Sex-specific association of chronic proton pump inhibitor use with reduced bone density and quality

Abstract Context Chronic use of proton pump inhibitors (PPIs) has been associated with an increase in bone fragility. However, evidence on the effect of chronic PPI use on bone density is conflicting, and data on bone microarchitectural quality are scarce. Objective The primary aim of this study was to evaluate whether trabecular bone microarchitecture, assessed by trabecular bone score (TBS), is altered in chronic PPI users. The association between PPI use and bone density was also evaluated as a secondary endpoint. Methods We extracted individual patient data from the 2005-2008 cycles of the population-based National Health and Nutrition Examination Survey (NHANES), in which lumbar spine dual-energy X-ray absorptiometry (DXA) scans were acquired. TBS values were calculated from DXA images using a dedicated software. Multivariable linear regression analyses stratified by sex were performed to evaluate the association of chronic PPI use with TBS and bone mineral density (BMD), adjusting for relevant confounders. Results A total of 7478 subjects were included (3961 men, 3517 women). After adjustment for relevant confounders, chronic PPI use was associated with a worse bone health profile in men, with lower TBS (-0.039, 95%CI:[-0.058, -0.020], p<0.001), lumbar spine T-score (-0.27, 95%CI:[-0.49, -0.05], p=0.018), total hip T-score (-0.20, 95%CI:[-0.39, -0.01], p=0.038), and femoral neck T-score (-0.21, 95%CI:[-0.42, -0.01], p=0.045). Notably, the association between chronic PPI use and degraded TBS remained statistically significant even after further adjustment for BMD at lumbar spine and femoral neck (-0.026, 95%CI:[-0.039, -0.012], p=0.001). In contrast, no significant association was observed between chronic PPI use and either TBS or BMD in women. Conclusions Chronic PPI use is associated with degraded trabecular bone quality in men, even after adjustment for BMD. No association was observed in women.