Osteoarthritis (OA) of the knee can be characterized by focal and progressive loss of articular cartilage. Radiographic evidence of OA occurs in most people by age 65 and in about 80% of those aged over 75 years old [1]. Joint space narrowing, osteophytes, and bony sclerosis can be seen in patients diagnosed with painful knee osteoarthritis. The International Cartilage Repair Society rating scale classifies OA as the following: Grade I – Nearly Normal (soft indentation and/or superficial fissures and cracks), Grade II- Abnormal (lesions extending down to <50% of cartilage depth), Grade III- Severely Abnormal (Cartilage defects extending down >50% of cartilage depth as well down to calcified layer and down to but not through the subchondral bone, blisters included), Grade IV- Exposed subchondral bone [2]. Treatment of Grade II-IV OA can include exercising, bracing, NSAID’s, narcotic pain relievers, topical pain solutions, physical therapy, and viscosupplementation. Total knee arthroplasty is a surgical option for patients with severe grade IV OA [3].

Viscosupplementation injections are made from Hyaluronic acid, a polysaccharide chain made of repeating disaccharide units of N-acetylglucosamine and glucuronic acid extracted from rooster combs [4]. The healthy human knee contains about 2mL of synovial fluid, with a hyaluronic acid concentration of 2.5 to 4.0 mg/ml. In knees with OA the HA concentration decreases to about 1-2mg/ml [4]. HA injections are beneficial for the treatment of knee OA due to its viscoelastic properties as well as its anti-inflammatory, anabolic, and analgesic properties. HA’s viscoelastic properties help the knee in shock absorption and is an effective knee lubricant [5]. HA with a high molecular weight has also been shown to elicit anti-inflammatory effects by inhibiting arachadonic acid release in inflamed joints [6]. Intra-articular HA modulates pain perception directly through inhibition of nocioreceptors or indirectly binding to substance P 4. HA injections have been shown to have a therapeutic effect at 4 weeks post-injection, with a peak at 8 weeks and extension to over 6 months [7-9].

HA products can differ in method of production, molecular weight, and dosing instructions.Synvisc (Hylan G-F 20) is an elastoviscous high molecular weight fluid containing cross-linked HylanA&Hylan B polymers. Hylan A (80%) is a soluble high MW molecule (6.000.000 DA), while Hylan B (20%) is an insoluble gel. The cross-linking of the two allows a longer residence time into the joint than that of linear HA products [10]. HA products that are cross-linked have been shown to be more effective and have less adverse effects than non cross-linked HA injections [11,5]. HA is cleared rapidly from the joint after injection (20 hrs), but in patients pain and function improvement can persist for months after treatment [12].

HA injection effectiveness can be measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The KOOS is a self-reported score that covers five dimensions that are determined separately: pain, symptoms, activities of daily living, sport and recreation function, and knee related quality of life. The KOOS is organized to ensure content validity for older patients with osteoarthritis as well for younger or more physically active patients. Questions from the Western Ontario and MacMaster Universities (WOMAC) Osteoarthritis index (an outcome measure covering pain, stiffness, and function) are included in their original form in the KOOS questionnaire [13]. KOOS scores range from 0-100, with zero representing extreme knee problems and 100 representing no knee problems.

The objective of this study was to retrospectively analyze KOOS scores and perform an analysis of the efficacy of intra-articular injections of Synvisc® for the treatment of Grade II-IV lateral tibio-femoral, medial tibio-femoral, and patellofemoral knee OA in patients.

Methods

A convenience sample of 90 patients (107 injections) over a period of 6 years with unilateral of bilateral painful Grade II-IV knee OA were given a single or bilateral intra-articular injection of 6mL of Hylan G-F 20 by the senior author [14-17] patients received bilateral injections which accounts for the difference between the number of patients and the number of injections.The average age of subjects in our cohort was 60 years of age with a range of 41-83 years old and a standard deviation of 6 years. Patients were included if they completed a baseline KOOS survey and a 6 week follow up KOOS survey after intra-articular injection of Hylan G-F 20. Patients were excluded if there were no completed KOOS post-survey, knee MRI, or surgery reports to determine OA grade.

Grades and compartment of patient OA was determined by patient MRI reports and arthroscopic surgery reports. OA was identified as either mild (Grade II), moderate (Grade III), and severe (grade IV).OA grade was then classified by compartment; Patellofemoral (PF), MedialTibio-femoral weight bearing (M), and lateralTibio-femoral weight bearing (L). Patients had different OA grades for different compartments which was analyzed and compared.For comparisons of the quantitative measures between the pre and post KOOS survey scores, a paired t-test was used.

Results

In patients with grade II patellofemoral OA, KOOS symptom, pain, and ADL scores improved significantly from baseline to the 6 week follow-up (p<.05). No significant changes were seen with the other two scores for grade II PF OA. In patients with grade III PF OA underwent significant improvement in the KOOS scores of symptoms and pain (p<.05). No significant changes were seen in the other KOOS scores. In patients with grade IV PF OA a significant improvement in pain was seen among KOOS scores. No significant changes were seen in the other KOOS scores (Table 1).

In patients with grade II medial compartment knee OA no significant changes in KOOS scores were seen. In patients with grade III medial OA a significant improvement in pain was seen in KOOS score (p<.05). No significant changes were seen in the other KOOS scores. In patients with grade IV medial OA, a significant increase in the pain and knee-related quality of life KOOS scores were seen (p<.05). No significant changes were seen in the other categories (Table 2).

In patients with grade II lateral compartment knee OA significant changes in sports and recreation function were seen in KOOS score (p<.05). No significant changes were seen in the other KOOS scores. In patients with grade III lateral compartment OA significant improvement in the KOOS categories symptoms, pain, and activities of daily living were seen (p<.05). No significant changes were seen in the other categories. In patients with grade IV lateral OA, significant improvements in symptoms, pain, and ADL were seen in KOOS scores (p<.05). Other scores showed no significant changes (Table3).

Discussion

The purpose of this study was to compare the effects of Hylan G-F 20 injections on knee osteoarthritis, separated by knee compartment and grade. The main findings in the study included a significant reduction in pain and better function in the activities of daily life and symptoms in patients with grade III and grade IV lateral compartment knee osteoarthritis. Statistically significant increases in KOOS pain scores, meaning they experienced less pain, was seen in all patients except in patients with grade II lateral and medial compartment knee OA. An increase in scores in the KOOS category of symptoms category was also seen in patients with grade II and III patellofemoral OA.Similar improvements in knee pain, symptoms, and function have been documented in patients with OA treated with HA injections [14-16].

The 2nd edition of the Academy of Orthopaedic Surgeons guideline on treatment of knee OA released a position statement claiming that “we cannot recommend using HA for patients with symptomatic knee OA”, based on a lack of clinically important improvement [17]. The Osteoarthtitis Research Society International guideline for non-surgical management of knee OA also stated that the recommendation for HA injection was uncertain because of the inconsistent conclusions among the meta-analysis and conflicting results regarding the safety of HA [18]. In contrast, hylan G-F 20 has been shown to give greater improvement than placebo injection in patients [19]. HA injection has been shown to decrease knee pain from a time span of 6 month to a year and can also be used in combination with knee rehabilitation to reduce knee pain at night [16,20,21]. Viscosupplementation has also been proven effective in the treatment of not only knee OA, but shoulder gleno-humeral OA [22]. HA’s effects can be due to its intrinsic anti-inflammatory characteristics and its increase in knee viscosity [23,24]. Lower adverse effects are also seen in patients with HA injections [25].

There were a few limitations to this study. Many patients did not fill out post injection surveys and had to be excluded from this study. Since this is a retrospective study there may have also been some recall bias from the patients. We did not include parameters such as length of HA injection effect in this study or the amount of time it took for the patient to feel the effects of the injection. Also, many patients of our mean cohort age (60) do not engage in many rigorous sports activities and did not fully complete the sports and recreation or knee related quality of life portion of the KOOS survey.

Conclusion

This retrospective study showed that intra-articular injection of Hylan G-F 20 was most effective in providing statistically significant pain relief, and better knee function in everyday activities in patients with grade III and grade IV lateral compartment knee osteoarthritis.HA injection was also very effective in reducing the knee pain in the majority of patients.

Table 1: Mean +/- SD baseline and 6 week follow-up KOOS scores of patients with grade II-IV patellofemoral OA.

Note: KOOS consists of five subscales: symptoms, pain, activities of daily living, sports and recreation function, and knee-related quality of life.

Table 2: Mean +/- SD baseline and 6 week follow-up KOOS scores of patients with grade II-IV medial compartment OA.

Note: KOOS consists of five subscales: symptoms, pain, activities of daily living, sports and recreation function, and knee-related quality of life.

Table 3: Mean +/- SD baseline and 6 week follow-up KOOS scores of patients with grade II-IV lateral compartment OA.

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