title: Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: definition and management of the risk related to zoledronic acid.
abstract: OBJECTIVE
  Bisphosphonates (BPs) are currently used to treat bone lesions in patients with multiple myeloma (MM). Osteonecrosis of the jaw (ONJ) has been reported as an adverse event of such treatment, especially after treatment with zoledronic acid (ZA). The aim of this study was to evaluate incidence, risk factors, management, and prevention strategies of ONJ in order to optimize the current standard use of BPs in MM.
  
  
  METHODS
  We reviewed the medical records of 105 patients with MM treated in 2 hematology departments with monthly pamidronate 90 mg and/or ZA 4 mg and evaluated for > or = 12 months. Because they are risk factors for ONJ development, we analyzed patient and disease features, previous MM treatments, type and number of BP infusions, and previous history of dental procedures.
  
  
  RESULTS
  Seventeen patients (16%) with MM treated with BPs developed ONJ after a median number of 43 BP infusions (vs. 28 in patients without ONJ; P = .035). In 11 of 17 patients, ONJ arose after a tooth extraction. Among risk factors, the administered doses of ZA were significantly associated with ONJ, and 12 consecutive doses of ZA proved to double the risk of developing this complication. Regular hard- and soft-tissue oral assessment was of benefit in the prevention of further ONJ occurrence.
  
  
  CONCLUSIONS
  The most important risk factor for ONJ is represented by the number of ZA infusions. Tooth extractions and invasive procedures should be avoided. A multidisciplinary approach including oncohematologists and dental teams proved critical to better identify, prevent, and manage ONJ.
authors.affiliation: Hematology Department, Niquarda Ca'Granda Hospital, Milano, Italy. ematologia@ospedaleniguarda.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cafro
authors.forename: Luciana
authors.initials: L
authors.lastname: Barbarano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Nosari
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Avanzo
authors.forename: Michele
authors.initials: M
authors.lastname: Nichelatti
authors.forename: Michele
authors.initials: M
authors.lastname: Bibas
authors.forename: Domenico
authors.initials: D
authors.lastname: Gaglioti
authors.forename: Alberto
authors.initials: A
authors.lastname: Taroni
authors.forename: Francesco
authors.initials: F
authors.lastname: Riva
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
authors.forename: Alessandro
authors.initials: A
authors.lastname: Andriani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D004002:Clodronic Acid / Q000627:therapeutic use*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008334:Mandible / Q000473:pathology*; D008437:Maxilla / Q000473:pathology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009336:Necrosis; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid