The Association Between Prolonged Proton Pump Inhibitors Use and Bone Mineral Density

Chronic use of proton-pump inhibitors (PPIs) has become a mainstay of therapy in common gastrointestinal diseases. A causal relationship between chronic PPI use and development of osteoporosis remains unproven. The aim of this study was to determine whether PPI users are more likely to develop alterations in bone density.

In an analytical cross sectional study, patients who used PPIs for more than 2 years because of long-term gastroesophageal reflux disease (GERD) were recruited. PPI users were healthy people except for GERD. The compression group was randomly derived from an age-, sex- and physical activity-matched group from a healthy population in the National Registry of Osteoporosis who had not used PPIs in the previous 2 years. Bone mineral density was measured with dual-energy X-ray absorptiometry. Data regarding BMD and bone mineral content (BMC) of three regions: femoral neck, total hip, and the lumbar spine (L1-L4) were gathered and recorded. The World Health Organization (WHO) classification was used for definition of osteopenia and osteoporosis.

A total of 394 participants (133 PPI users and 261 comparison group) were enrolled. The median duration of PPI use was 6.7 (2-31) years. The mean age ± SD of PPI users and comparison group was 48.38 ± 11.98 and 47.86 ± years, respectively (P = 0.681). There was no significant difference in baseline characteristics and age distribution between the two groups. The BMC levels were significantly lower in PPI users in all three regions: lumbar spine, total hip, and femoral neck (P<0.001). There were no significant differences in the T-scores between the two groups except for femoral neck (P<0.001). Osteoporosis in femoral neck was significantly higher in PPI users than in comparison group.

This study showed that long-term use of PPIs is associated with lower BMC and higher rate of osteoporosis in the femoral neck. However, more studies with longitudinal evaluation should be performed to clarify this causal relationship. Until then, it is advised not to overuse PPIs because of the possible increase in risk of osteoporosis and the risk of fractures. We also recommend using the BMC levels as a quantitative measure in addition to T scores in analysis and reporting similar studies.