We hypothesized that the increased urinary Ca2+ and Mg2+ excretion and bone loss that accompanies aldosteronism is aggravated with furosemide and is attenuated by spironolactone.
Furosemide, a loop diuretic, is commonly used in patients with congestive heart failure (CHF), in which chronic, inappropriate (dietary Na+) elevations in plasma aldosterone (ALDO) and a catabolic state that includes bone wasting are expected.
In age- and gender-matched, untreated controls, four weeks of aldosterone/salt treatment (ALDO/salt, 0.75 μg/h + 1% NaCl/0.4% KCl in drinking water), four weeks of ALDO/salt + furosemide (40 mg/kg in prepared food), and four weeks of ALDO/salt + furosemide + spironolactone (200 mg/kg/day in divided doses by twice-daily gavage), we monitored: 24-h urinary Ca2+ and Mg2+ excretion; plasma-ionized [Ca2+]o and [Mg2+]o, K+, and parathyroid hormone (PTH); and bone mineral density (BMD) in the femur.
The ALDO/salt increased (p < 0.05) urinary Ca2+ and Mg2+ excretion (4,969 ± 1,078 and 3,856 ± 440 μg/24 h, respectively) compared with controls (896 ± 138 and 970 ± 137 μg/24 h, respectively); furosemide co-treatment further increased (p < 0.05) urinary Ca2+ and Mg2+ excretion (6,976 ± 648 and 6,199 ± 759 μg/24 h, respectively), whereas spironolactone co-treatment attenuated (p < 0.05) these incremental losses (4,003 ± 515 and 3,915 ± 972 μg/24 h). Plasma [Ca2+]o was reduced (p < 0.05) at week 4 ALDO/salt + furosemide and was accompanied by hypokalemia (<3.4 mmol/l) that were rescued by spironolactone. Plasma PTH was increased (p < 0.05) compared with controls (30 ± 4 vs. 11 ± 3 pg/ml, respectively), whereas BMD was decreased (p < 0.05) with ALDO/salt and ALDO/salt + furosemide, but not with spironolactone co-treatment.
In aldosteronism, hypercalciuria and hypermagnesuria and accompanying decrease in plasma-ionized [Ca2+]o and [Mg2+]o lead to hyperparathyroidism that accounts for bone wasting. Furosemide exaggerates these losses, whereas its combination with spironolactone attenuates these responses to prevent bone loss.