Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series

Am J Med. 2010 Nov;123(11):1060-4. doi: 10.1016/j.amjmed.2010.04.033. Epub 2010 Sep 28.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alendronate / adverse effects
  • Alendronate / therapeutic use
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Diphosphonates / adverse effects*
  • Diphosphonates / therapeutic use
  • Europe / epidemiology
  • Female
  • Humans
  • Jaw Diseases / chemically induced*
  • Jaw Diseases / epidemiology
  • Kidney Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Osteonecrosis / chemically induced*
  • Osteonecrosis / epidemiology
  • Osteoporosis / drug therapy
  • Prostatic Neoplasms / drug therapy
  • Time Factors


  • Bone Density Conservation Agents
  • Diphosphonates
  • Alendronate