Hyalgan, Synvisc, Supartz
New Non-Operative Treatments for Osteoarthritis
One of the biggest changes in management of osteoarthritis was first FDA approved in January 1997. This treatment was hyalgan and synvisc injections. What is this treatment and how did it originate? Will it work for you? What other non-operative treatments are available? What is on the horizon in the next five to ten years? Will knee replacements ever become obsolete? If you have these questions or more, then this article is for you.
Hyalgan is in the class of hyaluronan compounds. There are at least two others, including synvisc and supartz. These compounds are made up of different molecular weights of hyaluronase which is a natural compound found in all knees. Hyaluronase has several important functions in synovial fluid (fluid within the knee and other joints). First, it is a lubricant that reduces the friction between the femur (thigh bone) and tibia (leg bone). These bones make up the hinged joint we know as the knee. Second, it inhibits certain enzymes that break down articular cartilage in the joints. Third, it acts as an anti-inflammatory agent within the joint. Fourth, it inhibits pain. There are probably other mechanisms as well and these are being studied.
By protecting the cartilage and preventing it from being broken down, it changes the metabolism within the knee joint from one that is catabolic (breaking down cartilage) to anabolic (building up cartilage). Early studies in well established journals have shown cartilage regeneration within treated joints. The hyalgan is placed in the knee in a series of five injections completed over a four to five week period. After it is injected into the knee, utilizing a local anesthetic, it is reabsorbed from the knee within 24-48 hours. This leads to the next question. If it is absorbed that quickly, why does it work for six months or even one year? To answer this question we need to go back to the original patents for both hyalgan and synvisc which were being developed at the same time in competition with one another. Initially, it was thought that the compounds worked because they lubricated the knee joint, like oiling a motor. Because this was the current thinking at the time of development, synvisc was made by cross-linking hyaluronase molecules using formaldehyde to form a compound with an average molecular weight of 6 million daltons. Natural hyaluronase within the knee has a molecular weight of up to 10 million daltons but is present in various sizes (polydisperse species). The synvisc manufacturer thought they were on to a good thing by patenting the process for cross-linking to form a larger molecular weight and in fact synvisc lasts in the knee up to one week after it is injected. Hyalgan, on the other hand has a molecular weight of 500,000 to 730,000 daltons so it is absorbed faster in one to two days. Synvisc is given with only three injections and initially hyalgan with five, so at first synvisc was thought to be superior. Hyalgan can now be given in three injections also. Later research showed some interesting revelations. Clinical studies gave important information which informed doctors about the mechanisms of action. As it turns out as researchers further investigated, they found out that hyaluronase compounds work by binding to receptors of type B synovial fibroblasts. These are the cells lining the knee joint (and other joints). When they bind to the receptors, a positive feedback loop is initiated and the fibroblasts start to generate hyaluronase on their own. This was very important in understanding how osteoarthritis actually progresses. As people develop osteoarthritis either from an injury and hereditary causes, the knee senses the injury and enzymes are released in to the knee to fight the injury. These enzymes break down hyaluronase and cartilage starting a downward spiral. As osteoarthritis progresses there is less and less hyaluronase within the knee and the arthritis progresses faster. The best molecular weight for receptor binding is about 500,000 to 730,000 Daltons the same molecular weight as hyalgan. This means that hyalgan works more directly on the positive feedback loop within the knee to reverse the catabolic pathways. Also, with synvisc, there is a 7.2% incidence of severe inflammatory reactions per series. This may be due to the higher molecular weight of synvisc. Synvisc because of its higher molecular weight does not initiate endogenous hyaluronase production very well and its mechanisms of action are more unclear than hyalgan. Because hyalgan works on the lining of the knee and indirectly on the articular cartilage, it can work quite well even in a very arthritic knee. In fact it works about 80-85% of the time according to the literature. I have never seen any side-effects in the nine years I have been using it. This should be good news to anyone comtemplating a knee replacement, because it gives them a non-operative alternative and one that does not burn any bridges. On the other hand, once one undergoes a knee replacement, that person crosses the bridge and torches it, there is no going back and the only alternative to a failed knee replacement is another knee replacement.
What other non-operative treatments are available? In the year 2002 the number one recommendation for treatment of osteoarthritis from the ACR ( American College of Rheumatology) was quadriceps strengthening. Another dietary supplement available is called Cosamin-DS. This consists of glucosamine and chondroitin sulfate. Not all glucosamine brands are the same because they are not FDA regulated. Cosamin-DS is the only brand that has been studied numerous times in the orthopedic literature and shown to work. It has been shown to be effective about 80% of the time in relieving pain. It takes thee months to work, so don't be impatient.
On the horizon is DNA and genetic engineering which in the future may allow the entire surface of the knee to be regenerated with shiny new articular cartilage.
The decision is yours, non-operative versus operative, wait or don't wait. See your regular doctor if you have any other questions or need more information.