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Abstract

Previous studies have shown that the bisphosphonates (BP) vary in their damaging effect on the gastric mucosa, and endoscopy scores (erosions or erosions plus ulcers) after 1 and 2 weeks use of BP were significantly lower in H. pylori-positive versus -negative subjects. The mechanism of this damaging effect of BP and the interaction with H. pylori is unknown. As part of a separately reported study of the incidence of gastric damage after 2 weeks of treatment of healthy female postmenopausal volunteers with risedronate (5 mg/day) or alendronate (10 mg/day), gastric aspirates were taken at the time of the baseline esophagogastroduodenoscopy (EGD), and again at 1 and 2 weeks after daily intake of a BP At the time of the third EGD, when the volunteers had been on risedronate or alendronate for 2 weeks, antral biopsies were taken from normal-appearing mucosa. Gastric juice and antral biopsies were assessed for their concentration of the cytokines interleukin-la (IL-1alpha), IL-8, IL-13, and epidermal growth factor (EGF). H. pylori, the use of BP, and development of gastric mucosal lesions had no effect on gastric mucosal concentrations of IL-1alpha, IL-13, or EGF. In contrast, the concentration of IL-8 in antral mucosal biopsies of volunteers given BP for 2 weeks was higher in the presence than in the absence of an H. pylori infection and was increased further in those who develop lesions associated with the use of BP. There was no correlation between gastric mucosal and gastric juice concentrations of IL-8. Gastric juice concentrations of IL-8 and EGF were not affected by H. pylori status, the use of BP, or the development of lesions. However, gastric juice concentrations of IL-1alpha were numerically lower in those who were negative for H. pylori with no mucosal lesions (Hp-L-), intermediate in those who were H. pylori-negative with lesions (Hp-L+), and highest in those who were positive for H. pylori and had lesions (Hp+L+). The gastric juice concentration of IL-13 was threefold higher in the absence than in the presence of H. pylori, and the relative abundance of IL-13 was: Hp-L- >Hp-L+ >Hp+L(-1) >Hp+L+. The prostaglandin E2 concentration in gastric antral biopsies was similar in the four groups and was unchanged with the in vitro biopsy incubation with celecoxib. We speculate that the higher gastric endoscopy scores observed with the use of BP in H. pylori negative as compared with H. pylori positive individuals is due to their lower mucosal concentration of IL-8 as well as the lower gastric juice concentration of IL-1alpha and higher concentration of IL-13.

Biomarkers in Patients with Gastric Inflammation: A Systematic Review

“…In the former studies, most investigations were designed as cross-sectional studies with the exception of 1 case-controlled study, 1 randomized study, and 3 prospective studies. Among 50 selected citations, 32 reports discussed IL-8 as a biomarker for gastric inflammation [65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96], 11 reports described IL-1 as a biomarker for gastric inflammation [66, 69, 77, 82, 92,97,98,99,100,101], and 7 reports focused on TNF-α as a marker for gastric inflammation [71, 77, 81, 82, 90, 91, 102] (fig. 1).…”

“…Namely, successful H. pylori eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL-8 levels and histological gastric inflammation, suggesting that certain peptide-immune interactions in the gastric mucosa exist in H. pylori infection [70]. Thompson et al [101] reported the association of increased gastric concentrations of mucosal IL-8 and gastric juice IL-1α in H. pylori infection.…”

Oral Treatment With Bisphosphonates of Osteoporosis Does Not Increase the Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials

“…In vitro studies suggest that the mucosal damage is produced through topical irritant effects on the gastric epithelium (60,61). It is also described that BPs are competitively displacing the phospholipids from the mucus gel layer, therefore the mucosal hydrophobic barrier is attenuated and mucosal healing is hindered (62)(63)(64).…”

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“…In vitro studies suggest that the mucosal damage is produced through topical irritant effects on the gastric epithelium (60,61). It is also described that BPs are competitively displacing the phospholipids from the mucus gel layer, therefore the mucosal hydrophobic barrier is attenuated and mucosal healing is hindered (62)(63)(64).…”