Diphosphonates and phosphate homoeostasis in man.

1. The effects of three intravenous diphosphonates (etidronate, clodronate and aminohexane diphosphonate) on phosphate homoeostasis were studied in 30 patients with Paget's disease of bone and in three patients with hypoparathyroidism. 2. In Paget's disease, all three diphosphonates induced significant increases in serum phosphate and renal tubular reabsorption of phosphate. This effect was most marked and persistent after etidronate, whereas in the clodronate- and aminohexane diphosphonate-treated patients the increases were less, of shorter duration and followed thereafter by significant decreases in serum phosphate and renal tubular reabsorption of phosphate. Unlike etidronate, both clodronate and aminohexane diphosphonate caused a significant reduction in serum and urinary calcium, with appropriate homoeostatic increases in immunoassayable parathyroid hormone. 3. Phosphaturic responses to infused parathyroid hormone were observed in two patients with etidronate-induced hyperphosphataemia. 4. In three hypoparathyroid patients, clodronate induced a more marked increase in serum phosphate and renal tubular reabsorption of phosphate than in Paget's disease, which was of comparable degree but of shorter duration than that after etidronate in Paget's disease. 5. These findings suggest that all three diphosphonates increase renal tubular reabsorption of phosphate, but that this effect is attenuated with those diphosphonates which induce secondary hyperparathyroidism.