Diuretics and bone loss in rats with aldosteronism.
OBJECTIVE
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.


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 age- and gender-matched, untreated controls, four weeks of aldosterone/salt treatment (ALDO/salt, 0.75 microg/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.


RESULTS
The ALDO/salt increased (p < 0.05) urinary Ca2+ and Mg2+ excretion (4,969 +/- 1,078 and 3,856 +/- 440 microg/24 h, respectively) compared with controls (896 +/- 138 and 970 +/- 137 microg/24 h, respectively); furosemide co-treatment further increased (p < 0.05) urinary Ca2+ and Mg2+ excretion (6,976 +/- 648 and 6,199 +/- 759 microg/24 h, respectively), whereas spironolactone co-treatment attenuated (p < 0.05) these incremental losses (4,003 +/- 515 and 3,915 +/- 972 microg/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.


CONCLUSIONS
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.
Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Peter H
PH
Law
Yao
Y
Sun
Syamal K
SK
Bhattacharya
Vikram S
VS
Chhokar
Karl T
KT
Weber
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood / Q000652:urine*; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D006929:Hyperaldosteronism / Q000097:blood / Q000652:urine*; D008274:Magnesium / Q000097:blood / Q000652:urine*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D011188:Potassium / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology*
D004232:Diuretics; D010281:Parathyroid Hormone; D013148:Spironolactone; D005665:Furosemide; D008274:Magnesium; D011188:Potassium; D002118:Calcium