Bisphosphonate use and osteonecrosis of the jaw: Pharmacovigilance and reporting of this serious adverse event from the Research on Adverse Drug Events and Reports (RADAR) project

6519 Background: Two years after zoledronate, received FDA approval, four dental professionals treated 107 cases of osteonecrosis of the jaw (ONJ). We review the timeline and source for initial recognition of ONJ and the comprehensiveness of dissemination of information on this adverse drug event. Methods: Data sources included primary case series from dental professionals; published case reports, clinical trials, and cases reported to the manufacturers or the FDA. Exposure adjusted incidence rates estimates were derived from manufacturer sponsored and investigator initiated review of claims data from large cancer centers. Safety notifications were disseminated by the manufacturers, regulatory authorities, and academic investigators. Results: Between 2001 and 2003, 107 patients with ONJ received care from dental professionals. In late 2003, and 2004 peer-reviewed case series were published. By 2006, safety databases maintained by the FDA, the manufacturer, and the RADAR project included information on 2,270, 1,178, and 368 cases of ONJ, respectively. In 2004 and 2005, incidence estimates of 0.8 and 22 ONJ cases per 1,000 person-years of intravenous bisphosphonate therapy were reported by the manufacturer and academic investigators. From 2003 to 2006, safety information from manufacturers, national regulatory authorities, case series, and clinical guidelines were disseminated. Conclusions: Recognition and reporting of ONJ occurred two years after FDA approval of zoledronate, dissemination of safety information occurred in the third year, and publications were disseminated from year three to year five. The life-cycle for identification and information dissemination for this serious adverse drug reaction was short and comprehensive. [Table: see text] [Table: see text]