New Study Links Chronic Proton Pump Inhibitor Use and Bone Health in Men

New research found that chronic use of proton pump inhibitors (PPIs), commonly prescribed for acid-related gastrointestinal conditions, has been linked to increased bone fragility in men. They are not observed in women but only men despite adjustment of bone mineral density and little data exist regarding the impact on bone microarchitecture. The study results were published in The Journal of Clinical Endocrinology & Metabolism.

Research in the past has linked PPIs to increased bone fragility. However, there is uncertainty in the data regarding the bone density and the long-term use of PPIs and also on the microarchitectural quality of the bone. Hence researchers conducted a study to assess whether trabecular bone microarchitecture, as measured by the trabecular bone score (TBS), is negatively impacted by chronic PPI use. Additionally, the study aimed to explore the association between PPI use and bone mineral density (BMD) as a secondary endpoint.

The study utilized data from the 2005-2008 cycles of the National Health and Nutrition Examination Survey (NHANES) which is a large population-based survey. A total of 7,478 participants (3,961 men and 3,517 women) were included, with each subject undergoing lumbar spine dual-energy X-ray absorptiometry (DXA) scans. These scans were used to calculate TBS, a measure of trabecular bone microarchitecture, via specialized software. Multivariable linear regression analyses were performed, stratified by sex, to assess the relationship between chronic PPI use and both TBS and BMD. The analyses were adjusted for relevant confounding factors, including age, body mass index (BMI), and lifestyle variables.

Results:

• The study found that in men, chronic PPI use was associated with a significant decline in bone health.
• Specifically, men using PPIs had lower TBS values (-0.039, 95% CI: [-0.058, -0.020], p<0.001), indicating a deterioration in bone microarchitecture.
• They also had lower T-scores, which reflect BMD, at the lumbar spine (-0.27, 95% CI: [-0.49, -0.05], p=0.018), total hip (-0.20, 95% CI: [-0.39, -0.01], p=0.038), and femoral neck (-0.21, 95% CI: [-0.42, -0.01], p=0.045).
• Importantly, the association between chronic PPI use and poorer TBS remained statistically significant even after adjusting for BMD at both the lumbar spine and femoral neck (-0.026, 95% CI: [-0.039, -0.012], p=0.001).
• Conversely, no significant associations were found between chronic PPI use and TBS or BMD in women suggesting men may be more susceptible to the bone-degrading effects of long-term PPI use than women.

Thus, the findings indicate that chronic PPI use is linked to poorer trabecular bone quality in men, even when BMD is taken into account. No similar association was observed in women, raising questions about sex differences in how chronic PPI use impacts bone health. The study underscores the need for clinicians to carefully monitor bone health in male patients on long-term PPI therapy, particularly those at risk for osteoporosis or other bone-related conditions.

Findings:

Fabio Bioletto, Alessia Pusterla,et al, Sex-specific association of chronic proton pump inhibitor use with reduced bone density and quality, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae598, https://doi.org/10.1210/clinem/dgae598