The Effect of Proton Pump Inhibitors on Bone Mineral Density at Specific Anatomical Sites: A Systematic Review and Meta-Analysis.

There have been some concerns about the potential adverse consequences of proton pump inhibitors (PPIs) on bone health, specifically with respect to bone mineral density (BMD). The objective of the present investigation was to evaluate the impact of PPIs on BMD in the lumbar spine, femoral neck, and total hip regions. On the basis of PRISMA, a systematic review and meta-analysis were performed. PubMed, Scopus, Cochrane Library, and Google Scholar were used to find eligible observational studies published between January 2010 and January 2025. The ROBINS-I tool was employed to evaluate potential for bias, and studies with critical bias were excluded. To synthesize the data, random-effects models were utilized, and the I 2 statistic was used to evaluate heterogeneity. The sensitivity analyses and publication bias were also performed. A systematic review and quantitative synthesis used 20 and seven records, respectively, of 170 records screened. The comprehensive pooled analysis revealed that the decrease in BMD with the use of PPIs was modest yet statistically significant (SMD -0.15, 95% CI -0.21 to 0.09) alongside a substantial degree of heterogeneity (I 2 = 93.6%). Subgroup analysis demonstrated that there were significant decreases at the femoral neck (SMD -0.27, 95% CI -0.46 to -0.09), but not at the lumbar spine or the total hip. The funnel plot analysis indicated a certain level of asymmetry, and the sensitivity analysis indicated that the results were mostly robust; unless the study that excluded one outlier was used in the analysis, then the lumbar spine results would change. The use of PPIs is related to a significant but relatively small decrease in BMD, most obvious at the femoral neck, although findings across anatomical locations are heterogeneous. The results of this study support the cautious use of PPIs in all people at risk of osteoporosis and the need to conduct a high-quality prospective study to understand site-specific effects in the future.