Abstract
Bisphosphonate-associated osteonecrosis (BON) is a complication that almost exclusively affects the jaw bones. The clinical presentation of BON often mimics that of other conditions, such as routine dental disease, osteoradionecrosis or avascular necrosis; therefore, diagnosis can be difficult. As this complication has only been recognized within the past 10 years, management strategies for patients with BON are poorly defined. Physicians must choose between continuing the bisphosphonate therapy (to reduce the risk of skeletal complications in patients with metastatic bone disease or osteoporosis) and discontinuing the drug (to possibly improve the odds for tissue healing). A conservative or aggressive management strategy must be chosen with limited evidence that the outcome of either strategy will be successful. BON is most prevalent in patients with cancer using intravenous nitrogen-containing bisphosphonates. The pathobiology of this complication is not fully understood and the diagnosis relies on the clinical manifestations of the condition. Future research should focus on the pathobiological mechanisms involved in the development of BON, which could help explain why this complication affects only a small number of those who use bisphosphonates, and also suggest strategies for prevention and management.
Key Points
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Higher levels of evidence than those currently available are needed to help establish the natural history, true prevalence, prevention and treatment strategies and prognosis for bisphosphonate-associated osteonecrosis (BON)
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Most studies of BON are case series, which are susceptible to bias as they lack a comparator group
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Prospective studies with well-documented follow-up of patients and participation of a dental expert seem to yield higher prevalence rates than other study designs, such as retrospective studies
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Diagnosis of BON requires exposed necrotic bone that does not respond to conventional therapy for osteonecrosis in a patient receiving bisphosphonates with no history of head and neck irradiation
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Patients with BON refractory to conservative local debridement and use of topical and systemic antibiotics might respond positively to more aggressive surgical flaps and bone resection
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The assessment of healing after patients have been treated for BON is not well defined; evidence of healing should comprise improvements in symptoms, mucosal healing and radiographic parameters
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All authors contributed equally to researching the data, discussing the content, reviewing and editing the manuscript before submission. C. A. Migliorati, J. B. Epstein and J. R. Berenson contributed equally to writing the article. The image in Figure 1 was supplied by C. A. Migliorati.
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C. A. Migliorati has been a consultant for Amgen. J. R. Berenson has been a speaker and consultant and received research grants from Celgene, Cephalon, Novartis and Millennium, and has been a speaker and consultant for OrthoBiotech. He has received research grants and been a consultant for Amgen, CuraGen, Cytogen and Seattle Genetics, and has received research grants from Pfizer and Ziopharm. The other authors declare no competing interests.
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Migliorati, C., Epstein, J., Abt, E. et al. Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review. Nat Rev Endocrinol 7, 34–42 (2011). https://doi.org/10.1038/nrendo.2010.195
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DOI: https://doi.org/10.1038/nrendo.2010.195
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