This study aims to study use of viscosupplementation as a treatment of pain for young individuals who are active. Typically viscosupplementation is considered an intervention for knee osteoarthritis often for older patients who are less active. Many young active patients can also develop knee osteoarthritis after trauma or surgery or for congenital reasons. Treatment of these patients commonly are steroid injections which have more biologically detrimental effects for cartilage compared to viscosupplementation Synvisc One injections which are a single injection will be used to determine effectiveness of reducing pain and maintaining an active healthy lifestyle for younger patients aged 30-50 years old.

This study will be an open label longitudinal cohort study with natural history over 3 years. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study. Subjects enrolled in the cohort will have baseline functional testing performed including a motion gait analysis, 12 minute walk test, and 3-day accelerometer data. Subjects will receive a single 6 mL intra-articular injection of hylan G-F 20 in the target knee at baseline. All ongoing treatments will be monitored at 6 month intervals over the 3 year duration of the study. Patients can receive any other conservative treatments (e.g., oral medications, physical or other therapy, acupuncture, etc., except other injection treatments) and current treatments will be documented during each patient encounter. An initial injection of hylan G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20 gauge needle. A face to face follow up visit will be carried out 6 months after first injection with additional face to face meetings every 6 months thereafter unless the subject requires an additional injection of hylan G-F 20. Hylan G-F 20 treatments can be administered up to three times each year during the study duration. After each injection, follow up measures will be carried out using secure e-mail or phone contact at 6 weeks, 12 weeks, 18 weeks after each in-office evaluation or injection. Follow up will consist of WOMAC, Lysholm score, and Tegner score. Patients may return for retreatment of hylan G-F 20 if symptoms recur after at least 4 months following their previous injection and they meet the inclusion criteria with pain levels of WOMAC A1, C8, C9, C10 and/or C23 equaling 2 or more. Patients requiring three injections of hylan G-F 20 in 4 months or less will be allowed to exit the cohort after their six-month follow up following the third injection. Otherwise, patients will be followed until they reach the 3 year follow up, or drop out for other injection treatments or surgical treatment. Therefore, patients would potentially be able to receive up to 9 injections during the 3 year study.

Inclusion Criteria:

• Male or female patients aged 30-50 years
• History of symptomatic unilateral primary or secondary knee OA for more than 6 months
• Signed written informed consent
• Radiographic evidence of Kellgren-Lawrence Grade I or II OA of the target knee
• Body Mass Index (BMI) < 30 kg/m2
• Activity criteria (Tegner score > 3)
• Continued target knee OA pain despite conservative treatment ≥ 3 months (e.g., weight reduction, physical therapy, analgesics)
• Willing to withhold intake of NSAIDs (including COX-2 inhibitors) and analgesics, for a washout period of minimum 3 days up to 21 days prior to baseline visit (depending on medication)
• Willing to discontinue prohibited treatments and medications throughout study period

Baseline inclusion criteria

• Completed OA medication washout period
• Target knee pain 4-8 (0-10 NRS) during most painful knee movement (Worst Knee Pain)
• If female, must have had a negative urine pregnancy test and used a medically acceptable form of contraception for at least 1 month prior to baseline and agree to continued use of contraception for the duration of the study. Otherwise, females must be surgically sterile, or postmenopausal (as documented in medical history) for at least 1 year. The fetal safety profile for G-F 20 is unknown. Pregnancy will affect the individual's regular activity levels. Females who become pregnant during the study will be excluded from the study. Subjects who become pregnant will be followed up by telephone every 3 months to check for any adverse effects. They will also be recommended to follow routine obstetric visits. Males should be able to father children as it has no expected effects on activity levels.

Exclusion Criteria:

• Known allergy to hylan G-F 20 or any of its components, or to avian proteins, eggs, feathers, down, or poultry
• Clinically apparent tense effusion or other acute inflammation of the target knee at baseline
• History of target knee viscosupplementation treatment
• History of major surgery for OA in target knee including arthroplasty or tibial osteotomy
• Arthroscopic surgery or intraarticular steroid injection in target knee within six months of baseline visit
• Significant (as judged by the Investigator) alignment deformity of target knee
• Ipsilateral symptomatic OA of hip or ankle; contralateral symptomatic OA of hip, knee, or ankle

History of:

• Septic OA of any joint
• Inflammatory arthropathy such as RA, gout, pseudogout, lupus, crystalline inflammatory arthropathy
• Active infection of lower extremity
• Known significant acute and/or concurrent medical disease including, but not limited to current malignancy, history of transplant surgery, congestive heart failure, significant unstable cardiovascular disease, renal hepatic pulmonary, endocrine, metabolic, or GI condition
• Any known contraindication to acetaminophen
• Venous or lymphatic stasis in either leg
• Peripheral vascular disease
• Patient has been prescribed chronic opioid analgesics at time of baseline visit
• Concurrent multi-system or multi-limb trauma
• Patient plans to become pregnant during study period
• Patient plans to move significantly out of area, have surgery, or initiate or cease other OA treatments
• Knee pain improves during washout period
• Workman's Comp patient

Adverse event data was collected at 6, 12, and 18 weeks after each injection/clinic visit, up to 3 years for each participant.