Background Pyrophosphate arthritis (PPA) has been associated to hypomagnesemia, therefore, serum magnesium (sMg) levels determination is recommended by EULAR (1). Eventhough thiazide diuretics are considered as a risk factor for hypomagnesemia; paradoxically, an absence of association has been described between PPA and thiazides, and present with loop diuretics (2), but the authors lacked levels of sMg for statistical analysis and the diagnosis was only clinical and performed by general practitioners; nonetheless, the authors advised considering the withdrawal of loop diuretics in patients with PPA.
Objectives To evaluate sMg levels in patients with PPA and controls, as well as the impact of treatment with diuretics and administered doses on sMg.
Methods Prospective recruitment, transversal design, case-control study (patients with PPA with microscopy diagnosis of synovial fluid) and controls (paired by age and gender, absence of radiographic chondrocalcinosis and synovial fluid negative for pyrophosphate crystals). sMg levels were obtained, as well as data regarding use of diuretics, type and doses at time of analysis. The rate of prescription of diuretics, type and doses (cut-off points ≤40mg/day equivalent of Furosemide and ≤12.5mg/day equivalent of hydrohlorothiazide) associated to sMg levels and presence of hypomagnesmia (sMg<1.7 mg/dL) were also analyzed.
Results 602 patients (53% male, median age 73±9 years), with 323 cases and 279 controls were analyzed. The prescription of any diuretic and thiazide diuretics was more frequent in cases than in controls: 40.2% vs 25.4% and 15.8% vs 9.7%, respectively and both p<0.01. The levels of sMg and rate of hypomagnesemia were different in cases and controls: 2.00±0.29 vs 2.08±0.23 mg/dL, p<0.01 and 7.2% vs 14.0%.
Patients on diuretics had lower sMg levels than patients without them (1.99±0.32 vs 2.06±0.24, p<0.01), but this effect was only observed in patients on thiazides (1.84±0.31 vs 2.08±0.29). The rate of hypomagnesemia was higher in patients on diuretics (22.6% vs 5.0%; OR 5.5; 95%CI 3.1-9.8; p<0.01), and associated again with use of thiazides (36.0% vs 13.4%; OR 3.6; 95% CI 1.8-7.5; p<0.01).
The analysis of diuretic doses showed that the rate of hypomagnesemia for patients without diuretics was not statistically different than that of patients on loop diuretics with either low or high doses, or patients on low-dose thiazides (5, 20 and 13% respectively), but was different when compared to high-dose thiazides (68%, p<0.01).
Conclusions sMg levels and hypomagnesemia are associated to high-dose thiazide use, but not to lower doses or prescription of loop diuretics, what is concordant with pharmacodynamics and pharmacokinetics. Patients with PPA use thiazides more frequently than controls, showing lower sMg levels and higher rates of hypomagnesemia when compared to controls and patients with loop diuretics.
Zhang W, et al. Ann Rheum Dis 2011
Rho YH, et al. Rheumatology 2012
Disclosure of Interest S. Chinchilla: None declared, I. Urionagüena: None declared, F. Perez-Ruiz Consultant for: AstraZeneca, Menarini, Pfizer, Speakers bureau: AstraZeneca, Menarini