Journal
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Volume 330, Issue 1, Pages 1-7Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/00000441-200507000-00001
Keywords
aldosterone; calcium; magnesium; parathyroid hormone; bone loss
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Funding
- NHLBI NIH HHS [R01-HL73043] Funding Source: Medline
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Objective: We hypothesized that aldosteronism is accompanied by hypercalciuria and hypermagnesuria that lead to bone loss, which could be rescued by hydrochlorothiazide and spironolactone. Methods: We monitored 24-hour urinary Ca2+ and Mg2+ excretion; plasma ionized [Ca2+](o), and [Mg2+](o) and plasma K+; and bone mineral density of the femur. The following groups (n = 5 in each group) were studied: age- and gender-matched, untreated controls; controls + 4 weeks hydrochlorothiazide; 4 weeks aldosterone/salt treatment (ALDOST, 0.75 mu g/h and dietary 1% NaCl/0.4% KCl); 4 weeks ALDOST + hydrochlorothiazide (50 mg/kg in prepared food); and 4 weeks ALDOST + hydrochlorothiazide + spironolactone (200 mg/kg day in divided doses by twice-daily gavage). Results: ALDOST increased (P < 0.05) urinary Ca2+ and Mg2+ excretion four- and twofold, respectively; hydrochlorothiazide co-treatment attenuated (P < 0.05) Ca2+ excretion in controls and during ALDOST without affecting augmented Mg2+ excretion whereas hdrochlorothiazide + spironolactone normalized Ca2+ and reduced Mg2+ excretion (P < 0.05). Compared with controls, plasma [Ca2+](o) at 4 weeks of ALDOST was reduced (0.89 +/- 0.02 versus 0.83 +/- 0.03 mmol/L; P < 0.05) but remained no different from levels in controls with hydrochlorothiazide and hydrochlorothiazide + spironolactone (0.88 +/- 0.04 and 0.97 +/- 0.03 mmol/L, respectively). Plasma [Mg2+](o) fell (P < 0.05) with ALDOST + hydrochlorothiazide (0.3 +/- 0.01 versus 0.34 +/- 0.01 mmol/L) and was prevented with spironolactone co-treatment (0.33 +/- 0.01 mmol/dL). Hypokalemia (2.9 +/- 0.2 mmol/L) occurred in rats with ALDOST + hydrochlorothiazide but not with spironolactone co-treatment. At 4 weeks of ALDOST, plasma parathyroid hormone was increased (30 +/- 4 versus 11 +/- 3 pg/mL; P < 0.05) and bone mineral density was reduced (0.153 +/- 0.006 versus 0.170 +/- 0.002 g/cm(2); P < 0.05). Co-treatments with either hydrochlorothiazide or hydrochlorothiazide + spironolactone each prevented bone loss. Conclusions: Hypercalciuria and hypermagnesuria accompany aldosteronism and account for a decline in their plasma ionized concentrations and secondary hyperparathyroidism with bone resorption. Attenuation of bone loss in aldosteronism can be achieved with hydrochlorothiazide; however, mono- and divalent cation homeostasis, together with bone integrity, are each preserved with the combination hydrochlorothiazide + spironolactone.
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