Zipp Study Update

Paget’s Disease – a family affair
Zoledronate in the Prevention of Paget’s (ZiPP Study)

The Arthritis Research Council (ARC) and the Medical Research Council (MRC) are funding a new study.  The ZiPP 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. Many of you may well have rolled up your sleeves and given a blood sample.

Paget’s – the condition   Paget’s disease of bone is caused by abnormal bone turnover. This mainly occurs in people over the age of 50 and commonly affects the spine, hips and legs. Genetic factors play an important role in the disease and in many families, the condition can be passed down from one generation to the next.  Although some people with Paget’s disease don’t suffer ill effects, others can develop complications like pain, arthritis, deformity of the bones and deafness.
 
Paget’s disease can be treated with a group of drugs called bisphosphonates which slow down bone turnover (which is abnormal in Paget’s disease) and help to reduce bone pain.  Unfortunately, bisphosphonates do not appear to be effective in reversing complications of Paget’s disease when they have become established.  In view of this there is a need to determine if bisphosphonates might be able to prevent complications when given to people before they develop symptoms.

Paget’s - the research   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. Until recently there was no effective way of identifying those at risk of developing Paget’s disease until symptoms had appeared. 

However with breakthroughs in the identification of genetic mutations responsible for causing Paget’s disease it is possible to pinpoint people who may be at risk by a ‘genetic test’ which can be carried out on an ordinary blood sample. This is excellent news, as it means that if people who are likely to develop Paget’s disease could be identified at an early stage it might be possible to stop the disease ‘in its tracks’.

In Paget’s disease, bone turnover – the normal, 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), can  suppress these abnormalities of bone turnover for at least two years after a single short infusion.

Leading Paget’s disease expert, ARC Professor of Rheumatology at the University of Edinburgh and Paget’s Association Trustee, Stuart Ralston, has launched an exciting research project the ZiPP study to determine if Paget’s disease can be prevented in people who are genetically susceptible because of an abnormality in the ‘SQSTMI’ gene.  The study aims to find out whether Paget’s disease can be prevented in people who carry the genetic mutation by treating them with a single infusion of zoledronic acid.

The research team need to recruit about 600 people aged 30 years and above whose parents have Paget’s disease, and who are found, on testing, to carry the faulty gene. Recruitment will start in Edinburgh, Manchester, Liverpool, Sheffield and London with plans to open new centres in Nottingham and Oswestry in 2010.  The study will also involve researchers in Australia, Italy and Spain.

Half the patients will be given a single infusion of zoledronic acid; the other half will be given a dummy (placebo) infusion. Both groups will be followed annually, and their bone turnover checked for up to five years.