RESUMEN
UNLABELLED: The goal of this study was to document how treatment with high doses of zoledronic acid affects dental extraction healing. Our results, showing significantly compromised osseous healing within the socket as well as presence of exposed bone and development of a sequestrum in one animal, provide a building block toward understanding osteonecrosis of the jaw. PURPOSE: The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction. METHODS: Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the fourth premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using microcomputed tomography (micro-CT) and dynamic histomorphometry. RESULTS: The initial infilling of the extraction socket with bone was not affected by ZOL, but subsequent removal of this bone was significantly suppressed compared to CON. After 8 weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of â¼50% per year in CON animals while ZOL-treated animals had a rate of <1% per year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw. CONCLUSIONS: These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw.
Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Imidazoles/efectos adversos , Enfermedades Maxilomandibulares/inducido químicamente , Osteonecrosis/inducido químicamente , Animales , Estudios de Casos y Controles , Perros , Femenino , Enfermedades Maxilomandibulares/diagnóstico por imagen , Osteonecrosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Extracción Dental , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos , Ácido ZoledrónicoRESUMEN
OBJECTIVE: The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. The aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. MATERIAL AND METHODS: Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to patients with cancer on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur was performed. RESULTS: Vehicle-treated OVX animals had significantly higher (eightfold) intracortical remodeling of the alveolar portion of the mandible compared to sham--this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate was lower with ZOL treatment compared to the corresponding VEH group. CONCLUSIONS: Under normal conditions, the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice it can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Difosfonatos/farmacología , Mandíbula/efectos de los fármacos , Ovariectomía , Proceso Alveolar/efectos de los fármacos , Proceso Alveolar/patología , Animales , Conservadores de la Densidad Ósea/administración & dosificación , Matriz Ósea/efectos de los fármacos , Matriz Ósea/patología , Calcificación Fisiológica/efectos de los fármacos , Colorantes , Dentina/efectos de los fármacos , Dentina/patología , Difosfonatos/administración & dosificación , Femenino , Fémur/efectos de los fármacos , Fémur/patología , Fluoresceínas , Colorantes Fluorescentes , Osteón/efectos de los fármacos , Osteón/patología , Imidazoles/administración & dosificación , Imidazoles/farmacología , Mandíbula/patología , Ratones , Ratones Endogámicos C3H , Necrosis , Osteogénesis/efectos de los fármacos , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/patología , Vehículos Farmacéuticos , Colorantes de Rosanilina , Calcificación de Dientes/efectos de los fármacos , Ácido ZoledrónicoAsunto(s)
Biotecnología/métodos , Distribución en Contracorriente/métodos , Proteínas/aislamiento & purificación , Brevibacterium/enzimología , Distribución en Contracorriente/instrumentación , Emulsiones , Escherichia coli/enzimología , Fumarato Hidratasa/aislamiento & purificación , Antígenos de Superficie de la Hepatitis B/aislamiento & purificación , Micelas , Modelos Químicos , beta-Galactosidasa/aislamiento & purificaciónRESUMEN
The N-glycans of purified recombinant middle surface protein (preS2+S) from hepatitis B virus, a candidate vaccine antigen expressed in a mnn9 mutant strain of Saccharomyces cerevisiae, have been characterized structurally. The glycans were released by N-glycanase treatment, isolated by size-exclusion chromatography on Sephadex G-50 and Bio-Gel P-4 columns, and analyzed by 500-MHz 1H NMR spectroscopy and fast atom bombardment mass spectrometry. The mixture of oligosaccharides was fractionated by HPLC, the major subfractions were isolated, and their carbohydrate compositions were determined by high-pH anion-exchange chromatography with pulsed amperometric detection. The combined results suggest that high-mannose oligosaccharides account for all the N-glycans released from preS2+S: structures include Man7GlcNAc2, Man8GlcNAc2, and Man9GlcNAc2 isomers in the ratios of 3:6:1. Approximately 80% of the oligosaccharides contain the C2,C6-branched trimannosyl structural element typical of yeast high-mannose oligosaccharides but not usually found in high-mannose oligosaccharides in animal glycoproteins.