Bone loss in rats with aldosteronism.

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 Ca and Mg excretion; plasma ionized [Ca]o and [Mg]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 mug/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 Ca and Mg excretion four- and twofold, respectively; hydrochlorothiazide co-treatment attenuated (P<0.05) Ca excretion in controls and during ALDOST without affecting augmented Mg excretion whereas hydrochlorothiazide+spironolactone normalized Ca and reduced Mg excretion (P<0.05). Compared with controls, plasma [Ca]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 [Mg]o fell (P<0.05) with ALDOST+hydrochlorothiazide (0.23+/-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; 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.