Discussing the viability of viscosupplementation within the clinician’s armamentarium for treating osteoarthritis (OA) knee pain, this author surveys the literature and draws upon her clinical experience with a review of pertinent case studies.

Osteoarthritis (OA) affects approximately 49 million Americans, according to the National Institutes of Health (NIH). Projected estimates from the NIH suggest that OA will affect 72 million Americans by the year 2030.¹

There are many different treatment options clinicians can utilize to help patients achieve pain relief (see “A Stepwise Approach To Managing OA Knee Pain” below). Treatment modalities range from lifestyle modifications and physical therapy to nonsteroidal antiinflammatory drugs (NSAIDs), intraarticular injections and surgical options.

Where does viscosupplementation fit into the armamentarium of treatment options for OA knee pain? Before one understands the role of viscosupplementation, one must first have a strong grasp of the degenerative process of OA in the knee.

Understanding The Pathophysiology Of The OA Process
At the end of the distal femur and proximal tibia, the articular cartilage is comprised of chondrocytes. Water accounts for 65 to 85 percent of the makeup of chondrocytes, which interact with proteoglycans, collagens, hyaluronic acid and other material.^3,4 The complex cellular process of OA includes changes to the articular cartilage and synovial fluid. In essence, OA involves the imbalance of matrix synthesis and matrix degradation.⁵

Researchers believe the process of articular cartilage degradation of the knee occurs over time due to gradual stresses such as increased force in weightbearing, microfractures in the subchondral bone and trauma. Other possible causes may include aging, metabolic diseases, inflammation and immune system malfunctions.⁶

Osteoarthritis may lead to further changes such as stiffening of the subchondral portion of the knee joint as well as the development of osteophytic and subchondral cysts.^2-4 The synovium subsequently becomes thickened and inflamed. The tendons that surround the joint become thickened, ligaments are strained and this leads to a stiff, contracted knee joint.^3,5

All five viscosupplement agents available in the U.S. differ in weight, physical properties, the duration of effect and frequency of injections.

As noted above, part of the cellular matrix of the knee includes a large molecule of hyaluronic acid. These molecules form a structural network that provides knee cartilage with the critical properties of compressibility and elasticity.² Hyaluronic acid is also present in the synovial fluid and facilitates the highly viscous lubrication of the synovial joint.^3,7

A Closer Look At The Pros And Cons Of Viscosupplementation
Injections of hyaluronic acid via viscosupplementation agents reportedly improve shock absorption and lubrication properties of the synovial joint. The prevailing thinking is that viscosupplementation provides immediate pain relief and facilitates long acting functions such as joint homeostasis. Joint homeostasis is an extremely important factor in the effectiveness of viscosupplementation. Joint homeostasis restores trans-synovial flow, which aids in the return of joint mobility and enhances metabolic and rheologic homeostasis of the knee joint.^3,4

A Stepwise Approach To Managing OA Knee Pain

At a cellular level, hyaluronic acid also offers the following benefits:
• enhancing the synthesis of proteoglycans and extracellular matrix proteins;
• altering the profile of inflammatory mediators and the expression/activity of matrix-degrading enzymes;
• acting as an antioxidant; and
• affecting immune cells by modulating leukocyte function.^3,4

That said, there are potential risks to viscosupplementation. These risks include joint effusion, joint swelling, arthralgia, joint warmth and injection site erythema.3,7 Contraindications for viscosupplementation include avian or chicken product allergy, joint infection, joint hemarthrosis and skin infection.^3,7

There are currently five viscosupplement agents available in the United States for the treatment of OA knee pain. These agents include:
• One percent sodium hyaluronate (Euflexxa, Ferring Pharmaceuticals);
• Sodium hyaluronate (Hyalgan, Sanofi Aventis);
• High molecular weight hyaluronan (Orthovisc, DePuy/Mitek);
• Sodium hyaluronate (Supartz, Smith and Nephew); and
• Hylan G-F 20 (Synvisc, Genzyme).

These products differ in terms of weight, physical properties (bacterial versus rooster combs), and the duration of effect. They also differ when it comes to the number of injections. There are three injections to the series for Synvisc and Euflexxa whereas there are three and five injection series options available for Hyalgan and Supartz. One can administer Orthovisc in a three- or four-injection series.

The author emphasizes using a sterile technique when preparing for a viscosupplement injection.

A Guide To The Viscosupplementation Procedure
After obtaining informed consent from the patient for viscosupplementation injections, one should ensure that he or she has the following supplies for the procedure:
• a 23- to 25-gauge needle for appropriate anesthesia;
• appropriate anesthesia such as lidocaine;
• topical methyl chloride;
• betadine and alcohol for antiseptic technique;
• a 22-guage, 1.5-inch needle for the viscosupplementation injection; and
• the viscosupplement agent of choice.

In regard to the procedure itself, clinicians should:
• review the informed consent with the patient;
• ensure the patient is in a supine position;
• keep needle products out of the patient’s view in order to avoid a vagal response;
• ensure strict aseptic technique;
• administer the appropriate anesthesia (either injectable or topical);
• use the injection approach of choice (I commonly use the lateral approach); and
• proceed to inject the viscosupplement agent using the same needle procedure as the anesthesia administration. (Always make certain the knee joint is apirated for any effusion before using the same needle approach.)

Case One: When An Athlete Seeks To Remedy Knee Discomfort
Interestingly enough, one meta-analysis found that viscosupplementation was more effective in young men with less severe degenerative joint disease than in patients over the age of 65 who had more “severe” radiographic changes.⁸ Let us take a closer look at a variety of clinical presentations of knee OA and the use of viscosupplementation via injections of hylan G-F 20 to help facilitate pain relief.

A 35-year-old man presents to our clinic with OA in his right knee. The weekend warrior athlete states that he noticed pain in the knee a few years ago and reports swelling, morning stiffness and pain when climbing stairs.

It is useful to provide a visual explanation of the pathophysiology of OA of the knee prior to performing a viscosupplementation procedure.

The patient’s primary care physician had emphasized physical therapy, NSAIDs, orthotics and ordered magnetic resonance imaging (MRI). While physical therapy and NSAIDs helped with the muscle imbalance issues and the swelling respectively, the patient says he is not “where I want to be with sports” and still is experiencing discomfort when climbing stairs. The patient directly asks about viscosupplementation and emphasizes that he wants to be “as active as possible for as long as possible without pain pills and surgery.”

The patient also notes a soccer injury from high school, explaining that he previously had a medial collateral ligament (MCL) injury and mild anterior cruciate ligament (ACL) sprain when he was 17. The injuries had been treated conservatively and the patient had no problems until a couple of years ago when his knee pain surfaced.

After obtaining a complete history and physical, X-rays, a repeat MRI and lab studies, we concluded the patient was dealing with mild grade one to two degenerative changes of his patellofemoral joint and at his medial joint line. We found no other pathology during the diagnostic workup.

The combination of appropriate shoe wear and orthotics addressed the mechanical issues nicely, and physical therapy had addressed muscle imbalance. The laboratory data did not reveal any type of inflammatory process and the MRI was negative in terms of a mechanical meniscus tear or cruciate ligament injury.

We administered hylan G-F 20 injections over three office visits and the patient tolerated the procedure well. There were no side effects. In a follow-up visit six weeks later, the patient says he feels great, is excited about the results and eager to progress back to his activity level albeit at a slower rate. He notes that he is trying to avoid excessive stair climbing and has decided to eliminate sports that require cutting, planting and pivoting of the knee.

Case Two: Can Viscosupplementation Delay Surgery?
Some studies suggest that viscosupplementation may assist in delaying joint arthroplasty surgery.⁹ Indeed, an orthopedic surgeon colleague referred such a patient to our clinic and asked me to evaluate her as a possible candidate for viscosupplementation.
The 43-year-old woman presented with persistent knee pain one year after undergoing a menisectomy and arthrofibrosis resection. She had been involved in a motor vehicle accident, which had precipitated the multiligamentous surgery.

The patient has known grade three to four OA changes of her distal femur condyle and patellofemoral joint. She continues to experience persistent knee pain despite a multi-modal treatment plan including physical therapy, knee bracing, orthotics and corticosteroid injections. She is very frustrated with the knee pain.

What A Survey Of MCOs Reveals

Plain X-rays reveal mild to moderate degenerative joint disease in all three compartments. Arthroscopic findings reveal significant cartilage thinning throughout the medial compartment with grade three thinning throughout the medial femoral condyle and grade one changes in the medial tibial plateau. Additionally, the patient has grade one changes under the surface of the patella and there is a 1.5 by 1.5 cm grade three to four lesion in the central trochlear groove. No MRI is needed.

Peripheral laboratory data reveals no evidence of infection. The patient has a normal white blood cell count, sedimentation rate and C-reactive protein. Pathology reports from surgery reveal no concerning features other than normal meniscus tissue. She is moderately overweight with stable anemia.

After obtaining a thorough patient history and performing a thorough physical exam, we determined the patient had no contraindications to viscosupplementation. We proceeded with a trial of hylan G-F 20. The patient tolerated the procedure well for three consecutive visits and no side effects occurred.

During a follow-up visit approximately six to eight weeks after her last injection, the patient notes she has “mild to moderate” pain relief in her knee but continues to have moderate pain when climbing stairs. We will continue to counsel her regarding lifestyle modification and monitor her progress over the next several months.

Case Three: When Significant Comorbidities Prevent Surgery
An 84-year old, frail woman presents with moderate to severe OA in the knee. She has multiple comorbidities including hypertension, non-insulin dependent diabetes mellitus (NIDDM), gastroesophageal reflux disease (GERD), hyperlipidemia, cerebrovascular accident (CVA) and chronic obstructive pulmonary disease (COPD). She is not a candidate for joint arthroplasty.

Her primary care provider has referred her for conservative treatment of bilateral knee pain and consideration for viscosupplementation. The patient and her family are eager to pursue the procedure.

The patient’s various conditions are stable. Her list of current medications includes: aggrenox, acetylsalicylic acid, albuterol, atrovent, glucophage, nifedipine, Ultram and Zocor. The patient has allergies to codeine, vancomycin HCL, lisinopril and hydrochlorothiazide.
The patient has a comprehensive treatment plan in place for moderate to severe OA that includes lifestyle modification, physical therapy, bracing, the use of an assistive device and corticosteroid injections.

(Photo courtesy of Michael O’Brien, MD, BIDMC) Here one can see a superior lateral approach to viscosupplementation injection of the knee.

Radiographs reveal severe bilateral medial knee joint OA with subchondral changes, loose bodies and severe degenerative patellofemoral osteophytes. After a thorough history and physical exam, we determine the patient has no contraindication to viscosupplementation and proceed with a trial of hylan G-F 20.

The patient tolerates the procedure well for three consecutive visits and no side effects occur. At a follow-up visit approximately six to eight weeks after the last injection, the patient had no relief of her pain. We continue to support this patient with corticosteroid injections every three months as needed, the use of Ultram and an emphasis on lifestyle considerations as well.

Final Notes
Viscosupplementation is a viable, safe treatment option for patients with OA of the knee, especially when surgery is not an option and conservative treatment is recommended. Researchers are currently doing exciting work with viscosupplementation in terms of evaluating the frequency of injections, the duration of pain relief and long-term effects. Researchers are also studying the potential use of viscosupplementation for OA of the hip, the carpometacarpal (CMC) joint and ankle.

Viscosupplementation can be a useful adjunctive modality in a variety of clinical presentations when it comes to OA of the knee. In the aforementioned case studies, the younger male patient with mild osteoarthritic changes appears to “clinically” do better with viscosupplementation. These cases seem to mirror the available literature on viscosupplementation thus far.¹ However, it is important to note that researchers have shown post-injection efficacy for anywhere from five to 13 weeks after treatment.^8,9 Therefore, additional time and assessment with cases similar to the last two may reveal additional effect up to 13 weeks after injection.

Editor’s note: For a related article, see “Joint Injections: Key Clinical Pearls To Maximize Outcomes” in the March 2006 issue of Arthritis Practitioner.