Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease.
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.
Reid
Ian R
IR
Department of Medicine, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz
Miller
Paul
P
Lyles
Kenneth
K
Fraser
William
W
Brown
Jacques P
JP
Saidi
Youssef
Y
Mesenbrink
Peter
P
Su
Guoqin
G
Pak
Judy
J
Zelenakas
Ken
K
Luchi
Monica
M
Richardson
Peter
P
Hosking
David
D
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
D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000068296:Risedronic Acid; D012968:Etidronic Acid