title: Bisphosphonate-related osteonecrosis of the jaw: an Italian post-marketing surveillance analysis.
abstract: OBJECTIVE
  Although bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is well recognized, little is known about it in terms of pathophysiology, epidemiology or management. We analyzed all suspected BRONJ reports sent to the Italian Pharmacovigilance Adverse Event Spontaneous Reporting System (Rete Nazionale Farmacovigilanza [RNF]) to determine their pattern and add new information about this relevant issue.
  
  
  METHODS
  All suspected BRONJ sent to the RNF between 2003 and 2011 were retrieved. After a case-by-case assessment procedure, we analyzed BP type, BP exposure time and time since last use.
  
  
  RESULTS
  Between 2003 and 2011, 555 reports of osteonecrosis of the jaw (ONJ) after BP administration were recorded in the RNF. These events occurred mostly in patients affected by cancer (77.84%) in which zoledronate was the most frequently suspected BP. Most patients experienced ONJ after long-term use of the drug (median time of BP exposure being between 1.3 and 8.8 years). Interestingly, 139 (25.05%) cases of ONJ occurred between 2 and 121 months after BP withdrawal.
  
  
  CONCLUSIONS
  This study shows that BRONJ can occur much earlier than hitherto reported, adds new data on BRONJ onset following ibandronate treatment and reveals that patients who cease BP-based therapy develop ONJ, raising the question of post-treatment monitoring strategies.
authors.affiliation: Second University of Naples, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine , Naples , Italy elisabetta.parretta@unina2.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Parretta
authors.forename: Laura
authors.initials: L
authors.lastname: Sottosanti
authors.forename: Liberata
authors.initials: L
authors.lastname: Sportiello
authors.forename: Concetta
authors.initials: C
authors.lastname: Rafaniello
authors.forename: Simona
authors.initials: S
authors.lastname: Potenza
authors.forename: Salvatore
authors.initials: S
authors.lastname: D'Amato
authors.forename: Rocio
authors.initials: R
authors.lastname: González-González
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colella
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capuano
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology* / Q000209:etiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: bisphosphonates; osteonecrosis of the jaw; osteonecrosis of the jaw monitoring; spontaneous reporting