Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone

An emerging oral complication of supportive cancer therapy


  • Cesar A. Migliorati D.D.S., M.S., Ph.D.,

    Corresponding author
    1. Department of Diagnostic Sciences, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida
    • Department of Diagnostic Sciences, Nova Southeastern University College of Dental Medicine, 3200 S. University Drive, Fort Lauderdale, FL 33328-2018
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    • Fax: (954) 262-1782

  • Mark M. Schubert D.D.S., M.S.D.,

    1. Department of Oral Medicine, School of Dentistry, University of Washington, Seattle, Washington
    2. Oral Medicine Service, Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center, Seattle, Washington
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  • Douglas E. Peterson D.M.D., Ph.D.,

    1. Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut
    2. Cancer Center, University of Connecticut Health Center, Farmington, Connecticut
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  • Luis Marcelo Seneda D.D.S.

    1. Oral Medicine Clinic, Oncology Center-Hospital Sirio Libanês, São Paulo, Brazil
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The current report presented 17 patients with cancer with bone metastases and 1 patient with osteopenia who received treatment with bisphosphonates and who subsequently developed osteonecrosis of the mandible and/or maxilla.


The authors reviewed information on 18 patients who were referred to oral medicine or oral surgery specialists for evaluation and treatment of mandibular and/or maxillary bone necrosis from June 2002 to September 2004. To be included in the current review, patients must have been treated with either pamidronate or zoledronic acid to control or prevent metastatic disease, or with alendronate for osteoporosis. All patients with cancer had received chemotherapy while receiving bisphosphonate management.


The 17 patients with cancer were receiving active medical care for a malignancy. Cancer treatment included a variety of chemotherapeutic agents. They presented with metastatic disease to bone and were treated intravenously with the bisphosphonates pamidronate or zoledronic acid for a mean time of 25 months (range, 4–41 mos). There were 14 females and 4 males with a mean age of 62 years (range, 37–74 yrs). Malignancies included breast carcinoma (n = 10), multiple myeloma (n = 3), prostate carcinoma (n = 1), ovarian carcinoma (n = 1), prostate carcinoma/lymphoma (n = 1), and breast/ovarian carcinoma (n = 1). One female patient with osteopenia received alendronate. The most common clinical osteonecrosis presentations included infection and necrotic bone in the mandible. Associated events included dental extractions, infection, and trauma. Two patients appeared to develop disease spontaneously, without any clinical or radiographic evidence of local pathology. Despite surgical intervention, antibiotic therapy, hyperbaric oxygen therapy, and topical use of chemotherapeutic mouth rinses, most of the lesions did not respond well to therapy. Discontinuation of bisphosphonate therapy did not assure healing. However, 1 patient with cancer healed after discontinuation of bisphosphonate therapy for 4 months.


The findings in the patient population combined with recent literature reports suggested that bisphosphonates may contribute to the pathogenesis of the oral lesions. The risk factors and precise mechanism involved in the formation of the osteonecrosis are not known. This condition represents a new oral complication in patients with cancer and can be termed bisphosphonate-associated osteonecrosis. Lesions in patients with osteoporosis are worrisome and need to be further evaluated. Cancer 2005. © 2005 American Cancer Society.