The role of acidic pH in alendronate-induced esophageal and gastric irritation: An in vitro toxicology investigation of bisphosphonates

Abstract

Aim: Alendronate, a widely used bisphosphonate for osteoporosis treatment, has been associated with esophageal
and gastric irritation. This study investigates the role of acidic pH in alendronate-induced mucosal toxicity using in
vitro toxicology models. Materials and Methods: Human esophageal and gastric epithelial cell lines were exposed
to alendronate under varying pH conditions (7.4, 4.0, and 2.0). Cell viability was assessed using MTT assays,
while oxidative stress markers and pro-inflammatory cytokine levels were measured to evaluate cellular damage.
Microscopic examination was performed to assess morphological changes. Results: Alendronate exposure led to
a significant reduction in cell viability, particularly at acidic pH (2.0), with a 40% decrease compared to neutral
pH (7.4). Increased oxidative stress, as indicated by elevated reactive oxygen species levels, and upregulation
of proinflammatory cytokines (interleukin-6, tumor necrosis factor-alpha) were observed in acidic conditions.
Microscopic analysis revealed cellular shrinkage and membrane disruption, further supporting toxicity. Conclusion:
The findings suggest that acidic pH exacerbates alendronate-induced esophageal and gastric irritation by enhancing
oxidative stress and inflammation. These results highlight the importance of proper administration guidelines, such
as taking alendronate with sufficient water and remaining upright, to minimize mucosal damage. Further research
is needed to explore protective strategies against bisphosphonate-induced toxicity.