Preliminary results from the PRISM study: a multicentre randomised controlled trial of intensive vs. symptomatic management for Pagets disease of bone
SH Ralston1, AL Langston2, MK Campbell2, G MacLennan2, PL Selby3 & WD Fraser4
Bisphosphonates are the treatment of choice for Pagets disease of bone (PDB). However, long-term effects on complications are unknown. The PRISM trial was a randomised controlled trial comparing symptomatic management and intensive bisphosphonate therapy for PDB, and involved 1324 patients followed for a median of 32 months (range 1248). Patients allocated to symptomatic therapy (n=663) were untreated unless they had bone pain, at which point they received analgesics/NSAID and if non-responsive bisphosphonates. Patients allocated to intensive therapy (n=661) received repeat courses of aminobisphosphonates with the aim of normalising serum total ALP. At baseline, 71% of participants had previously received bisphosphonates, but 48% had elevated ALP levels. Treatment groups were matched at baseline for treatment history, ALP and other relevant variables. Principal results from an intention to treat analysis show that intensive bisphosphonate therapy was more effective at normalising ALP than symptomatic therapy (P<0.001), with 81% of patients receiving intensive therapy achieving normalised ALP levels at 2 years. However, there was no significant difference between the groups in terms of fracture (P=0.803), joint replacement (P=0.851), quality of life (SF36 Physical summary P=0.795; SF36 Mental Summary P=0.311), or pain (clinician assessed Pagetic bone pain P=0.12; SF36 Bodily pain P=0.905). Similar results were obtained when data were analysed according to compliance. Both analyses were by regression with correction for baseline variables. We conclude that in this population, there was no evidence of increased benefit from intensive bisphosphonate therapy in terms of fracture, requirement for joint replacement, pain or quality of life. This suggests that symptomatic therapy is equally effective as intensive treatment in patients with established PDB. Further analysis is in progress to evaluate effects of intensive therapy on other outcomes such as progression of deafness and bone deformity.