A McMaster University endoscopy study found in the September issue of Gastroenterology and presented at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) showed that risedronate sodium (Actonel(R)) reduced the incidence of gastric ulcers in healthy, postmenopausal women relative to another osteoporosis
therapy, alendronate sodium. Research demonstrated that gastric ulcers
developed in three times as many participants treated with alendronate as
those treated with risedronate.
In another separate study presented at ASBMR, risedronate was as well-tolerated as placebo in women who had previously discontinued alendronate therapy due to upper gastrointestinal (GI) adverse events. The study published in the Journal of Managed Care Pharmacy found that discontinuation of alendronate therapy within the first six months of treatment occurred in 35 percent of patients,
most often because of gastrointestinal complaints (51.9 percent).
"An osteoporosis medication -- long-term or otherwise -- can work only if
a patient can tolerate the medication. It will be exciting to see how the
results of endoscopy studies translate to differences in event rates and
tolerability in clinical practice," said Dr. John Marshall, Assistant
Professor, Division of Gastroenterology, McMaster University, Hamilton,
About the Endoscopy Study
In the study presented by Dr. Marshall, gastric ulcers occurred in
69 percent fewer study participants treated with risedronate compared to those
treated with alendronate (4.1 percent vs. 13.2 percent, respectively;
(p <0.001). The two-week, clinical study enrolled 515 healthy, postmenopausal
women who received 5 mg of risedronate or 10 mg of alendronate for the
duration of the study. These women were required to abstain from medications,
such as nonsteroidal anti-inflammatory drugs (NSAIDs), and activities, such as
smoking, that have the potential to irritate the GI mucosa.
Gastric ulcer incidence is a recognized outcome measure in comparative
endoscopy studies evaluating medications known to irritate the gastric mucosa.
Gastric ulcers are important because they can be associated with clinically
relevant complications such as gastric bleeding or perforations. The other
key study criteria, including use of endoscopic evaluation rather than
symptomatology and study duration, also have been commonly used in studies of
cyclooxygenase-2 (COX-2) and NSAIDs.
Tolerability is a critical attribute when considering an osteoporosis
medication. In fact, a favorable drug safety profile was cited as the most
important characteristic of an osteoporosis medication by 93 percent of
physicians surveyed recently at the World Congress on Osteoporosis.
"Endoscopy studies are one important measure of tolerability and safety. The
combination of efficacy, tolerability and other safety parameters provides us
with the best means of evaluating these agents," Dr. Marshall said.
Currently, there are no head-to-head data comparing the efficacy, overall
safety, and tolerability of risedronate and alendronate in the treatment of
postmenopausal or glucocorticoid-induced osteoporosis. Long-term studies
comparing the incidence of serious, clinically-significant upper GI adverse
events in patients taking risedronate versus alendronate have not been
performed. The correlation between endoscopic findings and the relative
incidence of clinically-serious upper GI events that may be observed with
different products has not fully been established.
About the Discontinuation Study
A second study presented by Dr. Rick Adachi, Professor, Department of
Medicine, McMaster University and St. Joseph's Hospital evaluated
66 postmenopausal, osteoporotic women who had previously discontinued therapy
with alendronate due to upper GI complications within the first three months
of treatment. This three-month, randomized, double-blind, placebo-controlled
trial assessing the ability of these patients to continue treatment when
taking risedronate found that 89 percent of the women were able to tolerate
risedronate. Discontinuation rates due to upper GI adverse events were
11 percent for risedronate and 16 percent for placebo; overall, adverse events
were comparable to placebo. The study included patients with a history of
H2-blocker/proton pump-inhibitor use, who often experience GI complications
when undergoing bisphosphonate therapy.
"Tolerability during the first few months of therapy is a key marker for
patient satisfaction and compliance," said Dr. Adachi. "The favorable
tolerability of risedronate in this study is encouraging. It suggests that
intolerance due to GI adverse events with one bisphosphonate does not preclude
use with another bisphosphonate."
The Importance of Safety
Clinical data for risedronate show that it can provide effective treatment
and have a good tolerability profile. This is essential to managing this
"There is a great need for osteoporosis treatments that work to prevent
and treat osteoporotic fractures, and do so with a good tolerability profile,"
said Dr. Adachi. "A medication associated with a low incidence of gastric
ulcers can help patients stick with their treatment regimen and help optimize
their chances for successful treatment. The data on risedronate suggest that
it offers this benefit."