The Association of Diuretics and Proton Pump Inhibitors With Chondrocalcinosis

Objective Hypomagnesemia increases the risk of chondrocalcinosis and calcium pyrophosphate disease. We examined whether the use of drugs that can cause hypomagnesemia, diuretics and proton pump inhibitors (PPIs), increases the risk of chondrocalcinosis. Methods Participants in the Multicenter Osteoarthritis (MOST) Study obtained weight‐bearing knee radiographs, and their medication use was recorded at baseline and 30‐, 60‐, 84‐, and 144‐month examinations. We read radiographs serially for chondrocalcinosis and characterized incident chondrocalcinosis when it first appeared. We classified diuretic use as thiazide, loop, and other. To test drug effects on incident chondrocalcinosis at each interval (eg, 30‐60 months), we excluded persons with chondrocalcinosis at the interval’s beginning. For each drug, we evaluated exposure at the beginning and end of the interval. We conducted knee‐based analyses using Bayesian mixed‐effects discrete time survival models adjusted for age, sex, body mass index, radiographic osteoarthritis, race, and clinic site. Results Of 5272 knees, 196 developed chondrocalcinosis. Thiazide use (21.7% of examinations) and PPI use (13.7%) were common. Neither loop nor other diuretic use was associated with incident chondrocalcinosis. Thiazide use at the beginning and end of the interval of incidence conferred a high risk (hazard ratio [HR] = 2.18; 95% confidence interval [CI] 1.23‐3.89), but use at the beginning of the interval was not associated with risk (HR = 1.04). PPI use at the interval’s beginning increased risk of chondrocalcinosis (HR = 2.29; 95% CI 1.37‐3.79). Conclusion Thiazide diuretics, but not other diuretics, and PPI use probably increase the risk of chondrocalcinosis. These findings may have important clinical implications.