Researchers study whether people’s genetic makeup could make them more likely to develop osteoarthritis of the knee and hip

Aug 3 2004

Researchers at The University of Nottingham are studying whether people’s genetic makeup could make them more likely to develop osteoarthritis of the knee and hip — the most common medical condition to affect the joints.

The experts in the University’s Division of Academic Rheumatology have been awarded £371,000 in funding from the pharmaceuticals giant GlaxoSmithKline to look at the Genetics of Generalised Osteoarthritis, which they hope could one day help doctors to identify patients most at risk of developing the condition in later in life.

Osteoarthritis, or OA as it is commonly referred to, is a condition that has affected humans for thousands of years, known through the study of skeletal remains left behind by our ancestors. It is characterized by the localised breakdown of cartilage, a layer of tissue that cushions the ends of the bones and allows the joint to work smoothly. This loss of cartilage is accompanied by extra bone growth around the edge of the bones. The combination of cartilage loss and bone remodelling may lead to restriction of joint movement and eventual deformation of the joint. It is thought to be caused by a malfunction of the natural, in-built process that repairs the body’s joints following trauma or damage.

The largest cause of disability among the retired, OA represents a huge burden on the NHS and benefits system, which is only set to increase due to the ageing population. Patients who suffer from OA experience pain when bearing weight on the affected joint and find it difficult to carry out everyday tasks like climbing stairs or stepping in and out of the bath.

The Nottingham research is looking at the genetics behind OA. Siblings of people affected by OA of the knee are at double the risk of developing the condition themselves, while those who have a brother or sister with OA of the hip have a three or four-fold chance.

In an earlier study Nottingham, along with The University of Sheffield and four centres in the USA, recruited 1,200 families affected by OA of the hands. X-rays of the hip and knee were taken from siblings, as well as blood samples and measurements of bone density. The patients were also given a detailed questionnaire about their lifestyle and physical activity to fill in.

The genes of half of the families were then carefully studied to identify those that may have subtle variations that could make the patient more susceptible. The researchers are now studying the remaining 600 families to test whether the genes they believe are responsible are also present in those patients.

Now in its second round, the study is catching up with patients who took part in initial research to carry out more tests and x-rays to find out whether and how quickly their OA has progressed. This may indicate whether the genes also control the speed at which the condition develops.

If doctors could identify people at risk of developing OA they could offer advice on diet and lifestyle that could improve the outlook for their patient. Weight loss and exercise can make a huge difference — it is estimated that, if obesity was reduced by 20 per cent and people took a reasonable amount of aerobic exercise and reduced their chances of injury through their occupation, the number of OA hip and knee cases would fall by one-quarter.

A further four-year study at Nottingham, funded with around £1 million from AstraZeneca, is carrying a detailed questionnaire of 1,000 knee OA patients, 1,000 hip OA patients and a sample of 1,000 of the normal population to assess how lifestyle factors could interact with their genes to cause the condition.