title: Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series.
abstract: OBJECTIVE
  To report a case series of patients with the nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw-a form of jaw osteonecrosis that does not manifest with necrotic bone exposure/mucosal fenestration.
  
  
  METHODS
  Among 332 individuals referred to 5 clinical centers in Europe because of development of jawbone abnormalities after or during exposure to bisphosphonates, we identified a total of 96 patients who presented with the nonexposed variant of osteonecrosis. Relevant data were obtained via clinical notes; radiological investigations; patients' history, and referral letters.
  
  
  RESULTS
  The most common clinical feature of nonexposed osteonecrosis was jaw bone pain (88/96; 91.6%); followed by sinus tract (51%), bone enlargement (36.4%); and gingival swelling (17.7%). No radiological abnormalities were identified in 29.1% (28/96) of patients. In 53.1% (51/96) of the patients; nonexposed osteonecrosis subsequently evolved into frank bone exposure within 4.6 months (mean; 95% confidence interval; 3.6-5.6).
  
  
  CONCLUSIONS
  Clinicians should be highly vigilant to identify individuals with nonexposed osteonecrosis, as the impact on epidemiological data and clinical trial design could be potentially significant. Although the present case series represents approximately 30% of all patients with bisphosphonates-associated osteonecrosis observed at the study centers, further population-based prospective studies are needed to obtain robust epidemiological figures.
authors.affiliation: University College London Eastman Dental Institute, London, UK. s.fedele@eastman.ucl.ac.uk
authors.forename: Stefano
authors.initials: S
authors.lastname: Fedele
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Porter
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Aiuto
authors.forename: Suad
authors.initials: S
authors.lastname: Aljohani
authors.forename: Paolo
authors.initials: P
authors.lastname: Vescovi
authors.forename: Maddalena
authors.initials: M
authors.lastname: Manfredi
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Arduino
authors.forename: Roberto
authors.initials: R
authors.lastname: Broccoletti
authors.forename: Anna
authors.initials: A
authors.lastname: Musciotto
authors.forename: Olga
authors.initials: O
authors.lastname: Di Fede
authors.forename: Tony S
authors.initials: TS
authors.lastname: Lazarovici
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.forename: Naom
authors.initials: N
authors.lastname: Yarom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced* / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology; D010024:Osteoporosis / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019386:Alendronate