This study was conducted at the Veterinary Teaching Hospital, University of Illinois, Urbana, IL. Findings have been presented in part at the 26th Annual Veterinary Cancer Society Conference, Pine Mountain, GA, 2006.
The Bone Biologic Effects of Zoledronate in Healthy Dogs and Dogs with Malignant Osteolysis
Article first published online: 10 MAR 2008
Copyright © 2008 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 22, Issue 2, pages 380–387, March–April 2008
How to Cite
Fan, T.M., De Lorimier, L.P., Garrett, L.D. and Lacoste, H.I. (2008), The Bone Biologic Effects of Zoledronate in Healthy Dogs and Dogs with Malignant Osteolysis. Journal of Veterinary Internal Medicine, 22: 380–387. doi: 10.1111/j.1939-1676.2008.0046.x
- Issue published online: 10 MAR 2008
- Article first published online: 10 MAR 2008
- Submitted July 17, 2007; Revised September 18, 2007; Accepted October 26, 2007.
- Dual-energy x-ray absorptiometry;
- Pain alleviation;
- Primary and secondary bone neoplasm;
- Urine N-telopeptide
Background: Malignant osteolysis is a process whereby cancer cells in concert with osteoclasts erode bone matrix. Aminobisphosphonates (NBPs) such as zoledronate induce osteoclast apoptosis and thereby decrease malignant skeletal destruction, severity of bone pain, and frequency of pathologic fracture.
Hypothesis: IV-administered zoledronate will reduce homeostatic bone turnover in healthy dogs and pathologic bone resorption in dogs diagnosed with primary and secondary bone tumors.
Animals: Six healthy dogs and 20 dogs with naturally occurring primary or metastatic bone tumors were administered zoledronate IV.
Methods: Prospective study: In all dogs, healthy (n = 6) and with malignant osteolysis (n = 20), the bone biologic effects of zoledronate were evaluated by quantifying changes in serum C-telopeptide (CTx) or urine N-telopeptide (NTx) concentrations or both. In dogs with osteosarcoma (OSA) (n = 10), serial changes in tumor relative bone mineral density (rBMD) assessed by dual-energy x-ray absorptiometry were used to characterize zoledronate's antiresorptive effects within the immediate tumor microenvironment. Additionally, the biochemical tolerability of zoledronate was assessed in 9 dogs receiving multiple (≥2) consecutive treatments.
Results: All dogs had significant reductions in serum CTx or urine NTx concentrations or both after zoledronate administration. In a subset of dogs with appendicular OSA, reduced urine NTx concentrations and increased primary tumor rBMD coincided with improved limb usage as reported by pet owners in dogs treated with zoledronate and concurrent oral analgesics. Multiple zoledronate infusions were not associated with biochemical evidence of toxicosis.
Conclusions and Clinical Importance: In dogs with skeletal neoplasms, IV-administered zoledronate exerts bone biologic effects, appears safe, and can provide pain relief.