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Use of pamidronate disodium to reduce cholecalciferol-induced toxicosis in dogs

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  • 1 Department of Pathology, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.
  • | 2 Department of Pathology, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.
  • | 3 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.
  • | 4 Departments of Pharmacology and Toxicology, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.
  • | 5 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.
  • | 6 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.
  • | 7 Department of Pathology, College of Veterinary Medicine, Michigan State University, Lansing, MI 48909.

Abstract

Objective—To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner.

Animals—20 clinically normal, 8- to 12-month-old male Beagles.

Procedure—All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed.

Results—One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium × phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules.

Conclusions and Clinical Relevance—Pamidronate disodium is a potentially useful drug to reduce CCFinduced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs. (Am J Vet Res 2000;61:9–13)

Abstract

Objective—To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner.

Animals—20 clinically normal, 8- to 12-month-old male Beagles.

Procedure—All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed.

Results—One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium × phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules.

Conclusions and Clinical Relevance—Pamidronate disodium is a potentially useful drug to reduce CCFinduced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs. (Am J Vet Res 2000;61:9–13)