Saturday, January 31, 2009

Supplements no better than placebo

Supplements no better than placebo in slowing cartilage loss in knees of osteoarthritis patients

In a two-year multicenter study led by University of Utah doctors, the dietary supplements glucosamine and chondroitin sulfate performed no better than placebo in slowing the rate of cartilage loss in the knees of osteoarthritis patients.
This was an ancillary study concurrently conducted on a subset of the patients who were enrolled in the prospective, randomized GAIT (Glucosamine/chondroitin Arthritis Intervention Trial). The primary objective of this ancillary study was to investigate whether these dietary supplements could diminish the structural damage of osteoarthritis. The results, published in the October issue of Arthritis & Rheumatism, show none of the agents had a clinically significant effect on slowing the rate of joint space width loss —the distance between the ends of joint bones as shown by X-ray.
However, in line with other recent studies, the researchers observed that all the study's participants had a slower rate of joint space width loss than expected, making it more difficult to detect the effects of the dietary supplements and other agents used in the study.
Rheumatologist Allen D. Sawitzke, M.D., associate professor of internal medicine at the University of Utah School of Medicine, was lead investigator. "At two years, no treatment achieved what was predefined to be a clinically important reduction in joint space width loss," Sawitzke said. "While we found a trend toward improvement among those with moderate osteoarthritis of the knee in those taking glucosamine, we were not able to draw any definitive conclusions."
More than 21 million Americans have osteoarthritis, with many taking glucosamine and chondroitin sulfate, separately or in combination, to relieve pain. The original GAIT, led by University of Utah rheumatologist Daniel O. Clegg, M.D., professor of internal medicine, was a multicenter, randomized, national clinical trial that studied whether these dietary supplements provided significant pain relief to people with osteoarthritis in the knees. GAIT found that the supplements produced no more pain relief than placebo (New England Journal of Medicine, February 2006), although a subset of the original GAIT participants with moderate to severe osteoarthritis knee pain appeared to receive significant pain relief when they took a combination of glucosamine and chondroitin sulfate.
In this ancillary study, GAIT patients were offered the opportunity to continue their original study treatment for an additional 18 months, for a total of two years. Participants remained on their originally assigned GAIT treatment: 500 mg of glucosamine three times a day; or 400 mg of chondroitin sulfate three times a day; or a combination of the two supplements; or 200 mg of celecoxib daily; or a placebo.
X-rays were obtained at study entry and again at one and two years. Joint space width was measured on 581 knees from 357 patients. None of the trial groups showed significant improvement. The group taking glucosamine had the least change in joint space width, followed by the groups taking chondroitin sulfate, celecoxib, placebo and the combination of both dietary supplements.
The total joint space width loss over two years for each group was:

0. 0.013mm (glucosamine)
0. 0.107mm (chondroitin sulfate)
0. 0.111mm (celecoxib)
0. 0.166mm (placebo)
0. 0.194mm (glucosamine and chondroitin sulfate)

The interpretation of the results was problematic because the placebo group's joint space width loss was much less at two years than the 0.4mm the researchers' expected. Based on other large studies published in scientific journals, the researchers hypothesized that a loss of 0.2mm or less at two years would mean a slowed rate of cartilage loss. However, because the reduction in rate of joint space loss for all the groups was under the 0.2mm threshold, the researchers concluded none of the agents significantly slowed the loss of joint space width.
Josephine P. Briggs, M.D., director of the National Center for Complementary and Alternative Medicine, one of the study's funders, said although no definitive conclusions can be drawn about the two dietary supplements yet, "the results of the study provide important insights for future research."
Clegg said the trial shed light on osteoarthritis progression, techniques that can more reliably measure joint space width loss, possible effects of glucosamine and chondroitin sulfate, and on identifying patients who may respond best as further studies are pursued.

Thursday, January 29, 2009

Exercise Good For Bad Knees

Exercise Plays Large Role in Recovery from Knee Replacement and the Occurrence of Osteoarthritis
Two new studies found that exercise may be a factor in recovering from a total knee replacement (total knee arthroplasty or TKA) and knee osteoarthritis (OA). One study involving a progressive quadriceps strengthening program after total knee replacement found that it enhanced clinical improvement almost to the level of healthy older adults. The other study, the first to examine the relationship between four components of physical activity and the incidence of knee OA in older adults, found that certain types of activities were linked to an increased risk of the disease. The studies were published in the February issue of Arthritis Care & Research (

Nearly half a million total knee replacements are performed each year in the U.S. to treat severe knee OA, which is on the rise due to an increase in the elderly and overweight populations. Although knee replacement improves function, patients continue to have impaired quadriceps strength and function for activities such as walking and climbing stairs, which remain below those of healthy people of the same age. Rehabilitation targeting these areas has not been studied well and is not routinely prescribed.

A randomized controlled trial led by Lynn Snyder-Mackler of the University of Delaware and funded by the National Institutes of Health involved 200 patients who had undergone a knee replacement and 41 patients who received conventional standard of care (inpatient rehabilitation and home physical therapy). The 200 patients received six weeks of progressive strength training two or three times a week that targeted knee extension, range of motion, kneecap mobility, quadriceps strength, pain control and gait. Half of this group also received neuromuscular electrical stimulation (NMES).

The results showed that those who did the strength training program had significant improvements in quadriceps strength and muscle activation, functional performance and self-reported function and that they also demonstrated substantially greater quadriceps strength and functional performance after 12 months than the standard of care group. There were no significant differences between the group that just did exercise and the group that did exercise plus NMES.

“Our data suggest that individuals who do not undertake an intensive rehabilitation program following TKA are clearly at a disadvantage,” the authors state. They point out that quadriceps strength is related to functional performance and was the single greatest predictor of function for activities such as rising from a chair or climbing stairs. Functional performance typically peaks about three years following surgery and slowly declines in the following 10 years. “Failing to obtain adequate functional recovery may accelerate functional decline and predispose these individuals to an early loss of functional independence as they age,” the authors conclude.

Another study published in the same issue and led by Led by Marjolein Visser of VU University Medical Center in Amsterdam involved almost 1,700 men and women ages 55 to 85 years old of the LASA study that were assessed over a 12-year period for knee OA. Their physical activity was evaluated with a questionnaire that included information on frequency and duration of physical activity over a two-week period. Intensity, mechanical strain, turning action and muscle strength scores were created for each activity.

During the follow-up period, 28 percent of participants developed knee OA. Activities with low muscle strength (such as light household work) or high mechanical strain (such as dancing or tennis) were associated with an increased risk of knee OA, even after adjusting for demographics, health, and early life/current physical activity, as well as the other components of physical activity.

The study did not find an association between the level of overweight and mechanical strain in the incidence of knee OA. “This finding could indicate that the higher risk of knee OA in obese persons may be explained by factors other than increased mechanical strain, and higher levels of physical activity may not negatively affect knee health in heavier respondents,” the authors state.

The authors caution that before these results can be translated into advice for health professionals on daily activities for older adults, further studies need to be conducted to clarify the optimal amount of daily activity necessary for healthy joints for each component of physical activity.

Articles: “Improved Functioning From Progressive Strengthening Interventions After Total Knee Arthroplasty: A Randomized Clinical Trial With an Imbedded Prospective Cohort,” Stephanie C. Petterson, Ryan L. Mizner, Jennifer E. Stevens, Leo Raisis, Alex Bodenstar, William Newcomb, Lynn Snyder-Mackler, Arthritis & Rheumatism (Arthritis Care & Research), February 2009.

“Physical Activity and Incident Clinical Knee Osteoarthritis in Older Adults,” Lisanne M. Verweij, Natasja M. Van Schoor, Dorly J.H. Deeg, Joost Dekker, Marjolein Visser, Arthritis & Rheumatism (Arthritis Care & Research), February 2009.

No Joint Benefit From Glucosamine Or Chondroitin

September 29, 2008
No Joint Benefit From Glucosamine Or Chondroitin
If glucosamine and chondroitin provide any relief from osteoarthritis 572 study participants weren't enough to prove it.

The dietary supplements glucosamine and chondroitin sulfate, together or alone, appeared to fare no better than placebo in slowing loss of cartilage in osteoarthritis of the knee, researchers from the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) team report in the October issue of Arthritis & Rheumatism.[1] Interpreting the study results is complicated, however, because participants taking placebo had a smaller loss of cartilage, or joint space width, than predicted. Loss of cartilage, the slippery material that cushions the joints, is a hallmark of osteoarthritis and its loss is typically measured as a reduction in joint space width—the distance between the ends of bones in a joint as seen on an X-ray.

Rather than slowing down the decay we really need ways to stop and reverse it. Some sort of stem cell therapy is the best bet. Gene therapy might end up helping but I expect benefits from stem cells sooner. Further out nanobots will do joint repair. I hope at least one of these becomes available before any of my joints start to ache.

Glucosamine might provide a small benefit. But if glucosamine does provide a benefit it is not so large that it shouts out.

Rheumatologist Allen D. Sawitzke, M.D., associate professor of internal medicine at the University of Utah School of Medicine, was lead investigator. "At two years, no treatment achieved what was predefined to be a clinically important reduction in joint space width loss," Sawitzke said. "While we found a trend toward improvement among those with moderate osteoarthritis of the knee in those taking glucosamine, we were not able to draw any definitive conclusions."

A whole lot of people suffer pain from osteoarthritis. How many do you know that live with constant osteoarthritic pain?


Chondroitin is a molecule that occurs naturally in the body. It is a major component of cartilage -- the tough, connective tissue that cushions the joints. Chondroitin helps to keep cartilage healthy by absorbing fluid (particularly water) into the connective tissue. It may also block enzymes that break down cartilage, and it provides the building blocks for the body to produce new cartilage.

A number of scientific studies suggest that chondroitin may be an effective treatment for osteoarthritis (OA). OA is a type of arthritis characterized by the breakdown and eventual loss of cartilage, either due to injury or to normal wear and tear, and commonly occurs as people age. Chondroitin supplements have been shown to decrease the pain of OA. Some researchers think it may actually slow progression of the disease, unlike other current medical treatments for OA. (Many people take either acetaminophen or nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen, for OA pain). However, so far studies have not shown conclusively that chondroitin helps repair or grow new cartilage, or stops cartilage from being further damaged. Chondroitin is often taken with glucosamine, another supplement thought to be effective in treating OA.

Therapeutic Uses



Results from several well-designed scientific studies indicate that chondroitin supplements may be an effective treatment for OA, particularly OA of the knee or hip. In general, findings from these studies suggest that chondroitin:

Reduces OA pain
Improves functional status of people with hip or knee OA
Reduces joint swelling and stiffness
Provides relief from OA symptoms for up to 3 months after treatment is stopped
However, the largest clinical trial so far, the 2006 Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), sponsored by the National Institutes of Health, showed conflicting and somewhat confusing results. The study of about 1,600 people with OA of the knee found that glucosamine and chondroitin did not reduce pain in the overall group, although it did appear to lessen pain among those with moderate-to-severe OA of the knee. The study has raised questions for further research. Since glucosamine and chondroitin were combined in this study, it is not possible to determine the effect of chondroitin alone. In addition, researchers are now studying whether the glucosamine-chondroitin combination may in fact help those with more severe OA.

Most studies have shown that chondroitin needs to be taken for 2 - 4 months before it shows effectiveness, although some improvement may be experienced sooner. Glucosamine and chondroitin can be used along with NSAIDs to treat OA.


Other conditions for which chondroitin has been suggested include preterm labor, Alzheimer's disease, heart disease, and osteoporosis. However, no studies have yet evaluated these claims.

Dietary Sources

There are no significant dietary sources of chondroitin, so people who want to take it must take supplements.

Dosage and Administration

Chondroitin is commonly sold as chondroitin sulfate in capsule or tablet form. It is often combined with glucosamine and sometimes manganese as well. Manganese is a trace element necessary for normal bone health. While the total amount of manganese from foods and supplements should not exceed 11 mg per day, several combination supplements for arthritis (containing glucosamine, chondroitin, and manganese) contain more than that. Read labels carefully, and consider choosing a supplement without manganese.

Chondroitin Slows Progression of Knee Osteoarthritis

Osteoarthritis (OA) causes disability and is a major public health problem. A new study examined the effect of chondroitins 4 and 6 sulfate (CS) on OA progression and symptoms. CS, unlike other chondroitin sulfate products sold as dietary supplements in the U.S., has been approved as a prescription symptomatic slow acting drug for OA in many European countries. The study was published in the February issue of Arthritis & Rheumatism (

Led by Andre Kahan of the University of Paris Descartes in Paris, the randomized, double-blind, placebo-controlled study involved 622 patients with OA from France, Belgium, Switzerland, Austria and the U.S. Patients had knee X-rays at the time of enrollment and at 12, 18 and 24 months. The X-rays were evaluated for joint space loss and patients were also assessed for OA symptoms and pain.

The results showed that "long-term administration of CS over 2 years can prevent joint structure degradation in patients with knee OA," the authors state. Joint space loss was significantly reduced in the CS group, fewer patients had progression of joint space width, and CS reduced pain in those taking it compared to the placebo group. CS was well-tolerated and there were no significant differences in the frequency of adverse events between the two groups.

The study showed that there was faster improvement regarding pain during the first year in the CS group compared to the placebo group. This may be due to the fact that all of the patients had pain symptoms, so the effect of CS was more noticeable early on. Since those who took a placebo also had decreased pain in the first year, it may also be due to the natural course of the disease. The authors note that the study involved CS, which is used as a prescription drug and that the results cannot be generalized to other chondroitin sulfate products or compounds, such as those available in the form of dietary supplements.

The decrease in joint space loss shown in this and another recent study involving 300 patients, suggests better outcomes for OA patients, according to the authors. They conclude: "Further studies with longer followup and different outcome criteria are warranted to assess whether the beneficial structural changes associated with CS demonstrated in our study are predictive of improvement in the long-term clinical progression of OA."

Article: " Long-Term Effects of Chondroitins 4 and 6 Sulfate on Knee Osteoarthritis," Andre Kahan, Daniel Uebelhart, Florent De Vathaire, Pierre Delmas, Jean-Yves Reginster, Arthritis & Rheumatism, February 2009.

Tuesday, January 13, 2009

Greater Quadriceps Strength May Help Bad Knees

Studies on the influence of quadriceps strength on knee osteoarthritis (OA), one of the leading causes of disability among the elderly, have shown conflicting results. In some studies, decreased quadriceps strength is associated with greater knee pain and impaired function, while other studies show mixed results on the effect of quadriceps strength on the structural progression of knee OA.

Most studies to date have used X-rays to indirectly measure cartilage loss in knee OA and have focused on the tibiofemoral joint (the main joint in the knee where the thigh and shin bones meet). A new study has examined the effect of quadriceps strength on cartilage loss (measured using magnetic resonance imaging [MRI]) at both the tibiofemoral joint and the patellofemoral joint (where the thigh bone and knee cap meet) as well as on knee OA symptoms. The study was published in the January issue of Arthritis & Rheumatism (

Led by Shreyasee Amin, M.D., M.P.H., of the Mayo Clinic, the study involved 265 men and women participating in a 30-month study of symptomatic knee OA. At the beginning of the study, participants underwent MRI of their more painful knee and measurement of quadriceps strength for the same knee. They were also asked to rate the severity of their knee pain and their physical function was assessed. The knee MRI and assessments of their knee OA symptoms were repeated at 15 and 30 months. A measurement of knee alignment was also performed.

The results showed that greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint even in those with knees that were out of alignment. However, stronger quadriceps were shown to protect against cartilage loss in the lateral compartment (outer part) of the patellofemoral joint, a site of frequent cartilage loss, pain and disability in patients with knee OA. The study also showed that those with the greatest quadriceps strength had less knee pain and better physical function than those with the least strength.

Previous studies had also shown no overall protective effect of greater quadriceps strength on cartilage loss at the tibiofemoral joint. The protective effect against cartilage loss at the lateral compartment of the patellofemoral joint is a new finding that needs to be confirmed in future studies, but does provide evidence as to the benefit of having strong quadriceps muscles in patients with knee OA. “Our findings, which also include an association of greater quadriceps strength with less knee pain and physical limitation over followup, suggest that greater quadriceps strength has an overall beneficial effect on symptomatic knee OA,” the authors state. This effect may be due to a strengthening of the vastus medialis obliquus (a quadriceps muscle that pulls the kneecap inward), that may stabilize the kneecap and help prevent cartilage loss behind part of the knee cap.

Although the study did not involve exercise training to strengthen the quadriceps, there have been several short-term studies that show that improving quadriceps strength has a beneficial effect on knee pain and function. “While our findings suggest that maintaining strong quadriceps is of benefit to those with knee OA, further work is needed to determine the type and frequency of exercise regimen that will be both safe and effective,” the authors conclude.

Article: “Quadriceps Strength and the Risk for Cartilage Loss and Symptom Progression in Knee Osteoarthritis,” Shreyasee Amin, Kristin Baker, Jingbo Niu, Margaret Clancy, Joyce Goggins, Ali Guermazi, Mikayel Grigoryan, David J. Hunter, David T. Felson, Arthritis & Rheumatism, January 2009; 60:1; pp.189-198.