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Epidemiology and pathogenesis of osteonecrosis of the jaw

Nature Reviews Rheumatology volume 8, pages 90–96 (2012)Cite this article

Abstract

Osteonecrosis of the jaw (ONJ) is defined as exposed bone in the oral cavity that persists despite appropriate therapy. Over the past decade, ONJ has been reported in about 5% of patients with cancer receiving high-dose intravenous bisphosphonates, and more recently in similar patients treated with denosumab, another potent inhibitor of osteoclastic bone resorption. The condition has also been described in patients treated with bisphosphonates for benign diseases, such as osteoporosis, but whether bisphosphonates or denosumab increase the incidence above that seen in untreated patients of comparable age and frailty is yet to be established. The pathogenesis of ONJ is uncertain: the toxic effects of bisphosphonates in a wide variety of cells could increase susceptibility to infections in the oral cavity or impair mucosal healing, and denosumab might interfere with monocyte and macrophage function. Local osteolysis is an important defense against infection on bone surfaces that is blocked by both bisphosphonates and denosumab. Preventive dentistry prior to high-dose antiresorptive therapy is a critical measure in cancer patients, but is not usually justified in patients with osteoporosis. The management of established ONJ lesions is problematic: the greatest success seems to come from vigorous antimicrobial therapy with judicious use of surgical debridement.

Key Points

  • Osteonecrosis of the jaw (ONJ) is defined as the presence of exposed bone in the mouth that persists despite appropriate therapy

  • ONJ is primarily a problem encountered in patients with cancer receiving high-dose intravenous bisphosphonates for the prevention of skeletal-related events, of whom about 5% develop the condition

  • ONJ has now been reported at a similar frequency in patients with cancer treated with denosumab, a monoclonal antibody against RANKL

  • ONJ has also been reported in patients treated with bisphosphonates for osteoporosis, but it is not yet established whether bisphosphonates increase the incidence above that seen in untreated patients of comparable age and frailty

  • The pathogenesis of ONJ is uncertain, but local toxicity from bisphosphonates or blockade of the normal osteolytic response to infection on a bone surface might be important factors

  • Preventive dentistry prior to initiation of high-dose antiresorptive therapy is important in patients with cancer, but is not usually justified in patients with osteoporosis

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Figure 1: Gross and radiographic appearance of osteonecrosis of the jaw.
Figure 2: Tissue specimen from a patient with osteonecrosis of the jaw, demonstrating a bone resorption lacuna containing large, multinucleated osteoclasts (black arrows) and viable osteocytes (white arrows) in some areas of the bone.
Figure 3: Bacterial infection and biofilms on bone.
Figure 4: Growth inhibition in cells of soft-tissue origin cultured on a bone surface pretreated with zoledronate.
Figure 5

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Acknowledgements

This work was supported by the Health Research Council of New Zealand.

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  1. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand

    Ian R. Reid & Jillian Cornish

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Both authors researched data for the article and discussed its content. I. R. Reid wrote the article, and J. Cornish performed review/editing of the manuscript before submission.

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I. R. Reid has acted as a consultant for and received speakers bureau and grant/research support from Amgen and Novartis. He has also received speakers bureau and grant/research support from Merck. J. Cornish declares no competing interests.

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Reid, I., Cornish, J. Epidemiology and pathogenesis of osteonecrosis of the jaw. Nat Rev Rheumatol 8, 90–96 (2012). https://doi.org/10.1038/nrrheum.2011.181

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