title: Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease.
abstract: BACKGROUND
  The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs.
  
  
  METHODS
  In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled.
  
  
  RESULTS
  At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P<0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P<0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers. The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months. Pain scores improved in both groups. During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P<0.001).
  
  
  CONCLUSIONS
  A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Paul
authors.initials: P
authors.lastname: Miller
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lyles
authors.forename: William
authors.initials: W
authors.lastname: Fraser
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.forename: Youssef
authors.initials: Y
authors.lastname: Saidi
authors.forename: Peter
authors.initials: P
authors.lastname: Mesenbrink
authors.forename: Guoqin
authors.initials: G
authors.lastname: Su
authors.forename: Judy
authors.initials: J
authors.lastname: Pak
authors.forename: Ken
authors.initials: K
authors.lastname: Zelenakas
authors.forename: Monica
authors.initials: M
authors.lastname: Luchi
authors.forename: Peter
authors.initials: P
authors.lastname: Richardson
authors.forename: David
authors.initials: D
authors.lastname: Hosking
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D010001:Osteitis Deformans / Q000097:blood / Q000188:drug therapy*; D011788:Quality of Life; D000068296:Risedronic Acid; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000068296:Risedronic Acid; D012968:Etidronic Acid