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Paget's disease - all in the family

Published on 01 October 2008
Source: Arthritis Today

Paget's patient Frederick Hazell with Dr Anne Langston and Professor Stuart Ralston who are leading Arthritis Research UK's research project in Edinburgh

A new Arthritis Research UK study aims to treat people with Paget’s disease of bone before they even develop any symptoms in order to stop the disease happening, or at least to slow down its development. Jane Tadman reports.

Paget’s - the research

Rather like osteoarthritis, people with Paget’s disease of bone can have the condition for years without knowing about it, only for painful symptoms to develop in their sixties and seventies.

For research purposes, this is excellent news, as it means that 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.

Until recently, this remained a theoretical rather than realistic possibility. However, 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. This is a rare example of a real attempt to use the results of genetic studies to introduce a possibility of disease prevention. (This may also become feasible in osteoarthritis if Arthritis Research UK’s major new genome screening project, arcOGEN, identifies a number of genes responsible for causing osteoarthritis.)

In Paget’s disease, bone turnover – the normal, healthy process by which bone is regularly renewed – increases by up to 40 times. The resulting new bone is abnormal in shape and structure, and weaker than usual. It is known that a new bisphosphonate drug called zoledronic acid (brand name Aclasta), controls this accelerated bone turnover and results in Paget’s going into remission for up to two years after a single injection.

As a result, leading Paget’s disease expert, Arthritis Research UK Professor of Rheumatology at the University of Edinburgh Stuart Ralston, has launched an exciting new £483,000 research project funded by Arthritis Research UK over five years, to find out whether people who carry the genetic mutation but have no Paget’s symptoms develop a progressive increase in bone turnover. And more importantly he and his team want to establish if this can be prevented by treating them with a single infusion of zoledronic acid.

“It is possible that treatment with bisphosphonate therapy in clinically normal individuals who carry SQSTM mutations around the second to fourth decade could prevent the development of increased turnover,” explains Professor Ralston. “This could delay or even prevent the development of clinical disease and complications.”

The study will recruit a total of 735 people between the ages of 25 and 40 whose parents have Paget’s disease, and who are found, on testing, to have the faulty gene. Recruitment will start in in Edinburgh, Manchester, Liverpool and Sheffield, and also be expanded to Canada and centres in Europe. Half the patients will be given a single five mg infusion of zoledronic acid; the other half will be given a placebo infusion. Both groups will be followed annually, and their bone turnover checked for up to four years.

Paget’s – the condition

Paget’s disease of bone is a common disorder caused by accelerated bone turnover, most likely to affect older people. Genetic factors are important, and the disease is inherited in 15 and 40 per cent of cases.

Although in roughly ninety per cent of cases people have no symptoms, in the remaining ten per cent the main problem is bone pain. Increased blood flow though the bone can also lead to the bone feeling hot to the touch.

Because the affected bone expands, it can become deformed or distorted. This is most common in the legs, which can become bowed, sometimes leading to fracture; or in the skull, where there is a high risk of deafness. If the optic nerve is put under pressure from increased bone growth, there can be a disturbance of vision.

According to Marilyn McCallum, chief executive of the National Association for the Relief of Paget’s Disease (NARPD), says it’s hard to know exactly how many people have the condition because it is not always diagnosed. Estimates vary from between 250,000 and 750,000 UK cases.

Patients are often not diagnosed

“There is a problem with awareness and this often results in patients not being diagnosed,” she says. “If an older person goes to their GP and says they have got pain in their leg they are likely to be told they have osteoarthritis. They are most likely to be diagnosed if they have a blood test for something else and the Paget’s shows up, or if they have a health MOT check. But knowing what condition you have got is important, as is knowing there is effective treatment.”

The development of bisphosphonate drugs for Paget’s in the past ten years or so has transformed treatment, adds Ms McCallum. Pamidronate, or zoledronic acid given by infusion, or 60-day high-dose courses of risedronate can slow down bone turnover and also help to reduce bone pain, with only minor side effects.

Paget's remains a low profile condition

Despite these major improvements, Paget’s remains a low-profile condition, not widely recognised by many GPs, and is unlikely to often trouble the national press’s health pages.

Marilyn McCallum reckons this is partly because it affects older people, who largely remain invisible to the national media, there is nothing that can be done to prevent it (at the moment) and there is no cure. “But there are some good news stories,” she says. “I know of one person who was in a wheelchair with Paget’s but after treatment they could walk three miles a day.”

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