Short term zoledronic acid induces necrotic foci in dog jaws

Bisphosphonates (BP) therapy with drugs such as Fosamax and Zometa has been associated with osteonecrosis of the jaws. However, experimental evidence has not demonstrated the direct relationship between osteonecrosis of the jaws (ONJ) and BP therapy. Objectives: The goal of this study was to examine the effect of a short duration (4 months) of zoledronic acid (ZA) administration on skeletal sites in a dog model. We hypothesized that there would be no difference in the control and experimental groups in the amount of necrosis in the jaws. Methods: Four aged (2-3 yrs) dogs were administered (0.1 mg/kg) ZA for 4 months, while 2 age matched control dogs received no drug. At sacrifice, ninety-seven fresh bone sections (57 mandible, 27 maxilla, 7 rib and 6 femur) were obtained and processed immediately for the lactate dehydrogenase assay. The slides were blinded and necrosis was identified by lack of dark blue formazan granules in the osteocytes. The area of necrosis and total bone area was measured using Olympus BX51 microscope (MicroSuite Special Edition software). Descriptive statistics were obtained. Results: No eroded oral lesions of ONJ were seen in the dogs. However, there was nearly a 4 fold greater amount of % necrosis (Mean, SD) in the ZA (0.6, 1.3) than in the control (0.14, 0.38) groups. The % necrosis (Mean, SD) in each of the skeletal sites was as follows: mandible (0.39, 0.88); maxilla (1.17, 2.04), rib (0.50, 0.49) and femur (0.19, 0.07). We have developed an animal model that demonstrates initial histologic foci of necrosis after ZA administration. Limitations of this study include a small sample size and short duration of drug administration. Conclusion: Short duration of ZA administration induces necrotic foci in the jaws; however no eroded intraoral lesions developed.