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Abstract
Background: Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment
and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase
treatment compliance and persistence.
Objective: The aim of this study was to compare the tolerability and efficacy of 3 once-monthly
risedronate dosing regimens with those of risedronate 5 mg/d.
Methods: This Phase II, 6-month, randomized, double-blind, active-controlled, dose-ranging
study was conducted at 13 clinical research centers and hospitals in Croatia, Poland,
Canada, and the United States between April 2004 and June 2005. Post-menopausal women
aged 50 to 85 years with a lumbar spine T-score <-2.0 were randomly assigned to 1
of 4 treatment groups: risedronate 100, 150, or 200 mg/mo or 5 mg/d (active control),
administered PO for 6 months. Evaluation of tolerability, the primary study objective,
was based on adverse-event (AE) profiles and clinical laboratory values. Efficacy
evaluation, a secondary objective, was a noninferiority comparison of the changes
from baseline in bone mineral density (BMD) and bone turnover markers (BTMs).
Results: Of 370 patients randomized (91, 88, 88, and 103 patients in the risedronate 100-,
150-, and 200-mg/mo and 5-mg/d groups, respectively), 57% were ≥65 years of age and
99% were white; 316 patients (85.4%) completed the study. Completion rates were not
significantly different across treatment groups, nor were reasons for discontinuation.
Between-group differences in the incidences of treatment-emergent AEs, serious AEs,
and upper gastrointestinal (GI) AEs were nonsignificant. Overall, 6 (7%), 14 (16%),
6 (7%), and 9 patients (9%) withdrew because of AEs in the 100-, 150-, and 200-mg/mo
and 5 mg/d groups, respectively. GI disorders were the AEs that most frequently led
to study withdrawal (5 [5.5%], 7 [8.0%], 4 [4.5%], and 6 [5.8%]). No trends were observed
in the nature or frequency of other AEs causing withdrawal. All serious AEs were considered
unrelated to treatment, with the exception of erosive esophagitis in 1 patient (1%)
who received the 5-mg/d dose. Mean percentage increases in BMD were 2.10%, 2.99%,
and 3.38% with risedronate 100, 150, and 200 mg/mo, respectively, versus 3.05% with
5 mg/d. At the 2 higher monthly doses, the changes from baseline in BMD were not significantly
different from those in the 5-mg/d group. Mean BTM values were decreased significantly
from baseline in all 4 treatment groups, and the changes from baseline at 6 months
at the 2 higher monthly doses were not significantly different from those at 5 mg/d.
Conclusions: Overall, in this study, the safety profiles of risedronate 100, 150, and 200 mg/mo
were not different from that of risedronate 5 mg/d. Changes in efficacy measures in
the monthly treatment groups were considered dose related and were not significantly
different between the 5-mg/d group and the 150- and 200-mg/mo groups; similarity was
greatest with 150 mg/mo.
Key words:
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Article info
Publication history
Accepted:
November 21,
2008
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.
