It has been shown that bone mineralization probably increases in individuals receiving long-term thiazide therapy. Patients who have underlying disorders of calcium metabolism, such as primary hyperparathyroidism, or who are being treated with vitamin D supplements may be at risk for hypercalcemia when receiving thiazide therapy. Serum calcium levels should be monitored for two months after initiating thiazide therapy. The hypocalciuric action of amiloride is probably achieved through secondary stimulation of a sodium-calcium antiporter at the epithelial cell basolateral membrane that leads to stimulation of calcium transport in the distal convoluted tubule. Amiloride may be particularly useful because it retards potassium excretion and prevents thiazide-induced hypokalemia.
Potassium depletion leads to intracellular acidosis and causes hypocitraturia.
Thiazide therapy is contraindicated or ineffective in approximately seven to 15 percent of patients treated. In such cases, amiloride can be used as an adjunct or substitute. Phosphates act by reducing bone resorption of calcium and promoting renal calcium reabsorption. Diarrhea is the most common short-term side effect and is a frequent problem. Because these agents must be administered four times a day, such therapy is somewhat inconvenient.