Criteria;
• patients with the Kellgren-Lawrence grade (K-L grade) for KOA of Ⅰ-Ⅲ;
• a history of symptoms more than three month, and patients with independent mobility.

Exclusion Criteria:

• lower limb axial deviation large than 5° (valgus and varus knee);
• patients with diabetes mellitus, sever cardiovascular disease, immunosuppressive status, mental illness or other diseases than might affect the results;
• injections or other invasive treatments into the lower extremities were used in the past three months;
• patients willing to follow the doctor's recommendation for exercise training;
• patients with previous knee fracture or malignancy;
• patients with a previous history of hip or knee joint surgery;
• patients participating in hip or knee muscle strengthening in the past 3 months;
• patients did not complete the intervention strategies or regular follow-up.