The bone biologic effects of zoledronate in healthy dogs and dogs with malignant osteolysis.
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.


OBJECTIVE
IV-administered zoledronate will reduce homeostatic bone turnover in healthy dogs and pathologic bone resorption in dogs diagnosed with primary and secondary bone tumors.


METHODS
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 (> or =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
In dogs with skeletal neoplasms, IV-administered zoledronate exerts bone biologic effects, appears safe, and can provide pain relief.
Fan
T M
TM
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802-4714, USA. t-fan@uiuc.edu
de Lorimier
L P
LP
Garrett
L D
LD
Lacoste
H I
HI
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects*; D015331:Cohort Studies; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy* / Q000209:etiology; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000662:veterinary; D010014:Osteolysis / Q000188:drug therapy / Q000209:etiology / Q000662:veterinary*; D011446:Prospective Studies; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid