Proton-Pump Inhibitors and Risk of Calcium Pyrophosphate Deposition in a Population-Based Study

There are no proven effective medical treatments to prevent calcium pyrophosphate crystal deposition (CPPD). Hypomagnesemia is a known CPPD risk factor. The present study was undertaken to carry out a real-world epidemiologic study on proton-pump inhibitor (PPI) use, which can cause hypomagnesemia, and CPPD risk.

We conducted a time-stratified, propensity score (PS)-matched cohort study using the UK-based IQVIA Medical Research Data. We compared risk of incident CPPD among PPI users versus H₂ blocker users using Cox proportional hazards models. We used greedy matching of incident PPI users 1:1 to incident histamine receptor 2 (H₂ ) blocker users in 1-year cohort accrual blocks. Subjects were censored at time of drug switch. We evaluated incident use of PPI and H₂ blockers prior to incident CPPD using a nested case-control study within the same cohort, matched 1:4 by age and sex using risk-set sampling.

We identified 81,102 PPI and H₂ blocker initiators, with 113 and 63 incident cases of CPPD, respectively. In the case-control study when compared with nonusers, both PPI and H₂ B users had higher risk of incident CPPD, with odds ratios (ORs) of 1.79 (95% confidence interval [95% CI] 1.55-2.07) and 1.52 (95% CI 1.14-2.03), respectively. Incident PPI use was nonsignificantly associated with incident CPPD (hazard ratio 1.03 [95% CI 0.75-1.41]) compared with H₂ blocker use.

In this study using real-world data, incident use of PPIs was not associated with a higher risk of CPPD compared with incident H₂ blocker use, although use of PPI and H₂ blockers had higher risk compared with nonuse.