The optimal management strategy for Pagets disease of bone (PDB) remains to be established although recent clinical guidelines have suggested that bisphosphonates should be given to maintain alkaline phosphatase (ALP) concentrations within the mid reference range. We report upon the long term outcome of treatment in PDB within the PRISM-extension with Zoledronic acid study (PRISM-EZ) in which 502 PDB patients, who all participated in the PRISM study, were followed for an additional 3 years. There were two treatment groups; symptomatic therapy (n=232) where bisphosphonates were only given if symptoms were present and intensive therapy (n=270) where bisphosphonates were given with the aim of maintaining ALP within the reference range. Zoledronic acid was the bisphosphonate of choice in the intensive group. Mean concentrations of ALP were in the mid-reference range in the intensive group throughout the study (mean±S.D. normalised ALP=0.71±0.30) but at the upper end of the reference range in the symptomatic group (1.01±0.81; P<0.001 between groups). There was no significant difference between treatment groups in bone pain and quality of life scores assessed by the SF36 questionnaire. Thirty-eight patients suffered a fracture (23 in the intensive and 15 in the symptomatic treatment groups, respectively). Six out of the above 38 patients had fracture of bone affected by PDB. Sixteen patients required orthopaedic surgery. Patients randomised to receive intensive bisphosphonate therapy were more likely to experience a fracture or undergo orthopaedic surgery than those in the symptomatic arm (Hazard ratio 1.94, 95% CI 1.073.51, P=0.029) and this remained significant after correction for baseline characteristics (HR 1.85, 95% CI 1.023.38, P=0.044]. We conclude that intensive bisphosphonate therapy confers no benefit in patients with PDB and on the contrary may be harmful. Treatment should be directed at patient symptoms rather than keeping ALP concentrations within the reference range.
Disclosure: S Ralston acts as a consultant for Novartis and Merck on behalf of his institution, the University of Edinburgh. W Fraser acts as a consultant for Procter & Gamble, MSD, Novartis, Sanofi Aventis, Nycomed and Roche. The remaining authors have no interests to declare. The PRISM-EZ study was supported by a grant from Arthritis Research UK.