Clodronate in the medical management of hyperparathyroidism.
The skeletal manifestations of hyperparathyroidism are due to the stimulation of osteoclast-mediated bone resorption by high circulating concentrations of parathyroid hormone (PTH). Since diphosphonates inhibit PTH-mediated bone resorption, we assessed the effects of clodronate in 42 patients with hypercalcaemia and increased bone resorption due to primary hyperparathyroidism (20 patients), secondary hyperparathyroidism in chronic renal failure (12 patients on haemodialysis replacement therapy) and tertiary hyperparathyroidism following successful renal transplantation (10 patients). Clodronate (0.8-1.6 g daily by mouth or 300 mg given as an intravenous infusion following five consecutive dialysis treatments) significantly decreased serum calcium and biochemical indices of bone resorption in the three groups studied. In primary and tertiary hyperparathyroidism, serum calcium values remained above the upper limit of the reference range despite suppression of bone resorption due to the unopposed effect of PTH on renal tubular reabsorption of calcium. Prolonged treatment (3 months) was associated with a partial recurrence of hypercalcaemia in 8 of 12 patients with primary hyperparathyroidism despite continued effects on bone resorption, possibly due to a secondary decrease in bone formation. These studies indicate that clodronate is capable of suppressing PTH-mediated bone resorption in disorders of parathyroid secretion and may prove to be a useful adjunct in their medical management.
D000284:Administration, Oral; D001862:Bone Resorption / Q000187:drug effects*; D004002:Clodronic Acid / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D006934:Hypercalcemia / Q000188:drug therapy*; D006961:Hyperparathyroidism / Q000150:complications* / Q000188:drug therapy; D006962:Hyperparathyroidism, Secondary / Q000150:complications; D007262:Infusions, Intravenous
D004164:Diphosphonates; D004002:Clodronic Acid; D006909:Hydroxyproline