iuretics and Bone Loss in Rats With Aldosteronism eter

OBJECTIVES We hypothesized that the increased urinary Ca and Mg excretion and bone loss that accompanies aldosteronism is aggravated with furosemide and is attenuated by spironolactone. BACKGROUND 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. METHODS In ageand gender-matched, untreated controls, four weeks of aldosterone/salt treatment (ALDO/salt, 0.75 g/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 Ca and Mg excretion; plasma-ionized [Ca ]o and [Mg ]o, K , and parathyroid hormone (PTH); and bone mineral density (BMD) in the femur. RESULTS The ALDO/salt increased (p 0.05) urinary Ca and Mg excretion (4,969 1,078 and 3,856 440 g/24 h, respectively) compared with controls (896 138 and 970 137 g/24 h, respectively); furosemide co-treatment further increased (p 0.05) urinary Ca and Mg excretion (6,976 648 and 6,199 759 g/24 h, respectively), whereas spironolactone co-treatment attenuated (p 0.05) these incremental losses (4,003 515 and 3,915 972 g/24 h). Plasma [Ca ]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. CONCLUSIONS In aldosteronism, hypercalciuria and hypermagnesuria and accompanying decrease in plasmaionized [Ca ]o and [Mg ]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. (J Am Coll Cardiol 2005;46:142–6) © 2005 by the ublished by Elsevier Inc. doi:10.1016/j.jacc.2005.03.055