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Compromised osseous healing of dental extraction sites in zoledronic acid-treated dogs

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Abstract

Summary

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 ∼50% 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.

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Acknowledgments

We would like to thank the following individuals who contributed to this work: Binal Pandya for the assistance with the histological analyses, Mark Koivuniemi for the CT scanning/analysis and the histological sectioning, Nichole Leahy for the histological sectioning, Keith Condon for the histological preparation, and Carrie Pell and her staff for the assistance with animal care. This work was supported by grants from the Showalter Foundation and the NIH (R21-DE019686 and S10-RR023710).

Conflicts of interest

Dr. Allen and Dr. Burr receive research support and are consultants for Procter & Gamble Pharmaceuticals. Dr. Burr serves as a consultant for Amgen.

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, 635 Barnhill Drive, MS-5035, Indianapolis, IN, 46202, USA

    M. R. Allen, D. J. Kubek & D. B. Burr

  2. Department of Orthopedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    D. B. Burr

  3. Department of Biomedical Engineering Program, Indiana University–Purdue University Indianapolis, Indianapolis, IN, USA

    D. B. Burr & T.-M. G. Chu

  4. Department of Restorative Dentistry, Indiana University School of Dentistry, Indianapolis, IN, USA

    T.-M. G. Chu

  5. New York Center for Orthognathic and Maxillary Surgery, Lake Success, NY, USA

    S. L. Ruggiero

  6. Department of Oral and Maxillofacial Surgery, School of Dental Medicine, SUNY at Stony Brook, Stony Brook, NY, USA

    S. L. Ruggiero

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  1. M. R. Allen
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  2. D. J. Kubek
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  4. S. L. Ruggiero
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  5. T.-M. G. Chu
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Correspondence to M. R. Allen.

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Allen, M.R., Kubek, D.J., Burr, D.B. et al. Compromised osseous healing of dental extraction sites in zoledronic acid-treated dogs. Osteoporos Int 22, 693–702 (2011). https://doi.org/10.1007/s00198-010-1268-4

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  • DOI: https://doi.org/10.1007/s00198-010-1268-4

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