14 day endoscopy study comparing risedronate and alendronate in postmenopausal women stratified by Helicobacter pylori status.
OBJECTIVE
Bisphosphonates are effective treatment for osteoporosis but have been associated with gastrointestinal (GI) mucosal injury. This study compared the incidence of gastric ulcers after treatment with risedronate, a pyridinyl bisphosphonate, or alendronate, a primary amino bisphosphonate, in healthy postmenopausal women stratified by Helicobacter pylori status.


METHODS
Subjects were randomized to receive risedronate 5 mg (n = 318) or alendronate 10 mg (n = 317) daily for 14 days. Endoscopy and evaluator-blind assessments of the esophageal, gastric, and duodenal mucosa were performed at baseline and on Days 8 and 15.


RESULTS
Overall, gastric ulcers > or = 3 mm were observed in 18 (6.0%) of 300 evaluable subjects in the risedronate group and 36 (12.1%) of 297 in the alendronate group during treatment (p = 0.013). On Day 8, the incidences of gastric ulcers in the risedronate and alendronate groups were 3.6% and 6.6%, respectively (p = 0.133), and on Day 15, they were 3.3% and 8.7% (p = 0.008). The incidence of gastric ulcers was not affected by H. pylori status. Mean gastric endoscopy scores at Days 8 and 15 were significantly lower in the risedronate group than in the alendronate group (p < 0.001). Mean esophageal and duodenal endoscopy scores were similar in the 2 groups at Days 8 and 15. When the treatment groups were combined, gastric endoscopy scores were significantly higher among H. pylori negative than H. pylori positive subjects at Days 8 and 15 (p < 0.05). Upper GI adverse events were reported by 18 (5.7%) subjects in the risedronate group (19 events) and 28 (8.8%) subjects in the alendronate group (32 events). Symptoms did not predict the presence of mucosal damage.


CONCLUSIONS
Risedronate was associated with a significantly lower incidence of gastric ulcers than alendronate. H. pylori infection did not increase the incidence of bisphosphonate related gastric ulcers. The findings from this 14 day study in healthy volunteers support the hypothesis that bisphosphonates may differ from one another in their potential to produce upper GI mucosal damage.
Thomson
Alan B R
AB
University of Alberta, Edmonton, Canada.
Marshall
John K
JK
Hunt
Richard H
RH
Provenza
J Mark
JM
Lanza
Frank L
FL
Royer
Mary G
MG
Li
Zhengqing
Z
Blank
Marion A
MA
D000368:Aged; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D000704:Analysis of Variance; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D005773:Gastroscopy / Q000379:methods*; D016481:Helicobacter Infections / Q000150:complications / Q000473:pathology*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011336:Probability; D012016:Reference Values; D000068296:Risedronic Acid; D018570:Risk Assessment; D016037:Single-Blind Method; D013276:Stomach Ulcer / Q000150:complications / Q000473:pathology*; D016896:Treatment Outcome
D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate