Diuretics and Bone Loss in Rats With Aldosteronism

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 (