An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae.
OBJECTIVE
The nitrogen-containing bisphosphonates alendronate and risedronate have been reported to have upper gastrointestinal (GI) safety and tolerability profiles comparable to those of placebo. Nevertheless, both agents have demonstrated similar potential for irritation of gastric mucosa at high doses in preclinical studies. The present study compared the potential for alendronate and risedronate to produce endoscopic upper GI mucosal irritation using the highest approved dosage regimens for the two agents.


METHODS
This was a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial in which a total of 235 patients (men or postmenopausal women, aged 45-80 yr) with normal upper GI endoscopy at baseline received 28-day treatments with the following: alendronate 40 mg/day (N = 90), risedronate 30 mg/day (N = 89), placebo (N = 36), or placebo with aspirin 650 mg q.i.d. for the last 7 days (N = 20). Endoscopy was repeated on day 29 using standardized scoring scales.


RESULTS
After 28 days of treatment, the alendronate and risedronate groups had comparable mean gastric and duodenal erosion scores that were significantly lower than those of the aspirin group. Esophageal scores were comparable in all groups. Gastric ulcers and/or large numbers of gastric erosions occurred in approximately 3% of alendronate and risedronate patients versus 60% with aspirin. Both bisphosphonates were clinically well tolerated.


CONCLUSIONS
The potential for gastroduodenal irritation is similar for alendronate and risedronate and is markedly less than for aspirin. The findings of this study, together with the large placebo-controlled clinical trial experience with both agents and extensive epidemiological data for alendronate, suggest that the risk for clinically important gastric irritation with these bisphosphonates is very low, even at the highest available doses.
Lanza
F
F
Houston Institute for Clinical Research, Texas 77074, USA.
Schwartz
H
H
Sahba
B
B
Malaty
H M
HM
Musliner
T
T
Reyes
R
R
Quan
H
H
Graham
D Y
DY
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D004311:Double-Blind Method; D016099:Endoscopy, Gastrointestinal; D004945:Esophagoscopy; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000068296:Risedronic Acid; D013997:Time Factors
D002121:Calcium Channel Blockers; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate