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Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw

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Abstract

Objectives

The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model.

Materials and methods

Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison.

Results

Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30–80 μm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05).

Conclusion

Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ.

Clinical Relevance

Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

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Authors and Affiliations

  1. Graduate School of Clinical Implant Dentistry, Ewha Womans University, Seoul, South Korea

    Jin-Woo Kim, Maria Erika A. Landayan, Ju-Young Lee, Jacquiline Czar I. Tatad, Sun-Jong Kim & Myung-Rae Kim

  2. Research Institute for Intractable Osteonecrosis of the Jaw, School of Medicine, Ewha Womans University, Seoul, South Korea

    Jin-Woo Kim, Maria Erika A. Landayan, Ju-Young Lee, Jacquiline Czar I. Tatad, Sun-Jong Kim & Myung-Rae Kim

  3. Department of Oral and Maxillofacial Surgery, Yonsei University, Seoul, South Korea

    In-Ho Cha

  4. Department of Oral & Maxillofacial Surgery, Ewha Womans University Medical Center, Anyangcheon-ro 1071, Yangcheon-gu, Seoul, 158-710, South Korea

    Jin-Woo Kim, Ju-Young Lee & Sun-Jong Kim

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  1. Jin-Woo Kim
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Correspondence to Sun-Jong Kim.

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Ethical approval

All applicable institutional guidelines for the care and use of animals were followed.

Conflict of interest

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Funding

This study was supported by the Ewha Global Top5 Grant 2013 (1–2013-0469-001-1) of the Ewha Womans University, Seoul, Korea.

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Additional information

This article was based on the dissertation of Maria Erika A. Landayan from Ewha Womans University, Graduate School of Clinical Dentistry.

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Kim, JW., Landayan, M., Lee, JY. et al. Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw. Clin Oral Invest 20, 2251–2258 (2016). https://doi.org/10.1007/s00784-016-1718-2

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  • DOI: https://doi.org/10.1007/s00784-016-1718-2

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