Bisphosphonate-associated Osteonecrosis: A Long-Term Complication of Bisphosphonate Treatment

Lancet Oncol. 2006 Jun;7(6):508-14. doi: 10.1016/S1470-2045(06)70726-4.


We present current knowledge of bisphosphonate-associated osteonecrosis, a new oral complication in oncology. It was first described in 2003, and hundreds of cases have been reported worldwide. The disorder affects patients with cancer on bisphosphonate treatment for multiple myeloma or bone metastasis from breast, prostate, or lung cancer. Bisphosphonate-associated osteonecrosis is characterised by the unexpected appearance of necrotic bone in the oral cavity. Osteonecrosis can develop spontaneously or after an invasive surgical procedure such as dental extraction. Patients might have severe pain or be asymptomatic. Symptoms can mimic routine dental problems such as decay or periodontal disease. Intravenous use of pamidronate and zoledronic acid is associated with most cases. Other risk factors include duration of bisphosphonate treatment (ie, 36 months and longer), old age in patients with multiple myeloma, and a history of recent dental extraction. We also discuss pathobiology, clinical features, management, and future directions for the disorder.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Bone Density Conservation Agents / adverse effects*
  • Bone Neoplasms / drug therapy
  • Dental Care for Chronically Ill
  • Diphosphonates / adverse effects*
  • Humans
  • Imidazoles / adverse effects
  • Jaw / drug effects
  • Jaw / pathology
  • Mandibular Diseases / chemically induced*
  • Mandibular Diseases / pathology
  • Multiple Myeloma / drug therapy
  • Osteonecrosis / chemically induced*
  • Osteonecrosis / pathology
  • Pamidronate
  • Practice Guidelines as Topic
  • Time Factors
  • Zoledronic Acid


  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • Pamidronate