ArticleMedicine2026
Proton pump inhibitors use and the risk of osteoporosis and fractures: A two-sample Mendelian randomization study.
Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
3 authors.
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Abstract
The causal relationship between proton pump inhibitor (PPI) use and bone health outcomes remains uncertain. This study employs a Mendelian randomization (MR) approach to investigate the potential causal association between PPI use and the risk of osteoporosis and fractures. We selected 4 representative PPIs, including omeprazole, esomeprazole, lansoprazole, and rabeprazole, for our study. Bone health outcomes were evaluated through femoral neck bone mineral density (BMD), lumbar spine BMD, and the prevalence of osteoporosis and fracture across various anatomical sites, including the upper arm and shoulder, wrist and hand, lumbar spine and pelvis, femur, and lower leg and ankle. To evaluate PPI exposure and bone health outcomes, we utilized summary statistics derived from genome-wide association studies conducted in European ancestry populations. Primary causal estimates were derived using the inverse-variance weighting (IVW) approach, supplemented by MR-Egger, weighted median, and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods. To strengthen the robustness of our findings, we conducted sensitivity analyses encompassing assessments of heterogeneity, horizontal pleiotropy, and leave-one-out analyses. Lansoprazole demonstrated a significant positive causal effect on femoral neck BMD (IVW: β = 0.137, 95% confidence interval: 0.063-0.210, P = 2.73E-04), whereas no statistically significant effects were observed for lansoprazole on lumbar spine BMD, osteoporosis, or fracture risk. Esomeprazole showed a marginal causal association with an elevated risk of femur fracture (IVW: odds ratio = 1.049, 95% confidence interval: 1.004-1.096, P = .031); however, this association lost statistical significance following Bonferroni correction. Its effects on BMD, osteoporosis, and fractures at other anatomical sites remained nonsignificant. No causal associations with BMD, osteoporosis, or fracture risk were identified for either omeprazole or rabeprazole. Sensitivity analyses further reinforced the robustness and reliability of these findings. This MR analysis found no compelling evidence to support a causal association between PPI use and the risk of osteoporosis or fractures.
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