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Bisphosphonates and osteomyelitis of the jaw: a pathogenic puzzle

Nature Clinical Practice Oncology volume 4, pages 711–721 (2007)Cite this article

Abstract

The maxillary and mandibular bones undergo high-turnover remodeling to maintain mechanical competence. Common dental or periodontal diseases can increase local bone turnover. Bisphosphonates (BPs) accumulate almost exclusively in skeletal sites that have active bone remodeling. The maxillary and mandibular bones are preferential sites for accumulation of BPs, which become buried under new layers of bone and remain biologically inactive for a long time. Surgical odontostomatological procedures create open bony wounds that heal quickly and without infection, as a result of activation of osteoclasts and subsequently osteoblasts. Once BPs are removed from the bone via activation of osteoclasts after a tooth extraction or a periodontal procedure, they induce osteoclast apoptosis. This inhibition of osteoclast bone resorption impairs bone wound healing because of decreased production of cytokines derived from the bone matrix, and the bone is exposed to the risk of osteomyelitis and necrosis. The pathogenic relationship between BPs and osteonecrosis of the jaw is unclear, but there is evidence to indicate an association between high-dose BP treatment and exposure to dental infections or oral surgical procedures. A better knowledge of the interactions between BPs and jaw and maxillary bone biology will improve clinical and therapeutic approaches.

Key Points

  • Osteonecrosis of the jaw or maxillary bone associated with bisphosphonate (BP) treatment is a relatively rare but severe clinical condition; however, a clear pathogenic relationship between osteonecrosis of the jaw and BPs has not been established

  • The jaw and the maxillary bone are characterized by high bone turnover that is constantly stimulated by mechanical stress, tooth movements or loss, periodontitis, and odontostomatological procedures, which are particularly frequent in cancer patients

  • Treatment with an amino-BP over long time periods causes the drug to accumulate in an inactive state within the alveolar bone

  • Physical trauma or infection activates local bone remodeling, releasing pharmacological doses of BPs that inhibit the osteoclast-driven bone healing

  • The nonhealing wound exposes the alveolar bone to the risk of infection by commensal flora and the wound can progress to necrotic osteomyelitis; there is no convincing evidence that a direct necrotic effect is mediated through inhibition of angiogenesis

  • The possibility of accumulation of substantial doses of BPs at skeletal sites other than those affected by bone metastases could have implications for the optimization of BP schedules to improve response in patients

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Figure 1: Mechanism of bisphosphonate accumulation in the jaw and a hypothetical pathogenic role in osteonecrosis.
Figure 2: Schematic representation of the interaction between periodontitis, bisphosphonates and alveolar bone.

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Authors and Affiliations

  1. F Bertoldo is Assistant Professor of Internal Medicine and Chief of the Bone Mineral Metabolism Unit and V Lo Cascio is Professor of Internal Medicine and Chief of the Department of Biomedical and Surgical Sciences, University of Verona, Verona,

    Francesco Bertoldo & Vincenzo Lo Cascio

  2. D Santini is Assistant Professor in Immunology at the Department of Medical Oncology, University of Campus Bio-Medico, Rome, Italy.,

    Daniele Santini

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Correspondence to Daniele Santini.

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Bertoldo, F., Santini, D. & Lo Cascio, V. Bisphosphonates and osteomyelitis of the jaw: a pathogenic puzzle. Nat Rev Clin Oncol 4, 711–721 (2007). https://doi.org/10.1038/ncponc1000

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