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Macrophages and bisphosphonate-related osteonecrosis of the jaw (BRONJ): evidence of local immunosuppression of macrophages in contrast to other infectious jaw diseases

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Abstract

Objectives

Bisphosphonates (BIP) are well established in bone diseases. A serious side effect is the bisphosphonate-related osteonecrosis of the jaw (BRONJ). Among different aetiology factors, local suppression of immune functions is gaining interest. The aim of this study was to analyze the function of macrophages in BRONJ in contrast to patients with osteoradionecrosis (ORN) and secondary chronic osteomyelitis (OM) of the jaws. Samples were also taken from patients with bisphosphonate medication (BP) without signs of infection, radiation therapy (RA), and osteoporosis (OP) as controls.

Material and methods

One hundred five patients with surgery to the jaw were included in this study: 33 patients with BRONJ, 17 with ORN, 11 with secondary chronic OM, 8 with RA, 25 with BP medication and 11 with OP. Samples were histologically analysed and monocytes/macrophages stained using CD14 and CD68. The number of positively marked cells was counted per view (pv), and the CD68/CD14 ratio was calculated. Statistically, the Naïve-Bayes and decision-tree classifier were used.

Results

The number of CD14 positive cells was 10.3 cells/pv in the BRONJ-group in as compared to 5 in the ORN- and 3.8 in the OM-group respectively. The number of CD68 positive cells was 11.4/pv (BRONJ-group) as compared to 14/pv (ORN-group) and 12.7/pv (OM-group). With 0.89, the BRONJ-group showed a statistically different CD68/CD14 ratio than ORN-group with 3.39 and OM-group with 3.03.

Conclusions

Our results indicate a different expression of CD14 and CD68 markers of monocytes/macrophages in BRONJ as compared to other jaw infections. This could be a sign of macrophage immunosuppression by BPs. In contrast, patients receiving BP medication without BRONJ showed no differences to other controls.

Clinical relevance

This is the first study that clinically indicates a compromised macrophage function at BRONJ sites in contrast to ORN or secondary OM sites. The BRONJ itself could be forwarded by this effect.

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Acknowledgments

We would like to thank the Konrad-Morgenroth-Foerderergesellschaft e. V., Muenster, Germany, for their financial support of this study.

We would also like to thank Mrs. Griffiths proofreading the manuscript and for her critical remarks.

We authors declare no other financial relationships with the organisation that sponsored the research, other organisations, nor other conflicts of interest.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany

    Sebastian Hoefert

  2. Department of Oral and Maxillofacial Surgery, Regional Plastic Surgery, Klinikum Vest, Knappschaftskrankenhaus, Academic Teaching Hospital, Ruhr-University Bochum, Recklinghausen, Germany

    Sebastian Hoefert & Harald Eufinger

  3. Institute of Pathology, Ruhr-University Bochum, Bochum, Germany

    Inge Schmitz

  4. Department of Informatics VII, Technical University of Dortmund, Dortmund, Germany

    Frank Weichert & Marcel Gaspar

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Correspondence to Sebastian Hoefert.

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Hoefert, S., Schmitz, I., Weichert, F. et al. Macrophages and bisphosphonate-related osteonecrosis of the jaw (BRONJ): evidence of local immunosuppression of macrophages in contrast to other infectious jaw diseases. Clin Oral Invest 19, 497–508 (2015). https://doi.org/10.1007/s00784-014-1273-7

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  • DOI: https://doi.org/10.1007/s00784-014-1273-7

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