A new way of looking at osteoarthritis
Published on 01 July 2009
Acknowledged as one of the world’s leading experts in osteoarthritis, Professor David Felson is promising a radical new approach to research and treatment of the condition, in an exciting five-year programme of work funded by Arthritis Research UK. Jane Tadman reports.
Research into developing new treatments for osteoarthritis have so far failed to produce anything remotely effective or safe, as the recent vioxx drug scandal showed when a popular painkiller for osteoarthritis had to be withdrawn worldwide after a number of related deaths.
While basic science attempts to chip away at the many possible causes, hampered by the fact that essentially osteoarthritis is not just one disease but several - involving cartilage, bones, joints and inflammation - patients struggle to find satisfactory pain relief, often turning in desperation to unproven supplements when conventional medicines fail to work. And while there are now many drugs on the market that slow down disease progression in inflammatory forms of arthritis such as rheumatoid, and which may even lead to remission in the not too distant future, a similar drug for osteoarthritis is acknowledged to be years away.
So is a completely new approach to treatment needed? Step forward David Felson, Professor of Medicine and Public Health at Boston University, leading world authority on musculoskeletal diseases, particularly osteoarthritis, regularly published in leading journals, principal investigator of the Framingham Study, one of the biggest epidemiological studies in the world, and a practising clinician.
And now he’s heading up research in the form of a £1.4m special strategic award for arc looking at ways of developing new treatment approaches for osteoarthritis.
One of the last unconquered musculoskeletal diseases
Although the nuts and bolts of Professor Felson’s research is not due to start until the summer, he is already spending one week a month at Manchester University, where he holds an academic post, and which he plans to do for the next five years, overseeing a large multi-disciplinary research programme and three planned clinical trials.
“Osteoarthritis remains among the last unconquered musculoskeletal diseases and one of the few chronic diseases of ageing for which there is no effective strategy to prevent disease progression,” he says. “And in order to conquer it more successfully, it needs to be addressed in a multi-disciplinary fashion. I would never pretend to study it just by myself, just as a rheumatologist, I’d only study it if there were enough folks who have the interest and the expertise to compliment my own – radiologists, engineers and biomechanics, physiotherapists, people who know about bone and muscle. If you assemble all these people and pose the right questions and encourage them to interact and talk with each other, we can hopefully answer those questions.”
Moving away from cartilage
What marks out Professor Felson’s approach as unusual is that he is moving away from concentrating on cartilage repair as a central treatment target.
“My own predilection is that cartilage is maybe not so important in dealing with and treating osteoarthritis,” he says. “I don’t say that it’s not important in the creation of disease, but once it’s developed, other changes occur in the joint and these then drive the process, and cartilage takes a back seat. It’s a radical position, and not generally accepted at all. One of the reasons I came to England is that some of the ideas that underline that position really emerged here.”
David Felson has reached his position by watching, with increasing frustration, a number of treatments that have been tested and have failed. “For example doxycycline, (an antibiotic in the tetracycline family) which ought to work if cartilage was the problem, but doesn’t; a trial of risedronate (a bisphosphonate drug used to reduce bone loss in osteoporosis) and a large number of compounds developed by the pharmaceutical industry that appear to stop cartilage loss, but don’t work in clinical osteoarthritis. We know that there is no correlation between cartilage damage on x-rays and pain, because cartilage has no pain fibres. The research road is littered with cartilage studies, and it’s reached a dead end.”
What Professor Felson proposes to concentrate on instead are treatments that may both relieve the pain of osteoarthritis and alter the structures in the joint that are the sources of this pain, bone marrow lesions, and synovitis – inflammation of the synovium, the fluid that surrounds the joint to keep cartilage slippery.
Bone marrow lesions may be a cause of pain
The advent of magnetic resonance imaging (MRI) which can detect changes in the joint more accurately than ever before, has shown that these bone marrow lesions - areas of bone damage which show up on MRI as white blotches - are seen more frequently in people whose knee osteoarthritis is painful than those whose knee osteoarthritis is not painful. And the lesions get bigger when pain gets worse, suggesting that they are a cause of pain.
Professor Felson and his group were among the first researchers to suggest that despite osteoarthritis being known as a degenerative condition, mild inflammation also plays a part in the development of osteoarthritis (which is why anti-inflammatories and steroid injections can be effective). Synovitis is seen in at least 50 per cent of patients with painful knee osteoarthritis, and previous studies have shown that if synovitis decreases, so does pain. So targeting synovitis is another important strand of the forthcoming research.
The aim of the research programme is to evaluate treatments that may affect bone marrow lesions and synovitis to see if they alleviate pain, and hundreds of people with osteoarthritis of the knee from the Manchester area are to be recruited over the next three years to take part in related studies.
The other novel idea to be pursued is that all patients with osteoarthritis do not need the same treatment, but rather subgroups of patients with knee osteoarthritis can be identified who will respond to targeted treatment. There are three different subgroups to be studied. First are those with patellofemoral osteoarthritis (affecting the joint between the undersurface of the knee cap and the femur). Second, there are those with disease localised to the inside of the knee and lastly, the team will evaluate people whose osteoarthritis includes prominent fluid swelling in their knees.
Targeting people with particular types of knee osteoarthritis into specific sub-groups is an important feature of the research, although there is inevitably some cross-over. “I think another reason why there may be a failure in the development of treatments is that people have thought it is a single disease,” adds Professor Felson. “There are similar elements in many patients but for treatment purposes we need to think of osteoarthritis as a different group of illnesses that needed to be treated differently.”
A need for urgent progress
In his osteoarthritis clinic in Boston, Professor Felson takes a multi-disciplinary approach to treatment, offering specific physical therapy depending on patient’s particular problems. With ageing and obesity an even greater crisis on the other side of the Pond than in the UK, he is acutely aware of the need for urgent progress. “I understand why people take supplements like glucosamine, even though they probably don’t work. I don’t try and stop people from taking supplements because we need something that helps people and if they think it helps, then who am I to know better?”
At the age of 56 Professor Felson is finding that the subject that has occupied him professionally for more than 30 years is also starting to affect him personally. “I don’t have knee osteoarthritis but I probably have a mild case of it in my hips,” he says. “I don’t want to have an x-ray because I don’t want to know. I know too much!”