Viscosupplementation for Osteoarthritic Knees
(!!!) Osteoarthritis (OA) affects millions and is the leading cause of pain and discomfort worldwide. To help patients struggling with OA, physicians use viscosupplementation to assist patients back to their pre-arthritic lives. This method of treatment is used after the use of anti-inflammatories and physical therapy fail to help. There are multiple brands of viscosupplementation offered as well as evidence-based research proving the benefits it has in treating osteoarthritis.
Biology
Viscosupplementation was introduced to break the cycle of progressive osteoarthritis. Hyaluronic acid is a natural substance that is found in the synovial fluid and joint cartilage around the knee that acts as a lubricant and shock absorber. As the knee starts to develop osteoarthritis, the hyaluronic acid starts to break down and dilute, reducing its natural properties and increase the inflammatory process. Viscosupplementation consists of intra articular injections of hyaluronic acid into the knee capsule to replace the ineffective synovial fluid and serve as a healthy lubricant (McArthur, Fabricant & Gonzalez Della Valle, 2012).
Types of Viscosupplementation
There are multiple different brands of viscosupplementation used by physicians to treat knee OA. There are currently six approved: Hyalgan, Synvisc-One, Supartz, Orthovisc, Euflexxa, and Gel-One. Each has a different protocol and molecular weight and can have different effectiveness rates for different individuals (Cuevas-Trisan, 2016). At my field experience at Lancaster Orthopedic Group, we only used Synvisc and Euflexxa with our patients.
Hyalgan. Hyalgan was the first viscosupplementation form approved by the FDA in 1997. It is a solution that contains hyaluronate that has been taken from the combs of chickens. It is an injection regimen approved for five weekly intervals, however, some patients get benefit from it with three injections given at weekly intervals (Hyalgan, 2018).
Synvisc. Synvisc was the second form of viscosupplementation to be approved by the FDA in 1997 and is made from the combs of chickens (Synvisc-One, 2016). It is composed of two hylan polymers, Hylan A, a soluble molecule, and Hylan B, an insoluble gel consisting of an uninterrupted crosslinked network. This crosslink creates Hylan GF-20. Synvisc is a series of three injections, one per week for three weeks, which effects lasting for up to six months (Stitik & Kim, 2008). There is another form of Synvisc out called Synvisc-One that is a single-injection rather than three (Synvisc-One, 2016).
Supartz. Supartz was approved for use in 2001 and is comparable to Synvisc. This solution of highly purified hyaluronic acid is also extracted from the combs of certified chickens. The patients receive a max of five injections given at weekly injections, however, some only need to receive three. Pain relief starts after the first shot and lasts up to six months (Supartz FX, 2015).
Orthovisc. Orthovisc was approved in 2004 and is a viscous mixture of highly purified hyaluronic acid from the combs of chickens. Patients who opt for this form of viscosupplementation receive a total of three or four injections, one a week. The number of injections varies because some patients react sooner and feel better with only three (Orthovisc High Molecular Weight, 2017).
Euflexxa. Euflexxa was FDA approved in 2004 and is made in a controlled environment. This treatment involves 3 injections given weekly. With this form, it is possible to start feeling relief after the first injection, but the patient should return to get the next two injections for the full benefit. The relief from this form normally starts after the third injection and lasts up to six months (Euflexxa, 2017).
Gel-One. Gel-One was the last to be approved in 2004 and is cross-linked hyaluronate. This form is also extracted from the combs of chickens and highly purified. Gel-One is the first to offer a single-injection treatment with effects lasting up to six months (Gel-One, 2018).
Process
Viscosupplementation injections require precision. It is recommended that only trained physicians perform these injections because the gel must be injected directly into the small space of the knee that contains the joint fluid and articular cartilage. If the hyaluronic acid misses the joint capsule and enters the soft tissue that surrounds the knee joint, the patient has the possibility of experiencing uncomfortable side effects (Vad, 2013).
These injections typically take less than five minutes. The patient can either lie down or sit with their knees at 90 degrees. The knee is wiped down with an alcohol pad and then sprayed with a freeze spray to remove the initial sting of the needle. Once the patient is relaxed topically numb, the gel is injected. In the case where the patient has an effusion, lidocaine is first injected into the knee, followed by an aspiration of the fluid before the hyaluronic acid injection is given (Vad, 2013).
Evidence-Based Medical Research
Initial Discovery
The earliest viscosupplementation clinical trials were performed on racehorses with painful osteoarthritis, and then in the early 1970s, the trials extended to include use on humans. Scientists reported in both humans and horses, there was longer lasting analgesic effects than the residence time of hyaluronic acid injections into the knee joint. It was later discovered that the elastoviscous properties of solutions being injected were important factors in reducing pain due to nerve activity in cats and rats, both healthy and inflamed joints. It was also proved around the same time that the hyaluronan solutions in animal arthritis models can stimulate the healing of intra-articular wounds after a trauma. Then in the 1980s, preparations of the solutions that varied greatly in molecular weights but had the same concentrations were introduced as viscosupplementation-based therapeutic agents by imitating pathological synovial fluid. Eventually, researchers adjusted the hyaluronan solution to be what is used today and have it available worldwide, however, there are no standards in that the elastoviscous properties and dosages vary (Balazs, 2004).
Safety and Efficacy
Safety. With any procedure, the safety and efficacy need to be taken into account. There have been numerous studies outlining the details of the safety of hyaluronic acid injections. However, in an article in the US National Library of Medicine, Benjamin McArthur states that it is important to note that nearly all the trials evaluating the safety of viscosupplementation are funded by the pharmaceutical industry, therefore, bias may be introduced into the interpretation of the results. With that being said, there have been no major systemic safety issues detected by patients and researchers during trial periods, but there has been an occurrence of a local reaction at the injection site. This reaction was found to be mild and self-limited and normally resolved itself in a few days (McArthur, Fabricant & Gonzalez Della Valle, 2012).
In a few cases, however, another form of inflammatory response called “pseudosepsis†was seen typically after repeated injections. The exact pathogenesis is not known; however, there is growing evidence that suggests an immune-mediated etiology is the cause. The evidence was found in preclinical and clinical studies that measured the production of Hylan antibodies and how prevalent immune cells are in the joints of pseudoseptic patients (Goldberg, & Coutts, 2004).
Efficacy. The efficacy of hyaluronic acid injections has been widely supported in literature, however, due to publication bias and some limitations in low trial quality, the effectiveness needs to be viewed with some skepticism. The authors of Cochrane review in 2009 stated that viscosupplementation is effective in the treatment of knee OA with benefits of pain relief, better function at the joint, and decreasing the risk of further damage. Skepticism is introduced when the report reveals that the clinical effect is product-dependent, and there were few randomized studies that made direct comparisons of the different viscosupplementation types difficult (McArthur, Fabricant & Gonzalez Della Valle 2012).
There was a study performed in order to review the efficacy of a single injection versus multiple injections. The study was conducted by a group who studies musculoskeletal disorders who measured the mean score for knee pain at 3 months or 6 months. Overall, the hyaluronic acid injections were effective in relieving keen pain. It found that two to four injections yielded the best effect at both three months and six months. A single injection, however, produced a non-significant effect at both three and six months. Overall, the greatest effectiveness of the hyaluronic acid was seen between 2-4 injections, max of five, showed the most improvement with osteoarthritic knee pain relief (Concoff, Sancheti & Shaw, 2017).
Ideal Candidate
While the ideal candidate has not been clearly defined for viscosupplementation, the majority of the patients who participated in clinical studies and receive the injections are over the age of 60 who have moderate to severe arthritis. However, a recent analysis discovered that patients over the age 65 who suffer from more diseased states like complete loss of the joint space are less likely to respond to the hyaluronic acid injection as a younger patient with healthier joints (McArthur, Fabricant & Gonzalez Della Valle 2012). For each patient, however, the response to viscosupplementation cannot be anticipated as it is different for each individual (Boyer, 2015).
Trials
Hyaluronic Acid vs. Corticosteroids. In a randomized double-blind trial, 140 patients who complain of knee OA pain, were followed for 12 weeks after being randomly chosen to receive either an injection of hyaluronic acid or corticosteroid. The qualifications for the selected patients were based on age, radiographic OA grade of II-III and osteoarthritis pain for at least three months. Excluded patients included those who had a history of trauma, infections, surgery, cancer, or sores on the targeted knee, use of NSAIDs two days prior to the trial, or any injections to the knee within the last six months. Pain levels were monitored and recorded throughout the 3 months. Before the intervention with the injections, the mean pain score for the corticosteroid group was 7.152.01, which was close to the hylan group which was 7.522.17. At the end of the first month, the corticosteroid group had decreased to 5.692.33. At the end of the second month, an increase to 5.902.33 was seen and again increased at the end of the third month to 6.562.15. This pain score was found to not be statistically different from the primary. The hylan group’s results at the end of the first month decreased 6.632.03, continued to decrease at the end of the second month with scores of 6.432.01, and then further decreased to 6.702.01. These results were significantly lower than the starting pain score (Bannuru, Natov, Obadan, Price, Schmid & McAlindon, 2009).
From the results found, it was concluded that the patients in the trial received pain relief from both the hyaluronic acid and corticosteroid injections during the first and second months compared to the primary pain recorded. However, the pain reduction was more evident in the HA injection during the third month than with the corticosteroid. Researchers in this trial were then led to the conclusions that CS injections have a pain relief duration of less than three months, whereas the durability of the HA injection for pain relief would last beyond three months (Bannuru, Natov, Obadan, Price, Schmid & McAlindon, 2009).
Future Directions
Viscosupplementation in knee osteoarthritis has had significant results that have led researchers to look into the possible roles intraarticular hyaluronic acid injection could have on other arthritic joints. As of now, the FDA only approved its use for knee osteoarthritis, however the use on a painful shoulder, ankle, and hip arthritis. Other areas have conflicting data on whether or not it would be more beneficial or harmful, like the use of HA for trapeziometacarpals. Along with this, these injections have been found to slow the degeneration of the cartilage in the joints, tissue repair, and in some cases even slow the progression of diseases (journals). Due to the efficacy of viscosupplementation with osteoarthritis of the knee, the use of it in other pathologies that affect the knee is possible in additional patient populations (Strauss & Miller, 2009).