Abstract
OBJECTIVES: Proton pump inhibitors (PPIs) are among the most widely prescribed drugs for long-term suppression of gastric acid. Though generally considered safe, increasing evidence links their use to altered bone metabolism. This systematic review investigates the hypothesis that PPI-induced inhibition on PHOSPHO1-a bone-specific phosphatase- impairs bone mineralisation. METHODS: A systematic electronic search was conducted for experimental studies from January 2000 to January 2025. The screening and selection followed PRISMA guidelines. RESULTS: Of 20 articles identified, 3 met the inclusion criteria: two in-vitro studies and one combining both in-vitro and in-vivo data. All three examined the effects of PPIs on bone formation and consistently reported significantly reduced minerallization capacity. CONCLUSION: The review suggests that PPIs appear to inhibit PHOSPHO1 activity, potentially impairing early-stage bone mineralisation. However, due to the limited number of studies, these findings should be interpreted with caution, and further research is warranted.