Focus on Edinburgh: research into practice
Published on 01 April 2011
Patients with bone and joint diseases are contributing to research which is leading to improved treatments, courtesy of a huge investment by Arthritis Research UK in Scotland’s capital city. Jane Tadman reports.
If there’s a successful model for how research and clinical practice dovetail together it’s in Edinburgh.
Patients with osteoporosis and Paget’s disease of bone, gout and osteoarthritis provide the samples of blood and DNA which are used in genetics and other studies and then directly benefit from the results of that research through better treatment and knowledge. It’s a virtuous circle.
Arthritis Research UK professor of rheumatology at the University of Edinburgh Stuart Ralston, who arrived in the city from Aberdeen six years ago, combines cutting-edge research into the genetics of bone diseases with treating patients. On the one hand he’s an internally renowned and much published expert in the field of bone disease research, and on the other he’s a medic running general rheumatology clinics at the Western General Hospital.
One of the first things he did on arrival in the Scottish capital was to set up an osteoporosis service for Lothian, which deals with 6,000 patients a year, and a fracture liaison service, where everyone over the age of 55 who has suffered a fracture gets the chance to have their bone density checked by a DEXA scan – and then offered the appropriate treatment.
“Setting up the service was important, and it also fits into our research,” explains Professor Ralston, who is based in the Institute of Genetics and Molecular Medicine and has grants totaling in excess of £2m from Arthritis Research UK.
99 per cent of patients agree to taking part in research
“We’re interested in the genetic basis of bone disease, gout and osteoarthritis and patients who come to the clinic are routinely asked if they’ll take part in research and give a blood sample, and 99 per cent of them say yes.”
As a result, the Edinburgh team has built up a biobank of more than 2,500 DNA samples, mostly from people with osteoporosis but also with Paget’s.
Paget’s disease of bone, which affects thousands of older people, leads to accelerated bone growth and consequent bone pain and often deformity in the skull, pelvis, spine and shin bones. It can be successfully treated by drugs also used to treat osteoporosis, called bisphosphonates.
There is a strong genetic element to Paget’s and the condition often runs in generations of families. One particular gene, called SQSTM1, has been identified and is known to play a part in its development: in fact, if anyone carries this particular genetic mutation there is a 90 per cent chance that they will develop Paget’s. However, carriers of the gene may not develop symptoms of the disease until they’re in their sixties and seventies.
Professor Ralston and his colleagues have now identified three more genes that predispose people to develop Paget’s disease, which they believe could lead to the development of a screening test to identify those most at risk. The results of their study, published in the leading journal Nature Genetics, confirmed that genes play a crucial role in the development of Paget’s disease, which explains why so many people have a family history of the condition.
And now in separate but linked research, the team are about to embark on a five-year experimental medicine grant from the charity that aims to find out if they can detect and treat Paget’s disease – many years before symptoms appear.
Stopping Paget’s disease before symptoms appear
They want to establish if the disease can be stopped in its tracks by treating patients with a single infusion of a bisphosphonate drug called zoledronic acid, which builds bone. Up to 800 patients will be involved from around the UK.
“Breakthroughs in identifying genetic mutations that are responsible for causing Paget’s disease have now made it possible for genetic testing to be carried out via a simple blood test,” says Professor Ralston.
“This is a rare example of a real attempt to use the results of genetic studies to introduce a possibility of disease prevention. If the people who are likely to develop Paget’s later in life can be identified in middle age, there is a chance to stop the disease in its tracks.”
The Edinburgh researchers are also working on the genetic basis of other rheumatic disease. In collaboration with Professor Alan Wright at the nearby MRC Human Genetics Unit they identified a gene that predisposes to gout. They also recruited more than 600 patients with osteoarthritis to the Arthritis Research UK funded arcOGEN study of osteoarthritis. Professor Ralston said: “We expect that the results of arcOGEN will be available soon and it’s likely that this will provide us with new insights into the genes that predispose to osteoarthritis. When that happens the next step will be to determine why these genes cause wear and tear of the joints. We’re well placed to conduct that research.”
The Edinburgh team is also extremely active in research into osteoporosis. Osteoporosis, or thin, porous bones, affects up to 30 per cent of women and 12 per cent of men at some point in life, and leads to around 200,000 fractures every year in the UK.
For the past three years researchers led by Dr Jim Wilson have been looking to identify the genes that predispose people to develop various diseases in the remote Isles of Orkney, one of which is osteoporosis. Up to 2,000 people have been recruited in Orkney, which was specifically selected because the population is isolated and stable, and specific genes are easier to track down and identify.
Research nurses have been running bone density scanning sessions in Kirkwall, and blood samples have been taken and screened for their DNA back in Edinburgh. Although the gene pool among Orkney families is isolated from the rest of the UK population, it’s expected that the results of the study, expected later this year, will be applicable to the wider population.
Stuart Ralston began looking at the effects of cannabis on bones when he was still in Aberdeen, and has published widely in this area. Recently he has found that the impact of cannabis on bone health varies dramatically with age. His most recent study has shown that although cannabis can reduce bone strength in young people, it may protect against osteoporosis in later life. After an investigation involving mice, the team showed that a molecule found naturally in the body which can be activated by cannabis – called a type 1 cannabinoid receptor – is key to the development of osteoporosis.
Testing the effect of cannabis on bones
The team is now planning to study the effects on cannabis on bone health in human volunteers; 200 heavy cannabis users from general practices in Edinburgh will be recruited to explore the possible adverse or other effects of recreational cannabis on their bones. Cannabis users’ diet, exercise and alcohol intake will also be taken into account, since these factors also influence bone health.
Of all the research achievements of the past five years, Stuart Ralston believes the genetic work on Paget’s that might lead to the condition being screened for and treated early has the greatest value. “To identify markers that identify people at risk for severe disease, and to be able to treat people with early disease to prevent complications happening, is very exciting. So much genetic research goes on that never has any practical application, or leads to anything, but this is different.”
He adds: “We have fabulous support from Arthritis Research UK, and without the charity’s support all this research would not have been possible. We’ve made huge advances in treating osteoporosis; finding the molecules that regulate bone turnover and turning them into drugs. The message is the power of biology, and Arthritis Research UK shouldn’t forget – and it doesn’t – about funding basic biology as well as clinical research.”