| | | Animal-based | Glucosamine / Chondroitin Sulfate
 | A scientific review released by HHS' Agency for Healthcare Research and Quality (2007) concludes that evidence of benefit is lacking for many common ways of treating osteoarthritis of the knee, including popular dietary supplement ingredients, a common surgical procedure, and injected preparations.
The review found that glucosamine and chondroitin, over-the-counter dietary supplement ingredients that are used widely because of their purported benefits to relieve knee pain caused by osteoarthritis and improve physical functioning, appear to be no more effective than placebos. A placebo is a harmless substance given to selected patients in a clinical trial that looks like the real drug or injection being studied, but which has no medical effect.
The review, which was requested and funded by HHS' Centers for Disease Control and Prevention, also failed to find convincing evidence of benefit from arthroscopic surgery to clean the knee joint with or without removal of debris and loose cartilage.
Published studies generally report that injections with hyaluronan preparations (substances that are intended to improve lubrication of the knee joint) improve scores on patient questionnaires used to measure pain and function. However, the evidence is uncertain because of variation in study quality and difficulty determining whether changes in scores translate into real clinical improvements for patients.
"Millions of Americans seek relief from the pain and reduced mobility caused by osteoarthritis of the knee," said AHRQ Director Carolyn M. Clancy, M.D. "However, they should work with their clinicians to decide the best course of treatment for them based on what has and has not been proven to work."
Osteoarthritis is a widespread, costly disease that wears away the cartilage cushioning the knee joint, causing pain and reducing mobility. Arthritic diseases, which include osteoarthritis, affect an estimated 46 million people in the United States, and at age 64 and older, one in 10 Americans is estimated to have osteoarthritis of the knee. Osteoarthritis and related arthritic conditions cost more than $81 billion a year in medical care, lost wages, and other expenses.
The authors, who were led by David J. Samson, M.S., associate director of the AHRQ-supported Blue Cross and Blue Shield Association Evidence-based Practice Center in Chicago, reviewed findings from 53 randomized clinical trials of glucosamine, chrondroitin, and injections with hyaluronan preparations and 23 studies of arthroscopy. The review scrutinized individual studies concerned with these treatments' effects as well as meta-analyses that analyzed the combined evidence of groups of studies.
According to authors, better quality randomized clinical trials are needed to clarify whether these treatments are beneficial. However, given the aging of the population and increasing prevalence of obesity - both risk factors for osteoarthritis of the knee - "research on new approaches to prevention and treatment of osteoarthritis of the knee should be a high priority."
There was a study done using a prescription preparation of hyaluronan (pronounced hyal-u-ROE-nan). For more about the positive results, please see the link between Knee Pain and Hyaluronic Acid.
A two-year study was conducted called the Glucosamine-chrondroitin Arthritis Intervention Trial (GAIT) to know whether glucosamine was effective or not. And now, the results are in. GAIT measured the effects of taking glucosamine alone, chondroitin alone, a glucosamine-chondroitin combination, and celecoxib alone against placebo in 1,583 people with either mild or moderate-to-severe pain from knee OA.
Results show that the combination of glucosamine and chondroitin is better than placebo, but the benefits appear to depend on pain severity.
Mild pain. The glucosamine and chondroitin combination did not show effectiveness for people with mild pain. Sixty-three percent of those with mild pain responded to the glucosamine and chondroitin combo, and 62 percent responded to the placebo.
Moderate-to-severe pain. Of the people with moderate-to-severe knee OA pain, 79 percent who took the glucosamine-chondroitin combo experienced pain relief, compared with 66 percent who took glucosamine alone, 61 percent who took chondroitin alone, and 54 percent who took placebo. “The people with moderate-to-severe pain who took glucosamine and chondroitin sulfate together showed significant improvement in their knee pain,” says lead author Daniel O. Clegg, MD, professor of medicine and chief of the division of rheumatology at the University of Utah School of Medicine in Salt Lake City, one of 16 rheumatology centers involved in the NIH-sponsored GAIT.
The results of a second smaller trial, called the GUIDE trial, are also in. Conducted in Spain and Portugal, the six-month-long study measured the effects of a 1,500-mg daily dose of glucosamine against a 3,000-mg daily dose of acetaminophen (Tylenol) or placebo in 318 people with knee OA. The researchers concluded that glucosamine relieved pain significantly better than the acetaminophen or placebo. |
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Diet |
Weight Loss
 | Very attainable weight loss goals are sufficient to reduce pain and therefore motivate overweight patients with knee osteoarthritis to keep that weight off, according to research presented (November 13, 2006) at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.
Weight gain dramatically multiplies the pounds of pressure and loading forces on the knee structure. Because this pressure leads to more wear and tear over time, body weight is considered one of the significant contributors to the onset and progression of knee osteoarthritis. Conversely, weight loss can relieve those realities.
Now, a long-term weight loss program has demonstrated that even modest weight loss contributed to improved quality of life in 30 mildly obese patients, and the resulting reduction in pain was so dramatic as to motivate their keeping the weight off. |
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Drug |
Conventional Drugs / Information
 | Please see the link between Knee Pain and Hyaluronic Acid. |
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Physical Medicine |
Physical Supports
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Skin |
DMSO Topically
 | Double-blind and other controlled studies have found a 25% DMSO gel effective for pain relief in osteoarthritis of the knee. |
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Surgery/Invasive |
Prolotherapy
Hyaluronic Acid
 | Physicians have injected hyaluronic acid directly into the synovial fluid in the knee as a treatment for osteoarthritis for the last 20+ years. There are many peer-reviewed articles written on the use of hyaluronic acid for this purpose. Please see the link between knee pain and Glucosamine.
In a meta-analysis of eight hyaluronan trials involving 971 patients, outcomes in patients treated with hyaluronan were superior to outcomes in patients treated with placebo at the end of the treatment cycles and after six months. [Ann Rheum Dis 1998;57:pp. 637-40]
Treatment is expensive. For a package of three prefilled syringes of Synvisc, the average wholesale price is $620.00. Third-party reimbursement is variable, but Medicare and most insurance companies now cover viscosupplementation. A product called Synvisc-One is now available which achieves a similar result in just one injection.
A study of Synvisc-One (hylan G-F 20) was conducted in 253 patients in six countries outside the United States. Patients were at least 40 years old, had mild or moderate knee OA and were experiencing moderate to severe knee pain. Patients in the study were given either:
•A single injection of Synvisc-One •An injection of salt water (called a "saline control")
The goal was to determine how well Synvisc-One reduced knee pain during five common activities (walking, going up stairs, etc.). Doctors evaluated the patients at weeks 1, 4, 8, 12, 18 and 26.
Results: The study showed that patients who received Synvisc-One had significantly less pain over six months and felt significantly better than the saline control group. Specifically, 71% of patients reported pain relief with Synvisc-One. Most patients reported pain relief starting at week four.
Side effects were also tracked. The types and frequencies of side effects were similar between the two groups. The most common side effects were knee pain, stiffness, and swelling or fluid buildup in or around the knee. These were generally mild to moderate and did not last long. Other side effects, such as rash, may also occur. Side effects were generally mild to moderate and did not last long. No serious side effects were seen in the injected knee during the study that were related to the use of Synvisc-One.
Before trying Synvisc-One or SYNVISC, tell your doctor if you are allergic to products from birds—such as feathers, eggs or poultry—or if your leg is swollen or infected. Synvisc-One and SYNVISC are only for injection into the knee, performed by a doctor or other qualified health care professional. Synvisc-One and SYNVISC have not been tested to show pain relief in joints other than the knee.
Synvisc-One is the same formulation as SYNVISC. The only difference is that Synvisc-One is provided with one injection, compared to the three injections required for SYNVISC. Both treatments can provide up to six months of pain relief.
Here is the home page of this product. This one-time injection costs upwards of $400.00 wholesale, so prolotherapy should be considered for those who can not afford this.
An FDA review of this product, also called Genzyme, at that time, can be found here. |
Surgery
 | A review in 2007, which was requested and funded by HHS' Centers for Disease Control and Prevention, failed to find convincing evidence of benefit from arthroscopic surgery to clean the knee joint with or without removal of debris and loose cartilage. |
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