ACLASTA (ZOLEDRONIC ACID)

Zoledronic acid is effective as sole therapy for the management of hypercalcemia in dogs. All hypercalcemic dogs in this study had an initial decrease in ionized calcium. One dog that had successive treatments for hypercalcemia was well controlled with ZA alone.

Zoledronic acid (ZA) is a member of the bisphosphonate family of drugs, specifically classified as a nitrogen-containing bisphosphonate or aminobisphosphonate. Bisphosphonates are commonly used for the management of osteoporosis in humans. They are effective in the management of both bone pain (ostealgia) and hypercalcemia in dogs.

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.

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 (> 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 and clinical importance: In dogs with skeletal neoplasms, IV-administered zoledronate exerts bone biologic effects, appears safe, and can provide pain relief.