Background Bisphosphonate-related osteonecrosis of the jaw (BRONJ) adverse drug reactions (ADRs) have been increasing since 2002. Following information about causes, incidence and risk factors collected from the scientific community, the Italian Ministry of Health submitted Ministerial Recommendation no. 10.
Purpose To assess the effects of the submitted recommendation: by measuring ADRs due to BRONJ included in the Italian pharmacovigilance database (RNFV) from 2006 to 2012; by examining what the local health structures and hospitals (the ones with the highest numbers of ADRs) did in order to put into practice what the Ministry published.
Materials and methods We searched the RNFV database looking for all ADRs that happened between 01/01/2006 and 31/12/2012 for every active principle and included in the RNFV till 31/05/2013. We selected the following preferred terms: osteonecrosis of the jaws, osteonecrosis, osteomyelitis. ADRs were analysed by: year of onset, active principle, therapeutic indications, seriousness, health structures and reporter type. We phoned the local pharmacovigilance manager (RLFV) to collect information on how the Ministerial recommendation has been put into practice.
Results We found 683 reports and they came from 94 health structures (33% from the RLFV). In 98% (671) of the reports the suspect drug is at least one bisphosphonate (BP) (zoledronic acid in 74.5%) and 67.5% of the reports come from 10, mainly academic, health structures. Four of these have produced an internal procedure and 2 started an education plan. Since 2009 we can observe a gradual decrease in the following parameters: number of reports and number of reports coming from health structures; reports coming from dentists; the percentage of ADRs in the oncological area versus all the other diseases in which BPs are used (86.2% in 2006 and 72.9% in 2012); percentage of BRONJ associated with BP-related ADRs (103 out of 157, equal to 65.6% in 2006, and 61 out of 182 equal to 33.5% in 2012). The consumption of zoledronic acid has not decreased in the time interval analysed. 40% of the ADRs happened between 2006 and 2009 had been included in the database after the recommendation’s submission.
Conclusions The well-known problem of under-reporting is clearly apparent. The increased notoriety of this ADR, also due to the Ministerial Recommendation, draws attention to all BPs. The Ministerial Recommendation has succeeded in reducing BRONJ cases due to increased preventative measures. It has stimulated the recovery of ADRs that had happened in previous years and has given a good stimulus to good practice in pharmacovigilance, an important jigsaw piece that has proved efficient in the management of clinical risk for the safer use of drugs.
No conflict of interest.
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