Multicentre randomised controlled trial of symptomatic versus intensive bisphosphonate therapy for Paget’s disease (PRISM trial)

Click here to open protocol as a pdf file.  The file will open in Acrobat Reader.


Paget’s Disease is the second most common metabolic bone disease in the UK affecting up to 3% of the population above the age of 55 years . Characterised by focal increases in bone turnover, Paget’s disease is a cause of substantial morbidity, causing diverse symptoms such as bone pain, pathological fracture, deafness, bone deformity, and secondary osteoarthritis.

The rationale for testing intensive versus symptomatic bisphosphonate therapy:

Bisphosphonates are regarded as the treatment of choice for Paget’s disease; short term studies have shown that they improve bone pain and inhibit biochemical markers of bone turnover in Paget’s disease, although the long term effects on disease progression are unknown. Recent studies have shown that new potent bisphosphonates like Alendronate and Risedronate are highly effective in suppressing accelerated bone turnover in Paget’s disease and for the first time, it has become possible to suppress biochemical markers of increased bone turnover to normal in a high proportion of cases . This has led to the suggestion that intensive therapy with these new potent bisphosphonates may be able to prevent long-term complications of the disease . The long-term effects of bisphosphonate therapy on complications of Paget's disease are unknown however, and there is no evidence that suppression of bone turnover with bisphosphonates improves long-term clinical outcome in Paget’s disease. Indeed, virtually all studies of bisphosphonates in Paget’s have been short term and have used biochemical markers of bone turnover as the primary endpoint. It is now important to conduct a long-term study to determine if these new potent bisphosphonates improve clinical outcome when compared with no treatment or symptomatic treatment with older, less effective therapies in Paget’s disease.

The questions which this protocol will address:

The trial described in this protocol will, therefore, examine whether intensive therapy with a potent bisphosphonate, sufficient to give long-term suppression of bone turnover, will be superior to symptomatic treatment in improving clinical outcome and preventing complications of Paget’s disease.

Click here to open protocol as a pdf file.  The file will open in Acrobat Reader.

Back to top

This page was last updated on 4th June 2004.