Long-term randomized trial of intensive versus symptomatic management in Paget's disease of bone: The PRISM-EZ study

Adrian Tan, Kirsteen Goodman, Allan Walker, Jemma Hudson, Graeme S. MacLennan, Peter L. Selby, William D. Fraser, Stuart H. Ralston (Lead Author), PRISM-EZ Trial Group

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It has been suggested that normalization of bone turnover may improve clinical outcome in Paget’s disease of bone (PDB) by preventing complications such as fractures and the progression of osteoarthritis. Here we investigated the long-term effects of a treatment strategy that aimed to normalize bone turnover in PDB with that of symptomatic treatment. The study group comprised 502 subjects who were enrolled into a three-year extension of the Paget’s Disease: Randomised Trial of Intensive versus Symptomatic Management (PRISM) study. Intensive bisphosphonate therapy was continued in 270 of these subjects with the aim of normalising serum total alkaline phosphatase (ALP) concentrations using zoledronic acid as the treatment of first-choice. Symptomatic treatment was continued in 232 subjects where bisphosphonates were given only if there was bone pain thought to be caused by PDB. The primary outcome was fracture and secondary outcomes were orthopaedic procedures, quality of life and bone pain, adjusted for baseline characteristics. Serum total ALP concentrations were significantly lower in the intensive group on entry to the study and the differences between groups increased as the study progressed. There were no clinically important differences in quality of life measures or bone pain between the treatment groups. Intensive treatment was associated with a non-significant increase in fracture risk (hazard ratio =1.90, [95% confidence interval 0.91 to 3.98], p=0.087), orthopaedic procedures (1.81 [0.71 to 4.61], p=0.214), and serious adverse events (relative risk 1.28 [0.96-1.42].
We conclude that long-term intensive bisphosphonate therapy confers no clinical benefit over symptomatic therapy and is associated with a non-significant increase in the risk of fractures, orthopaedic events and serious adverse events. The results of this study suggest that in patients with established PDB, bisphosphonate therapy should focus on control of symptoms rather than suppression of bone turnover.
Original languageEnglish
Pages (from-to)1165–1173
Number of pages9
JournalJournal of Bone and Mineral Research
Issue number6
Early online date8 Feb 2017
Publication statusPublished - Jun 2017

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