To identify potential risk factors for the development of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates, we conducted a MEDLINE search. We identified 44 English-language published case reports and case series describing 481 patients with bisphosphonate-related ONJ. Our review of these reports indicated that ONJ occurs more frequently in patients receiving intravenous bisphosphonates (453 patients [94.2%]) than in patients receiving oral bisphosphonates (28 patients [5.8%]). Most patients who developed ONJ had cancer (451 patients [93.8%]), with multiple myeloma being the most common diagnosis, followed by breast, prostate, and lung cancers. Nearly one third of patients had a history of glucocorticoid use. The inciting event (reported in 449 patients) preceding the diagnosis of ONJ was a tooth extraction or other surgical or invasive dental procedure in 309 patients (68.8%), whereas 93 patients (20.7%) developed ONJ spontaneously. Guidelines for the prevention and treatment of bisphosphonate-associated ONJ have been developed but are largely based on anecdotal evidence. Patients receiving bisphosphonates must be counseled on the risks and benefits of therapy. Further studies will help to elucidate the pathophysiology, frequency, and risk factors for development of bisphosphonate-associated ONJ.
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