Proton pump inhibitors independently associated with an increased risk of falls in older Irish adults

Abstract Background Recent studies have shown an association between PPI use and increased risk of falls. A meta-analysis of eight studies (n=367,068) identified a 27% increased falls risk in PPI users. Potential mechanisms include reduced gut absorption of calcium, magnesium and other nutrients, altered gut microbiome and possible effects on muscle function. We aimed to explore the association between PPI use and falls risk in older adults. Methods Participants were adults aged >60 yrs from the TUDA study. Exclusion criteria were MMSE <24, history of stroke and current or long-term steroid use. The relationship between PPI use and self- reported falls in the last year was explored in multinomial regression adjusting for age, sex, BMI, timed up and go (TUG), diabetes, vitamin D, serum B12, parathyroid hormone, depression, dizziness on standing, ischemic heart disease, MMSE, medications (antihypertensives, loop diuretics, NSAIDs, benzodiazepines, opioids, Z drugs). We also explored for an association in those with normal TUG (<10 seconds) and in high dose PPI users versus non-users. Results 3701 participants, mean age 73.1, 68.8% female, 32.6% fallen in last year, 35.3% PPI users. PPI use was associated with an increased risk of falls before and after multivariate adjustment (OR 1.29 CI 1.11-1.50, P<0.001). In a subsample (n=3059), high dose PPI users versus non-users had a greater risk of falls (OR 1.43, CI 1.17-1.75, p=0.0003). In those with normal TUG, the overall relationship remained significant (OR 1.34, CI 1.07-1.69, p=0.011) and also in high dose PPI users versus non-users (OR 1.89, CI 1.39-2.58, p<0.0001). Conclusion Overall, PPI users had a 29% increased risk of falls independent of numerous factors and this remained significant in those without physical frailty. Furthermore, risk was greater risk in high dose PPI users. Future studies are needed to further explore this and the potential mechanisms.