↓ Absorption of calcium and magnesium → ↑ risk of osteoporosis in long-term use→ ↑ risk of fractures in elderly individuals
Because the gastric environment becomes less acidic, dietary calcium remains bound to oxalate, resulting in reduced absorption in the duodenum and jejunum.
The resultant increase in gastric pH leads to increased gastrin formation, which, over time, can lead to hypertrophy of ECL and parietal cells. After chronic use (eg, >8 weeks), abrupt cessation of the PPI can trigger rebound gastric acid hypersecretion by the hyperfunctioning parietal cells, leading to reflux symptoms; PPIs can be slowly tapered to prevent this adverse effect.