Adverse Effects of Long-Term Omeprazole Use

Established Adverse Effects with Strong Evidence

The American Geriatrics Society suggests that PPIs lower gastric acid, decreasing calcium absorption and potentially increasing fracture risk through this mechanism 3
Meta-analysis of 24 observational studies demonstrates a 20% increased risk of hip fracture with long-term PPI use, with a relative risk of 1.20 and 95% confidence interval of 1.14-1.28 1
PPIs increase susceptibility to gastroenteritis and other enteric infections due to reduced gastric acid barrier, with a significant association found in vulnerable populations 1, 2
Meta-analysis shows a 71% higher risk of hypomagnesemia with PPI use after ≥3 months of therapy, with an adjusted odds ratio of 1.71 and 95% confidence interval of 1.33-2.19 1, 2
Reduced gastric acid impairs absorption of non-heme iron specifically, leading to a dose-dependent association between continuous PPI use and iron deficiency 1
Rebound acid hypersecretion is common after discontinuation, lasting 2-6 months as a physiological response to secondary hypergastrinemia 1, 2

The American College of Gastroenterology recommends that patients without definitive indications for chronic PPI should be considered for trial of de-prescribing 1, 2
Monitoring recommendations include checking magnesium levels before starting and periodically during long-term therapy, as well as assessing vitamin B12 status after 3+ years of continuous use 2
Patients with pre-existing fracture risk factors should be monitored for bone health, with a significant association found between long-term PPI use and increased risk of fractures 1