title: A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw.
abstract: The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach.
authors.affiliation: Department of Dental Science, University of Trieste, Trieste, Italy. m.biasotto@fmc.units.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Biasotto
authors.forename: Silvia
authors.initials: S
authors.lastname: Chiandussi
authors.forename: Serena
authors.initials: S
authors.lastname: Zacchigna
authors.forename: Silvia
authors.initials: S
authors.lastname: Moimas
authors.forename: Franca
authors.initials: F
authors.lastname: Dore
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pozzato
authors.forename: Fabio
authors.initials: F
authors.lastname: Cavalli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Zanconati
authors.forename: Luca
authors.initials: L
authors.lastname: Contardo
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Lenarda
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007275:Injections, Intravenous; D007571:Jaw Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008439:Maxillary Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology; D010020:Osteonecrosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D014081:Tooth Extraction / Q000009:adverse effects; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid