Rheumatologist says maintaining flexibility can prevent arthritis

The Pak Tribune reports findings from a study by Tim Spector, a professor of rheumatology at St. Thomas� Hospital in London, who claims his study shows that flexibility in women is associated with reduced risk of arthritis.

• It's not clear from the study if women were born with extra-flexible joints or obtained them through a lifetime of exercise and stretching, according to Tim Spector, a professor of rheumatology at St. Thomas' Hospital in London.
• "Our research suggests that both the innate or the exercise route (to flexibility) both seem to help prevent arthritis -- so exercise and stretching should be encouraged," said Spector.
• "In our study we only tested the women once and can't really separate hypermobile women who remained flexible from normal women who exercised and stretched to become more flexible than their sedentary peers," said Spector.
• It's the looseness of the structures surrounding the joint that allow it to have more motion, similar to a hinge on a door that allows it to swing open and closed.
• In some cases, hypermobility is a sign of inherited connective tissue or bone disease, and some studies had suggested it might actually increase the risk of osteoarthritis.
• Osteoarthritis occurs when the cartilage that cushions joints breaks down, often leading to pain, swelling and loss of mobility.
• In the ongoing study, predominantly middle-class white women have received regular x-rays and bone mineral density measurements since 1988.
• Spector and his colleagues found that bone mineral density was three percent higher in the hips of the hypermobile group compared with other women.
• There was no difference in spine bone mineral density between the two groups of women, according to the study in the current issue of the Journal of Rheumatology.
• The researchers also looked for osteoarthritis in the hands, knees, spine and hips of hypermobile women.
• The American Academy of Orthopedic Surgeons and the American Geriatrics Society recommend that adults engage in 30 minutes of moderate physical activity every day.

Dear Doctor: Causes, complications of neck arthritis

By Gerard Werries, M.D., Orthopedic Surgery

Q. Will I become paralyzed from my neck arthritis?

A. Arthritis of the neck is the leading cause of spinal cord dysfunction in patients 55 years and older. It affects men twice as much as women and can consist of bone spurs, disc bulges/herniations or thickened ligaments of the spine. Risk factors include frequent lifting, excessive driving and genetic and autoimmune factors.

Symptoms of neck arthritis can be neck pain, decreased motion, arm pain, numbness and weakness. Patients with significant spinal cord compression caused by severe neck arthritis often develop leg weakness, experience difficulty writing and walking and develop bowel and bladder difficulties.

If you have neck arthritis, you should have a thorough history taken and a physical done by a trained spinal surgeon. Routine X-rays of the neck should be done, after which additional imaging tests may be required to check the severity of spinal cord compression. Nerve conduction studies also may be required.

Patients with mild neck arthritis and minimal symptoms often respond well to physical therapy, anti-inflammatory medications and steroid injections. When conservative treatment fails or severe spinal cord compression from neck arthritis develops, surgery may be required to make room for the spinal cord and nerve roots. It is important for patients with severe spinal cord compression and significant neurological problems to seek immediate consultation with a spinal surgeon to avoid permanent damage to the spinal cord.

Osteoporosis drug fights knee arthritis

Risedronate preserves underlying bone to delay collapse of the joint

A drug that treats brittle bones may also help people with worn out knees.

British researchers have found that high doses of risedronate (brand name Actonel), an osteoporosis drug called a bisphosphonate, can preserve the underlying bone in the knee joints of people with osteoarthritis, the wear-and-tear form of arthritis.

"It has been known for some time within the literature that bisphosphonates could actually do this but nobody actually had the data to show it and so we are the first group to be able to do that," says Christopher Buckland-Wright, the senior study investigator and a professor of radiological anatomy at King's College London. He says the treatment slows the collapse of the joint and could potentially delay the need for knee replacement surgery.

Buckland-Wright and his colleagues studied 100 people who had knee osteoarthritis and were taking inactive pills or several different doses of risedronate. Over the next two years, X-rays showed that study participants with more advanced arthritis who were taking the higher medication doses experienced a halt or reversal in the loss of underlying bone in their knee joints.

People with advanced arthritis on the low-dose risedronate or inactive pills did not show any benefit, and those with less advanced arthritis had a modest loss of bone regardless of treatment.

Buckland-Wright says the drug was well tolerated even at high doses, and there is no reason to believe that other bisphosphonates would not also be effective.

Dr. Eric Matteson, professor of medicine at the Mayo Clinic in Rochester, Minn., says this study marks a new approach to slowing the progress of arthritis. "We now have a very good tool for slowing down this process, other than weight loss."

Arthritis patients denied drugs

By Nigel Hawkes

MANY patients with a form of arthritis that mainly affects young men are not being treated with drugs that could help them back into work. Ankylosing spondylitis (AS) affects about 60,000 people in Britain, and is most common among men in their late teens and early twenties. It impairs mobility and causes fatigue. The Arthritis Research Campaign (ARC) said that many patients were denied anti-TNF therapy, a new class of drugs that combat the inflammatory tumour necrosis factor, because of its high cost. Although it has been licensed for AS since 2003, the National Institute for Health and Clinical Excellence (NICE) is not expected to review its use in AS patients until February 2007. The ARC said that funding was patchy throughout the country and NHS trusts in England and Wales were not making the drugs available. It said that making the drugs more widely available would enable more patients to return to work. Professor Paul Wordsworth, of the ARC, said: “We urge NICE to speed up its approval process so that other people can benefit from the extraordinary transformation that these drugs can bring.”

New evidence to support combination therapy for achieving remission of early rheumatoid arthritis

Two-year study of patients with early, aggressive disease demonstrates significantly superior results of anti-TNF plus DMARD therapy over either therapy alone

A chronic and potentially crippling inflammatory disorder, rheumatoid arthritis (RA) progressively wears away the cartilage and bone. Joint erosions are routinely seen within 6 months of RA's onset, and occur more rapidly earlier in the course of the disease. Moderate disability within 2 years of diagnosis is not uncommon. While conventional DMARD (disease-modifying antirheumatic drug) therapies have been shown to slow joint destruction, they are powerless to stop RA's progression or reverse joint damage.

As researchers widely agree, early intervention offers RA patients the most promise for preventing irreversible joint damage and avoiding severe disability. In addition to early treatment, combination treatment, with DMARDs as well as with biologic agents, has been shown to yield more favorable outcomes than a single treatment. The January 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis) presents the first study to compare the effectiveness of DMARD therapy alone, anti-TNF (tumor necrosis factor) therapy alone, and a combination of DMARD and anti-TNF therapy. The compelling results affirm the long-term benefits of early combination therapy for women and men afflicted with aggressive RA.

The study was sponsored by Abbott Laboratories and conducted at 133 sites throughout North America, Europe, and Australia. It focused on patients with active RA for less than 3 years who had never been treated with the DMARD methotrexate (MTX). A total of 799 patients were enrolled in the study. The majority were women. The mean age was 52 years. 57 percent of the participants had RA for 6 months or less. The subjects were randomly divided into one of 3 treatment groups: MTX, in pill form, starting with 20 milligrams weekly; the anti-TNF adalimumab, administered by injection, starting with 40 milligrams every other week; and a combination of adalimumab plus MTX, starting at the same dosage levels as the single treatment groups. For all groups, treatment effectiveness was thoroughly evaluated after 6 months, 1 year, and 2 years. 539 of the participants completed 2 years of their assigned treatment.

In all outcome measured, the combination of treatments was clinically and statistically superior to both adalimumab and MTX alone. Following 1 year of treatment, 62 percent of patients in the combination therapy group had 50 percent improvement in disease symptoms, according to the standard American College of Rheumatology criteria, compared with 41 percent of patients in the adalimumab only group and 46 percent of patients in the MTX only group. In addition, there was significantly less radiographic disease progression at 6 months, 1 year, and 2 years among patients in the combination treatment group than among those in either single treatment group. What's more, after 2 years of treatment, nearly half the patients in the combination therapy group exhibited a major clinical remission, rates approximately twice those found among patients receiving either single therapy.

The combination of DMARD and anti-TFN therapy proved safe and well tolerated by patients. The incidence of infections and other adverse events were low and comparable in all 3 treatment groups. What's more, increasing the dosages of either adalimumab or MTX alone failed to yield the improvements experienced by patients receiving both treatments in relatively low dosages.

As spokesperson George T. Spencer-Green points out, the study's participants had an unusually high level of radiographic damage present at baseline for their average disease duration of under one year. Early RA patients with milder forms of the disease may benefit from early DMARD therapy under a clinician's supervision. "For the patient with early, aggressive and erosive, RA," he notes, "treatment with combination therapy is superior to treatment with MTX alone."

Canadian study focuses on pain management for arthritis sufferers

Mary-Ann Fitzcharles, M.D., of Montreal General Hospital, McGill University, led a study of pain management for arthritics that incorporates diet, exercise, topical applications and opioid analgesics in its treatment of the ailment.

• Long treated as a side effect, pain is now widely recognized as an integral part of patient care.
• While the last decade has brought extraordinary advances in the unravelling of pain mechanisms at the molecular level, evaluating and alleviating pain remains an ongoing challenge for physicians, particularly rheumatologists.
• The December 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis) offers a timely examination of pain as it pertains to rheumatology practice.
• "Pain management is no longer simply a quick fix with a single pill, but rather an approach to the patient as a whole biopsychosocial being."
• Drawing on the latest research into this complex factor, Dr. Fitzcharles and her collaborators demystify both the process and the experience of pain for patients with rheumatoid arthritis (RA) and related diseases.
• Because rheumatic pain travels through small, slow-conducting fibers, it is perceived as a pervasive aching rather than as acute, localized stabs.
• Inflammation also plays a role in activating pain pathways that usually lie dormant -- comprising as many as one-third of the total number of pain-transmitting nerves.
• What's more, molecular evidence suggests that stress and depression may increase a rheumatic patient's production of pain-provoking inflammatory agents.
• In addition to using time-honored tools -- namely, the visual analogue scale of pain severity and patient questionnaires -- in real-life practice, the rheumatologist must take cues from the patient during the interview and examination, heeding spontaneous movement, musculoskeletal structure, and verbal complaints, as well as consider the patient's psychosocial history and coping strategies.
• Beyond the prescription of a pill, what works to relieve rheumatic pain?
• According to studies, regular physical activity not only maintains muscle tone and helps to improve function, but also induces the production of endogenous opioids -- endorphins and other natural painkillers.

The impact of smoking and genes on rheumatoid arthritis

Researchers offer new insight into specific autoimmune triggers among smokers with shared epitope genes

Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases, and one of the least understood. Smoking is the major known environmental risk factor for RA, though little is known about the mechanisms involved. HLA-DR shared epitope (SE) genes are a widely recognized genetic risk factor for RA, though little is known about how these genes affect autoimmune reactions that lead to chronic inflammation and progressive joint and organ damage.

To better understand the interactions between smoking and HLA-DR SE genes in RA, a team of researchers in Sweden focused on the disease's distinctive autoimmune hallmark: citrulline, an amino acid not normally present in protein. While extremely rare in healthy individuals and relatively rare in other inflammatory conditions, citrulline-modified proteins are common in about two-thirds of RA patients and may be an underlying factor in the development of the disease. To investigate whether smoking and SE genes trigger immune reactions to citrullinated proteins, the team conducted a case-control study involving patients with recent-onset RA. The results, featured in the January 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), suggest that smokers with SE genes are more susceptible to anticitrulline antibody-positive RA.

The study's 930 early RA patients, drawn from the Epidemiological Investigation of Rheumatoid Arthritis Study Group, ranged in age from 18 to 70 years. 383 healthy controls, drawn from the blood bank of northern Sweden, were matched for age, gender, and residential area. All participants completed questionnaires about their past and present smoking habits, as well as genotyping profiles. In addition, bronchial fluid was obtained from a representative sample of RA patients, including both current heavy smokers and lifelong non-smokers, and tested with immunostaining for the presence of citrullinated protein in cells.

Based on their series of experiments and comparisons, the researchers found that a history of smoking increases the risk for RA, but only for individuals who test positive for anticitrulline antibodies, regardless of the presence of SE genes. Similarly, inheriting HLA-DR SE genes in a single copy, as well as in double copies, increases the risk for RA, but only for individuals who test positive for anticitrulline antibodies, including individuals who have never smoked. Yet, for individuals who test positive for anticitrulline antibodies, the interaction of smoking and carrying 2 copies of the SE gene dramatically increases the risk for developing RA--by 21 times.

"The remarkable gene-environment interaction observed in the case-control study, together with the immunostaining for citrullinated proteins, might now provide a clue to the molecular mechanisms of importance for disease development in a subset of RA patients," notes team spokesperson Dr. Lars Klareskog of Karolinska Institutet, Stockholm. "We may thereby be given some new opportunities to both predict and understand the onset of RA and to interfere with RA-inducing events before clinical symptoms are apparent."

Could knee stem cells offer new hope on arthritis?
Tom Perks has been an enthusiastic football player ever since he could kick a ball. But from about the age of 14, one of his knees would regularly give way during a game. It progressively grew worse and, eventually, got so bad he had to give up the game he loved. Now aged 23, Perks has just taken part in a trial for a radical new technique in which patients with injuries to the cartilage in their knee joints are injected with new cartilage grown from their own stem cells. At the moment, it is available only to relatively young, otherwise fit people, whose knee joints have been damaged, usually from a sports injury or accident. However, the technique offers new hope of preventing the pain and disability of arthritis in later life as a result of knee damage. Tom Perks is one of increasing numbers of people in Britain who have undergone autologous chondrocyte implantation (ACI). It requires two operations, one to remove cartilage cells (chondrocytes), which are then grown in the laboratory. Three or four weeks later they are re-implanted in the damaged area, where they are held in place by a patch either taken from the membrane covering the shin bone or by a manufactured collagen patch. Articular cartilage is a tough, smooth, elastic tissue which covers the ends of bones that form joints. It enables the bones to move smoothly over one another and performs the vital function of a shock absorber, cushioning the bone from forces of more than five times the body's weight. Damaged articular cartilage in knees can cause the joint to be painful, swollen and difficult to move, restricting once-swift athletes to a hobble. A line-up of foot-ballers' knees is testament to how much damage contact sports can do to the delicate engineering of the knee joint. Unlike skin, cartilage does not have the ability to repair itself. Instead, the damage tends to spread, allowing the bones to rub against each other. Any repair tissue that does form is not like the original cartilage and doesn't work very well. Royal Alexandra Hospital in Paisley is conducting a trial of ACI along with 14 other hospitals in the UK and two in Norway. It is the only one in Scotland so far. Dr Heather Smith, the trial manager, based at the orthopaedic hospital in Oswestry, Shropshire, has so far recruited 60 patients for the trial as opposed to more traditional treatments. "We hope to have 600 patients eventually and there will be a long-term follow-up," she says. "We plan to analyse the results after five years and 10 years. The procedure was pioneered in Sweden in the mid-1990s by Lars Petersen, who treated Ole Gunnar Solskjaer, the injured Manchester United player, and is being used in the US and in Germany, with promising results so far. It is not available in this country on the NHS except as part of a trial." ACI is a more expensive technique, requiring two surgical procedures rather than one and therefore an increased risk as well as a longer rehabilitation period than other techniques. Dr Smith's trial is therefore part of an evaluation which will decide whether it should be available to NHS patients. Like Tom Perks, patients must have a very specific form of cartilage damage to take part in the trial. "You need stable knees – sometimes the cartilage we are trying to repair may be so damaged there is almost nothing to get hold of." Perks has no doubt the operation has been a success: "I had the operation at the end of August and my leg is now quite a lot better," he says. "It is still a bit swollen but I have no discomfort when walking, although I'm not up to a run. I have been back at work for four weeks. I am on my feet all day, because I repair roads and footpaths. "They look inside your knee with a camera to see how bad it is, then they make a couple of incisions to take out the cartilage. After four weeks the cells are grown and you have the second operation. For that, I was in hospital for three days. "I was attached to a machine which automatically bends and straightens your knee to keep everything moving. Then I went on to crutches and now I am walking normally. You have to keep up with the physio – it takes about two months for the leg to become weight-bearing and the rehabilitation programme continues for 12 months." To be eligible to take part, patients must have had a standard treatment which failed. There are several alternatives to ACI. The traditional one is debridement, which involves sucking or washing away loose and damaged pieces of cartilage via keyhole surgery. Abrasion or drilling takes this a step further until bleeding points are seen. The theory is that the underlying bone produces primitive blood cells which are then reformed into cartilage cells which cover the damaged area. Microfracture is a modification of the drilling technique. Debridement is carried out to form a stable perpendicular edge of healthy cartilage. Then multiple holes are made in the defect. Blood from the defect is washed away until a clot forms. This "super clot" is believed to be the optimal environment for tissue to regenerate within the lesion. The questions with these techniques, says Dr Smith, are whether the right type of cells are released, whether there are enough of them and whether they stay in the right place, whereas ACI is possibly a more accurate way of achieving regeneration of the cartilage. The great hope for ACI is that it results in permanent improvement. Patients for whom other treatments have failed, have only the alternative of a knee replacement, but these do not last for more than 15 years, so are not a good option for younger people. So far, ACI patients have reported continued improvements for up to two years, suggesting the transplanted cells may continue to form new cartilage for that length of time. It gives great hope to Tom Perks. He has been told to avoid contact sports for a while, but he hopes he might soon be able to have a kickabout with his five-year-old son and get back to the game he adores. "It would be great to get back on the pitch with the lads," he says.