title: Bisphosphonates and oral cavity avascular bone necrosis: a review of twelve cases.
abstract: BACKGROUND
  Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws.
  
  
  METHODS
  The data for twelve patients, referred to either an oral and maxillofacial surgeon or to an oral medicine specialist for the management of clinically apparent chronic oral osteonecrosis of unknown etiology, were reviewed. All had received cancer-related therapy simultaneously with bisphosphonate management.
  
  
  RESULTS
  The typical presenting symptoms were pain and exposed bone at the site of a previous tooth extraction. In most patients, the lesions initially occurred after dental extraction or other odontostomatological procedures, while five had a spontaneous event. Biopsy of the involved area showed the presence of necrotic lacunae, with infiltration of lymphocytes and histiocytes. In nine cases, there was histological or cytological diagnosis of suspicious osteomyelitis. No correlation was observed between the intraoral lesions and myelosuppression secondary to antineoplastic therapy.
  
  
  CONCLUSIONS
  Based on the patients' respective histories, clinical presentations and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrotic process is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates compromise bone vascularity may be related to their effect on the osteoclasts. The potent bisphosphonate-mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of the bone.
authors.affiliation: Department of Medical Oncology, Hospital A. Fiorini, Terracina, Italy.
authors.forename: Nello
authors.initials: N
authors.lastname: Salesi
authors.forename: Roberto
authors.initials: R
authors.lastname: Pistilli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marcelli
authors.forename: Flavio Andrea
authors.initials: FA
authors.lastname: Govoni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bozza
authors.forename: Giandominik
authors.initials: G
authors.lastname: Bossone
authors.forename: Viola
authors.initials: V
authors.lastname: Venturelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Cocco
authors.forename: Umberto
authors.initials: U
authors.lastname: Pacetti
authors.forename: Alida
authors.initials: A
authors.lastname: Ciorra
authors.forename: Concetta
authors.initials: C
authors.lastname: Di Fonso
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Enzo
authors.initials: E
authors.lastname: Veltri
authors.forename: Aldo
authors.initials: A
authors.lastname: Vecchione
mesh_terms: D000368:Aged; D001706:Biopsy; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008336:Mandibular Diseases / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D014081:Tooth Extraction / Q000009:adverse effects
chemical_list: D004164:Diphosphonates