Proton pump inhibitors (PPIs), such lansoprazole, are drugs given to patients to reduce excessive stomach acid production. PPIs are one of the most widely used medicines in the world and in 2017 there were more than 59 million PPI prescriptions in England alone.
Recent studies have reported an increased risk of bone fractures in patients on long-term PPI use. The mechanism of action is unclear as another group of drugs called histamine-2-receptor antagonists (H2RAs) which also reduce stomach acid production, have no effect on fracture risk.
Our pilot data has shown that different PPIs have varying effects on the activity of PHOSPHO1, a bone specific enzyme required for bone mineralisation. Furthermore, H2RAs have no effect on PHOSPHO1 function. This therefore suggests a new mechanism of PPI action. Here we will use the UK BioBank to determine whether patients on different PPI drugs are more or less susceptible to bone fractures.
This work has the potential to improve human health by reducing bone fracture risk with chronic use of PPIs. This is particularly important for the quality of life in our ageing population who are at increased risk of bone fractures.