Bacterial profile and bone healing in rats receiving cancer therapeutic doses of bisphosphonates and corticosteroids: a pilot study

doi:10.1016/j.ijom.2015.12.017

International Journal of Oral and Maxillofacial Surgery

Volume 45, Issue 9, September 2016, Pages 1162-1169

https://doi.org/10.1016/j.ijom.2015.12.017 Get rights and content

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.

Section snippets

Rats with BRONJ-like disease

The Animal Use Protocol was approved by the necessary authorities. A total of 14 retired breeder female Sprague-Dawley rats (4–6 months old) were divided randomly into control (n = 6) and experimental (n = 8) groups. Control rats received no medication and experimental rats received zoledronic acid (ZA; 125 μg/kg twice a week) and dexamethasone (DX; 5 mg/kg once a week) for a total of 12 weeks. In a previous work by the present investigators, rats exposed to this drug combination consistently

Microbiological results

Of the 43 different microbial species investigated, a total of 39 were detected on the exposed bone and 26 on the adjacent teeth of the experimental rats treated with ZA+DX, and 40 were detected on the teeth of control rats that received no treatment. Staphylococcus pasteuri, Streptococcus parasanguinis, Streptococcus mitis, Streptococcus gordonii, and Streptococcus oralis species had the highest mean proportions. S. pasteuri, S. parasanguinis, and S. mitis were detected on all exposed bone in

Discussion

The combined administration of ZA+DX associated with trauma to the jaw bone, caused by tooth extraction, resulted in exposed bone resembling BRONJ in all experimental rats. A DNA checkerboard technique using 43 genomic DNA probes prepared from human oral bacteria and fungi relevant to human health was employed to detect changes in the bacterial species colonizing the teeth of the ZA+DX rats. A similarity in bacterial profile of the exposed bone and teeth was also noted, and no loss of alveolar

Funding

Zaher Jabbour has received awards from the Fonds de Recherche en Santé du Québec (FRSQ), the FRSQ-Réseau de Recherche en Santé Buccodentaire et Osseuse (RSBO), and the Fondation de l’Ordre des Dentistes du Québec (FODQ). The study was made possible through operating funds from FODQ and Synthes Canada, and infrastructure support from the FRQ-S-RSBO and the Jo Miller Orthopaedic Research Fund.

Competing interests

None.

Ethical approval

The Animal Use Protocol was approved by the University Animal Care Committee to perform the current experiment according to the Principles of Laboratory Animal Care established by the Canadian Council on Animal Care (CCAC).

Patient consent

Not required.

Acknowledgements

The technical assistance provided by Ailian Li for the histological staining was greatly appreciated.

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Research PaperClinical PathologyBacterial profile and bone healing in rats receiving cancer therapeutic doses of bisphosphonates and corticosteroids: a pilot study