PPI-induced changes in plasma metabolite levels influence total hip bone mineral density in a UK cohort.

Proton pump inhibitors (PPIs) are amongst the most used drugs in the UK. PPI use has been associated with decreased bone mineral density (BMD) and increased fracture risk, although these results have been inconsistent. We hypothesised that PPI could modulate BMD by altering gut and/or host systemic metabolic environments. Using data from more than 5,000 British male and female individuals, we confirmed that PPI use is associated with decreased lumbar spine and total hip BMD. This effect was not mediated through the gut microbiome. We suggest here that PPI use may influence total hip BMD, both directly and indirectly, via plasma metabolites involved in the sex hormone pathway. This article is protected by copyright. All rights reserved.