Regulation of calcium-parathyroid hormone feedback in primary hyperparathyroidism: effects of bisphosphonate treatment

Dichloromethylene bisphosphonate (C12MBP), a powerful inhibitor of bone resorption, was administered to 27 patients with primary hyperparathyroidism. It was given by either intravenous infusion (six patients, 500-100 mg day), or by intramuscular injection (six patients, 100-200 mg/day) or by mouth (15 patients, 1600-2400 mg/day) for 20-180 days. Sustained suppression of bone resorption was observed in all patients, as judged by a fall in the urinary hydroxyproline excretion. In contrast, the hypocalcaemic effect was inconsistent and short-lived, particularly in the patients without overt bone disease. The fall in serum calcium seemed largely to be due to a transient dissociation between bone resorption and bone formation and was associated with increases in circulating parathyroid hormone (PTH). In ten patients given the bisphosphonate orally for 6 months, serum calcium was unchanged but serum PTH was significantly raised. These results suggest that C12MBP may be of use for short-term correction of severe hypercalcaemia due to hyperparathyroidism, particularly in the patients with overt bone disease. However, its long-term use should not be recommended because of increased PTH secretion.