The hyperphosphatemic effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP^TM): Renal handling of phosphorus and the renal response to parathyroid hormone

To determine the mechanism responsible for serum phosphorus elevation during therapy with disodium etidronate (ethane-1-hydroxy-1,1-diphosphonate, EHDP^TM), 30 mg. per kilogram EHDP^TM was administered daily, orally, in 4 divided doses to 10 adult male volunteers age 22 to 45 for 11 or 12 days. Clearances of calcium, phosphorus, and creatinine were estimated in each of 4 one hour periods on 2 different days before, and on 2 days at the end of therapy while still on the drug. Intravenous bovine parathyroid hormone (PTH) was given at the beginning of the experiment on the second day in each case. Diffusible calcium and phosphorus clearances were determined on 5 of these subjects. The response to 40 units (5 subjec or 200 units (5 subjects) bovine PTH during treatment with EHDP^TM30 mg. per kilogram for 11 or 12 days was compared to the response during the control period without treatment. Urine cyclic AMP excretion was also compared in each case. EHDP^TM caused a significant rise in total and diffusible serum phosphorus levels with nonsignificant differences between them. Phosphorus clearance was decreased (P <0.01) but basal phosphorous excretion was unchanged by EHDP^TM therapy. The phosphaturia and urine cyclic AMP excretion in response to intravenous bovine PTH, 40 units (5 subjects) or 200 units (5 subjects) was unaltered by EHDP^TM therapy. The per cent change in phosphorus clearance in response to intravenous bovine PTH was also unaltered by treatment with EHDP^TM. Urine calcium excretion was decreased for 2 hours following bovine PTH injection, both with and without treatment with EHDP^TM. The phosphaturic response to 200 units bovine PTH was slightly greater than the response to 40 units, however, the urinary cyclic AMP excretion in response to 200 units bovine PTH was about ten-fold higher than the response to 40 units. It was concluded that EHDP^TM causes hyperphosphatemia by increasing tubular reabsorption of phosphorus without causing inhibition of parathyroid hormone action on renal tubules. It is assumed that a mechanism (s) other than PTH exists for control of renal handling of phosphorus and that EHDP^TM affects it (them).