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Previous Volume 353:898-908 September 1, 2005 Number 9 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Deftos, L.J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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.

Source Information

From the University of Auckland, Auckland, New Zealand (I.R.R.); the Colorado Center for Bone Research, Lakewood (P. Miller); Duke University Medical Center, Veterans Affairs Medical Center, Durham, N.C. (K.L.); Royal Liverpool University Hospital, Liverpool, United Kingdom (W.F.); Le Centre Hospitalier Universitaire de Québec, Sainte-Foy, Que., Canada (J.P.B.); Novartis Pharma, Basel, Switzerland (Y.S.); Novartis Pharmaceuticals, East Hanover, N.J. (P. Mesenbrink, G.S., J.P., K.Z., M.L., P.R.); and Nottingham City Hospital, Nottingham, United Kingdom (D.H.).

Address reprint requests to Dr. Reid at the Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand, or at i.reid{at}auckland.ac.nz.

Full Text of this Article

Related Letters:

Paget's Disease and Bisphosphonates
Liel Y., Rendina D., De Filippo G., Mossetti G., Reid I. R., Miller P., Hosking D.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:2616-2618, Dec 15, 2005. Correspondence

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