Premium
N‐bisphosphonates cause gastric epithelial injury independent of effects on the microcirculation
Author(s) -
Marsha D. Wallace,
Dicay,
McKnight,
Bastaki,
; Blank
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00658.x
Subject(s) - medicine , infiltration (hvac) , nitric oxide , microcirculation , stomach , epithelium , gastric mucosa , pathology , pharmacology , gastroenterology , physics , thermodynamics
Background: Nitrogen‐containing bisphosphonates have been shown to be effective for the treatment of osteoporosis and Paget’s disease of bone. Unfortunately, these drugs also have the capacity to irritate the upper gastrointestinal mucosa. In this study we investigated the ability of alendronate and pamidronate to directly damage the gastric epithelium and attempted to determine whether these drugs caused injury through gastric microcirculatory alterations. Methods: An ex vivo gastric chamber model was used. Effects of topically applied alendronate and pamidronate on transmucosal potential difference and epithelial integrity (histology) were determined. Also, the effects of agents capable of preventing microvascular injury in the stomach (PGE 2 and two nitric oxide donors) were examined for their ability to prevent gastric injury induced by the two N‐bisphosphonates. Results: Alendronate and pamidronate caused a concentration‐dependent decrease in transmucosal potential difference, widespread epithelial injury and infiltration of neutrophils into the mucosa. PGE 2 and the two nitric oxide donors did not prevent the changes in potential difference or the epithelial injury, but did reduce neutrophil infiltration. Significant release of PGE 2 into the lumen was observed following application of the two bisphosphonates, but neither drug altered mucosal blood flow. Conclusions: These results suggest that these N‐bis‐ phosphonates directly damage the gastric epithelium independent of actions on the microvasculature.