Chondroitin sulfate improves hand function, relieves morning stiffness caused by osteoarthritis


New research shows that chondroitin sulfate significantly decreased pain and improved hand function in patients with osteoarthritis (OA) of the hand compared with those in the placebo group. Results of the clinical trial available today in Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR), also report that chondroitin sulfate improves grip strength and relieves morning stiffness.

The ACR estimates that OA—the most common form of arthritis—affects more than 27 million adults in the U.S., causing joint pain and stiffness. Approximately 10% of the world population, 60 years and older, have symptomatic osteoarthritis according to the Global Burden of Disease 2000 report from the World Health Organization (WHO). Prior studies have found that 20% to 30% of adults have OA of the hand, with the prevalence rising to more than 50% after 60 years of age.

"Although hand OA is highly prevalent among adults and can significantly impact the quality of life for suffers, therapeutic options are still limited," said Cem Gabay, M.D., with University Hospitals of Geneva in Switzerland and lead investigation of the Finger osteoArthritis Chondroitin Treatment Study (FACTS). "There are few trials examining therapeutic approaches specific to hand OA and much of the available evidence has been extrapolated from studies investigating other forms of OA."

The single-center, placebo-controlled FACTS trial included 162 patients with radiographic hand OA who met inclusion criteria—spontaneous hand pain on the visual analogue scale (VAS) of 40 mm (scale 0-100) or more and Functional Index for Hand OA (FIHOA) level of 6 (scale 0-30). Participants received either 800 mg of chondroitin sulfate (80 patients) or placebo (82 patients) once daily for 6 months.

Results showed that patients in the chondroitin sulfate group had significant decrease in global hand pain compared with the placebo group, reflecting an 8.7 decrease on the VAS. Hand function also improved significantly for those taking chondroitin sulfate, decreasing more than 2 points on the FIHOA. Researchers also reported significantly improved hand function and reduction in morning stiffness for participants taking chondroitin sulfate versus placebo.

"Our findings show chondroitin sulfate is a safe and effective treatment for patients with hand OA," concluded Dr. Gabay. "Alternative therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), provide similar pain reducing effects, but with considerably more long-term toxicities." Chondroitin sulfate is a naturally occurring molecule and a main component of joint cartilage. The chondroitin sulfate agent used in this study (Chondrosulf®) is licensed as a drug in Europe and not as a nutripharmaceutical; in the U.S. chondroitin sulfate is sold as a supplement and often paired with glucosamine.

More information: Symptomatic Effect of Chondroitin Sulfate 4&6 in Hand Osteoarthritis: The Finger osteoArthritis Chondroitin Treatment Study (FACTS): A Randomized Double-Blind Placebo Controlled Clinical Trial." Cem Gabay, Carole Medinger-Sadowski, Danielle Gascon, Frank Kolo, Axel Finckh. Arthritis & Rheumatism; Published Online: September 6, 2011. DOI:10.1002/art.30574

New 'bouncer' molecule halts rheumatoid arthritis


Researchers at Northwestern University Feinberg School of Medicine have discovered why the immune cells of people with rheumatoid arthritis become hyperactive and attack the joints and bones. The immune cells have lost their bouncer, the burly protein that keeps them in line the same way a bouncer in a nightclub controls rowdy patrons.

The Feinberg School team has identified this bouncer, a protein called P21, which prevents immune cells from launching into their destructive rampage through thecartilage and bone. When the scientists developed and injected an imitation of the protein into an animal model of rheumatoid arthritis, the disease process was halted.

"The bouncer molecule stopped the immune cells from going crazy," said lead author Harris Perlman, associate professor of rheumatology at Northwestern's Feinberg School. "Imagine destructive customers in a bar, and the bouncer says, 'You are going to behave!' That's P21. This discovery opens up a new avenue for future therapies, which are greatly needed for rheumatoid arthritis."

Previous research by the Feinberg team showed people with rheumatoid arthritiswere low in P21, but the protein's role was unknown. The new study, which will be published in the journal Arthritis & Rheumatism, reveals the protein's vital role in keeping the immune cells in check.

Currently, there is no effective, nontoxic way to stop the hyperactive immune cells, Perlman said.

To develop the new approach, Perlman and his team tested five different parts, called peptides, of P21. He slipped each peptide into a "ghostlike" molecule that he injected into mice with a rheumatoid arthritis-like disease. The molecule secretly infiltrated the immune cells. After the seven-day trial, one of the tested peptides had calmed the overactive immune cells without toxic effects. Next, Perlman plans a 30-day study with the same peptide to monitor efficacy and toxicity over a longer period of time.

Existing treatments for rheumatoid arthritis include low-level chemotherapy and steroids. These are not always effective, however, and they are frequently accompanied by side effects. A newer class of therapy, which is sometimes used in combination with chemotherapy and steroids, is biologic response modifiers. These are antibodies or other proteins that reduce the inflammation produced by the hyperactive immune cells. These biologics don't work for everyone, though, and can be associated with side effects including the risk of infection.

Provided by Northwestern University (news : web)

Biological agents for rheumatoid arthritis associated with increased skin cancer risk


Biological agents used to treat rheumatoid arthritis seem to be associated with an increased risk of skin cancer, indicates a systematic review of published research in the Annals of the Rheumatic Diseases.

Inflammatory arthritis has been linked to an increased risk of some cancers, such as lymphoma and lung cancer, but a lower risk of others, such as bowel and breast cancers. But it has been unclear to what extent tumour necrosis factor (TNF) inhibitors - drugs which act on the immune system - might affect risk.

TNF inhibitors include the monoclonal antibodies infliximab and adalimumab and the protein etanercept.

The researchers base their findings on 21 studies and eight conference abstracts, which met their strict inclusion criteria of reporting data on cancer associated with TNF inhibitors. In all, this provided information on more than 40,000 patients and almost 150,000 cumulative years of exposure to these drugs.

The studies were drawn from an extensive trawl of clinical research databases, and findings presented to the American College of Rheumatology, the European League against Rheumatism, and the British Society for Rheumatology between 1998 and 2010.

The pooled risk from seven studies for the development of any cancer showed that there was negligible or no increased risk, overall.

Two studies indicated that there was no evidence that patients taking TNF inhibitors over the long term were at increased risk of cancer either. And although patients who had had cancer before were more likely to be diagnosed with the disease again, this was not affected by the use of TNF inhibitors.

But four studies showed that patients treated with these drugs were 45% more likely to develop skin cancer other than melanoma, with two studies indicating that patients taking TNF inhibitors were 79% more likely to develop a melanoma than patients not taking these drugs.

"This systematic review and meta analysis provides reassurance to physicians and patients that the treatment of [rheumatoid arthritis] with TNF inhibitors does not increase the risk of malignancy, particularly lymphoma," write the authors. "However, it does appear to increase the risk of skin cancer, including melanoma," they add.

Provided by British Medical Journal (news : web)

Chronic pain gene identified


British researchers say they have identified the gene that controls chronic pain, opening the door to new drug therapies that block the chemical processes that cause chronic back pain, headaches or arthritis.

Chronic pain, defined as pain that is experienced most days of the week for at least three months, afflicts around 1 in 5 Australians. It commonly disrupts a sufferer’s ability to lead a normal life.

Now a team led by Professor Peter McNaughton, Head of the Department of Pharmacology at the University of Cambridge, has isolated a gene called HCN2 that produces a protein that causes chronic pain.

“Individuals suffering from neuropathic pain often have little or no respite because of the lack of effective medications. Our research lays the groundwork for the development of new drugs to treat chronic pain by blocking HCN2,” said Professor McNaughton.

His team conducted a series of experiments on mice genetically engineered to be born without the HCN2 gene. The researchers observed that these mice responded normally to normal acute pain (which is produced by a sudden injury) but that removing the HCN2 gene abolished neuropathic pain.

Being able to control chronic pain without affecting normal pain responses was crucial, he said.

“Many genes play a critical role in pain sensation, but in most cases interfering with them simply abolishes all pain, or even all sensation,” Professor McNaughton said.

“This finding could be very valuable clinically because normal pain sensation is essential for avoiding accidental damage.”

Professor Richard Lewis, an expert on chronic pain from the University of Queensland’s Institute for Molecular Bioscience, said the breakthrough was significant.

“This work appears particularly exciting as it, for the first time, directly links pacemaker channel HCN2 — a membrane protein important in controlling cell excitability — to the development of several difficult-to-treat painful conditions but not normal pain sensations,” said Professor Lewis, who was not involved in the research.

Chemical disruption of HCN2 could form the basis of much needed new pain therapies, he said.

“Building on previous research in this area, the work now highlights opportunities to discover and develop safer and more effective pain therapies that can selectively target HCN2 in pain pathways.”

The UK study was published in the September 9 edition of the journal Science. 

---

This story is published courtesy of the The Conversation (under Creative Commons-Attribution/No derivatives).

Exercise eases arthritis in obese mice even without weight loss


Adding another incentive to exercise, scientists at Duke University Medical Center have found that physical activity improves arthritis symptoms even among obese mice that continue to chow down on a high-fat diet.

The insight suggests that excess weight alone isn't what causes the aches and pains of osteoarthritis, despite the long-held notion that carrying extra pounds strains the joints and leads to the inflammatory condition.

Published Sept. 27 online in the journal Arthritis & Rheumatism, the findings are now being tested in people.

"What's surprising is that exercise, without substantial weight loss, can be beneficial to the joints," said Farshid Guilak, Ph.D., professor of orthopaedic surgery at Duke and senior author of the study. "Ideally, it would be best to be fit and lose a little weight, but this shows that exercise alone can improve the health of your joints."

Even modest improvements could have a major impact if the findings are borne out in people. The Arthritis Foundation reports that one in five adults in the United States have been diagnosed with arthritis, and the annual cost of treating it and other rheumatic conditions has been tabbed at $128 billion.

Many cases of arthritis are associated with obesity and inactivity, so the Duke researchers set out to determine whether a high fat diet induces knee osteoarthritis, and then whether exercise provides a protective effect.

Using two sets of male mice – half fed a high-fat diet and the other fed regular chow – the researchers noted significant differences among the two groups. The mice on the high-fat food gained weight rapidly, processed glucose poorly and had much higher blood levels of molecules that trigger the chronic inflammation associated with osteoarthritis.

But when these animals got regular running wheel workouts, many of the harmful effects diminished – even though the mice ate the same high-fat food and shed no weight. Glucose tolerance improved, while the inflammatory response was disrupted among key signaling molecules called cytokines, easing the development of arthritis.

If the extra weight on the joints had been the cause of the arthritis, the researchers noted, exercise would have exacerbated the problem. Instead, it helped.

"We're trying to understand the interaction of physical activity and obesity," said Timothy M. Griffin, Ph.D., lead author of the study. Griffin was formerly at Duke and is now at the Oklahoma Medical Research Foundation. "Even though there was the same amount of body fat, the fat was different."

Griffin said the fat cells still produced inflammatory molecules associated with arthritis, but they lost their punch because they could not organize into a force: "I don't want to say exercise is turning off that inflammatory signal, it just impairs it."

The findings add to a growing body of research exploring fitness vs. fatness. Ongoing studies at Duke and elsewhere are examining the role of diet, exercise and inflammatory diseases.

"This shows that if you are obese, it's better to exercise," Guilak said. "Sometimes pain can be a barrier to starting exercise, but if you overcome it, in the long term, it's better."

Provided by Duke University Medical Center (news : web)