The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture—results of a large observational cohort study

Summary Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08–2.23, p=0.018). This highlights the importance of monitoring PPI use, especially in older adults.

Purpose Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults.

Methods Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular fltration rate (eGFR)<30 ml/min and serum calcium>2.5 mmol/l were excluded to avoid hyperpar-athyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defned as a parathyroid hormone (PTH)>65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism.

Results A total of 4139 participants met the inclusion criteria, of whom 37.8% (n=1563) were taking PPI medication. PPI use was identifed in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p<0.001) and had a higher prevalence of hyperpar-athyroidism (17.8 vs 11.0%, p<0.001). In those taking calcium supplements (but not in non-users), PPI use was signifcantly associated with hyperparathyroidism (OR 1.56, CI 1.08–2.23, p=0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities.

Discussion The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.