Breakthrough bone study wins international acclaim | Action Medical Research

Touching Lives - June 2006

Breakthrough bone study wins international acclaim

A grant of £38,899 from Action Medical Research has put the ‘spondyloarthropathies’ on the medical map. International attention has been focused on the work into this little known group of rheumatic disorders, which includes ankylosing spondylitis and psoriatic arthritis; diseases which affect thousands of people in the UK and, in severe cases, can lead to parts of the backbone fusing into a solid rod.

Professors Mike Benjamin, based at Cardiff University, and Dennis McGonagle, from the Academic Unit of Musculoskeletal Diseases, University of Leeds, led the study which began in 2002. So far, no fewer than five influential papers have been published outlining the team’s work, with more in the pipeline. The research has attracted interest from the US, Germany, Italy and Japan.

The project focused on why spondyloarthropathies attack the sites in the body where tendons and ligaments attach to the skeleton.The disease causes stiffness and pain, and can lead to bones literally fusing together, severely impairing movement.

But diagnosis is not straightforward, and doctors had been puzzled as to why some patients feel pain at sites some distance from these ‘insertion’ points, where soft tissue is attached to hard bone. This research has given important new insights into why disease starts and progresses and could ultimately lead to more reliable and earlier diagnosis.

Overshadowed

Professor Benjamin says, ^”One of the problems with this condition is its name! It is such a mouthful and not one that is easily remembered.^ In recent years it has been overshadowed by research into rheumatoid arthritis, which everyone has heard of, even though conditions such as ankylosing spondylitis are relatively common.

“That lack of knowledge means that some patients with ankylosing spondylitis can wait years for an accurate diagnosis because the condition is often mistaken for something else. It can have a devastating effect on their lives and means that they may not get the treatment they need.”

The research team looked at the tiny areas of soft tissue trauma at or near insertion sites, particularly those subject to a high mechanical load, such as the foot. They carefully studied the sites where the tendons and ligaments attach and showed that there is much more to an insertion than meets the eye. Rather than simply a localised point, the neighbouring tissues can also be affected, giving us clues as to why sufferers may get symptoms over a wider area.

The pain caused by ankylosing spondylitis can be excruciating and the impact on the quality of life enormous. It affects more men than women. Children and adults can develop the condition, which has a strong genetic link and often runs in families.

Inflammation

Professor Benjamin says, “We were working on the notion that mechanical loading is important and that the inflammation which characterises the condition is triggered by stress at a particular site. ^We looked for areas of microdamage under the microscope and found evidence at the area where tendon or ligament joins bone.^

“It is not surprising really - ask a mechanical engineer about how difficult it is to attach two completely different materials together, and he will say the point of failure it likely to be the attachment site.”

This project has been one of the most successful with which Professors Benjamin and McGonagle have been involved. The research has clarified a fundamental question of how tendons and ligaments attach to bone and shows that scientists and clinicians should think of attachment sites as features in common with the roots of a tree - i.e. potentially spreading anchorage over a wider site. “As a scientist the work has been hugely satisfying. Not until I started this project did I realise how common ankylosing spondylitis is and what its effect can be”, says Professor Benjamin.

Professor Benjamin studied hundreds of tissue sections in the laboratory and both he and Professor McGonagle were recently invited to a conference in Italy to discuss their work with rheumatologists from around the world. Professor Benjamin says, “The rheumatologists see this as a breakthrough because it helps them understand the symptoms, and the fact that pain is not restricted to the immediate site but may cover the adjacent area.”

The study is unique and late last year Professor Ignazio Olivieri, a leading Italian rheumatologist, said that the work of Professors McGonagle and Benjamin had been of central importance in stimulating a revival of interest in the whole field.

Professor McGonagle says, “The immune system triggers the inflammation which is present in ankylosing spondylitis and which causes pain, but our research has highlighted for the first time the role played by the site at which soft tissue is attached to the bone, and the impact that damage there can have. As a clinical scientist, I find our results so far very exciting and the study has attracted a lot of interest. Our tissue studies have helped us make sense of MRI scans in patients with early disease.

“These conditions are not uncommon and can be misdiagnosed in their early stages. Now we know why patients feel pain and have trauma across a wider area than simply the point of insertion into the bone, and that helps us understand the potential progression of the condition. Hopefully this better understanding will help eventually lead to a better treatment.”

Professor Benjamin says, “The benefits will come largely from the clearer understanding that clinicians will have about insertion sites, especially in educating them about viewing tendon or ligament insertions as ‘mini organs’, rather than simply as focal areas of attachment. It should help them to appreciate how a patient can have symptoms over a wider area.”

Fighting for a diagnosis

It took 14 years for Tim Gould to be diagnosed with ankylosing spondylitis. Tim, a laboratory manager in Life Sciences at the University of Cardiff, fell off his bike in 1983 and developed a painful lower back, which was originally diagnosed as sciatica.

He saw a succession of doctors and specialists as he gradually lost mobility in his lower spine, chest and neck and also developed problems with his eyes and feet. He had to endure nights sitting bolt upright in a chair unable to move and terrified of what was happening to him. ^One specialist told him to stop worrying, go home and have a few beers - a real low point for Tim, who knew by then there was something seriously wrong.^

He says, “I was in severe pain and in no fit state to do battle with doctors and specialists trying to prove that I had a real problem and that it wasn’t all in my mind.

“When I was finally diagnosed I wasn’t really surprised, as I had read up on it and seemed to have all the symptoms, but it demonstrates how important research is so that a faster and more accurate diagnosis can be made. My daughter has been diagnosed with ankylosing spondylitis too, and went through the same slow process as me.”

The condition means that Tim has to take drugs every day to control the pain. His sleep is badly affected because he has to wake up several times a night to move to a more comfortable position. Tim can no longer turn his head to either side as areas of inflammation have gradually fused the bones in his back together. He also has an eye condition called iritis, which flares up intermittently and requires hospital treatment to stop permanent damage being caused to his vision.

Tim has shared his experiences of living with the condition with Professor Benjamin, which proved a valuable contribution to the study into the spondyloarthropathies.

Tim, who lives in South Glamorgan, says, “The way my body looks makes me feel embarrassed, but socially I can join in with most things as long as my pain is under control. At times I have been quite depressed about the way my condition has affected my life.

^”The stress of having to take drugs constantly to stay relatively pain free is upsetting and worrying^ and they have affected me quite badly, causing severe heartburn, which can lead to stomach ulcers in some people. Luckily my job is not a manual one so I haven’t had too many problems with work, but I find it sad that I had to fight for so long to be diagnosed.

“Research is vital not only for faster and more accurate diagnosis, but also for more effective treatment for the patient.”

Thanks go to SEARCH for funding this project

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