title: Bacterial profile and bone healing in rats receiving cancer therapeutic doses of bisphosphonates and corticosteroids: a pilot study.
abstract: The microbial aetiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains undefined. This study investigated the oral microbiota and socket healing after zoledronic acid (ZA) and dexamethasone (DX) administration. Fourteen rats assigned randomly to experimental (n=8) and control (n=6) groups were injected with ZA+DX or saline, respectively, for 3 weeks prior to and 9 weeks after the extraction of left first upper and lower molars. Whole genomic DNA probes of 38 bacterial species and five Candida species were hybridized to DNA extracted from biofilm samples on exposed bone and adjacent teeth. Only experimental rats exhibited exposed bone at euthanasia. All BRONJ-like lesions were colonized by Staphylococcus pasteuri, Streptococcus parasanguinis, and Streptococcus mitis. A significant correlation was observed between the mean proportions of species colonizing BRONJ-like lesions and the teeth of experimental rats (r=0.818, P<0.001). Significant differences were seen in several species colonizing the teeth of control rats compared to experimental rats (P<0.05). Micro-computed tomography analyses revealed higher residual bone in mandibular (P=0.001) and maxillary (P=0.108) tooth sockets of experimental rats. BRONJ-like lesions were colonized mainly by non-pathogenic bacteria. ZA+DX administered to rats at doses equivalent to those given to cancer patients resulted in changes to the oral biofilm and impaired bone healing following tooth extraction.
authors.affiliation: Division of Restorative Dentistry, Faculty of Dentistry, McGill University, Montreal, QC, Canada; Bone Engineering Labs, Research Institute, McGill University Health Center, Montreal, QC, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Jabbour
authors.affiliation: Department of Dental Materials and Prosthodontics, Faculty of Dentistry of Ribeirão Preto, University of Sao Paulo, Brazil. Electronic address: cassionasc@forp.usp.br.
authors.forename: C
authors.initials: C
authors.lastname: do Nascimento
authors.affiliation: Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, McGill University, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: El-Hakim
authors.affiliation: Bone Engineering Labs, Research Institute, McGill University Health Center, Montreal, QC, Canada; Department of Medicine and Surgery, Faculty of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: J E
authors.initials: JE
authors.lastname: Henderson
authors.affiliation: Division of Restorative Dentistry, Faculty of Dentistry, McGill University, Montreal, QC, Canada; Department of Dental Materials and Prosthodontics, Faculty of Dentistry of Ribeirão Preto, University of Sao Paulo, Brazil.
authors.forename: R F
authors.initials: RF
authors.lastname: de Albuquerque Junior
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000818:Animals; D018441:Biofilms; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000188:drug therapy* / Q000382:microbiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002175:Candida / Q000302:isolation & purification; D003907:Dexamethasone / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D010865:Pilot Projects; D011897:Random Allocation; D051381:Rats; D013210:Staphylococcus / Q000302:isolation & purification; D013291:Streptococcus / Q000302:isolation & purification; D034361:Streptococcus mitis / Q000302:isolation & purification; D014081:Tooth Extraction; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D000305:Adrenal Cortex Hormones; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D003907:Dexamethasone
keywords: DNA checkerboard; bisphosphonates; bone repair; oral biofilm; tooth extraction