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Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®): Supportive care - Health Professional Information [NCI] - Oral Toxicities Not Related to Chemotherapy or Radiation Therapy

Osteonecrosis of the Jaw Associated With Medications (ONJ)

The first reported cases of osteonecrosis of the jaw associated with medications (ONJ) were seen in patients taking bisphosphonates.[1,2,3] Bisphosphonates are potent inhibitors of osteoclasts. They are used in cancer patients with skeletal metastasis, including breast, prostate, or lung cancer; and in patients with multiple myeloma. Bisphosphonates are also used to treat hypercalcemia of malignancy. Bisphosphonates reduce the risk of fracture and skeletal pain, improving the quality of life of patients with malignant bone disease.[4] (Refer to the PDQ summary on Pain for more information.)

Evidence in the medical and dental literature reveals several cases of ONJ reported with the use of drugs other than bisphosphonates, including the following:[5,6]

  • Denosumab, a human monoclonal antibody that inhibits the receptor activator of nuclear factor kappa beta ligand (RANKL).
  • The antiangiogenic drugs being tested in advanced cancer cases, including bevacizumab, sunitinib, and possibly sorafenib.

Table 5. Drugs and Biologics Used in Oncology and Reported to Be Associated With ONJ

Drug Generic (Trade Name) Manufacturer (Indication) Class of Drug Mode of Action Reported to Cause ONJ?
GIST = gastrointestinal stromal tumor; ONJ = osteonecrosis of the jaw associated with medications; RANKL = receptor activator of nuclear factor kappa beta ligand; VEGF = vascular endothelial growth factor.
Zoledronic acid (Zometa, Reclast) Novartis (bone metastasis; bone loss from cancer therapy) Bisphosphonate (antiresorptive) Inhibition of osteoclasts Yes
Pamidronate (Aredia) Novartis Bisphosphonate (antiresorptive) Inhibition of osteoclasts Yes
Alendronate (Fosamax) Merck (bone loss from cancer therapy) Bisphosphonate (antiresorptive) Inhibition of osteoclasts Yes
Denosumab (Prolia, XGeva) Amgen, Inc. (bone metastasis; osteoporosis; bone loss from cancer therapy) Humanized monoclonal antibody (antiresorptive) Suppression of bone remodeling by inhibition of RANKL Yes
Bevacizumab (Avastin) Genentech BioOncology (advanced cancers: metastatic colorectal cancer; nonsquamous non-small cell lung cancer; metastatic breast cancer; glioblastoma; metastatic renal cell carcinoma) Antiangiogenic Inhibition of angiogenesis by blocking the action of VEGF Yes
Sunitinib (Sutent) Pfizer Oncology (advanced renal cell carcinoma; GIST) Antiangiogenic Inhibition of angiogenesis by blocking VEGF tyrosine kinase Yes
Sorafenib (Nexavar) Bayer Health Care Pharmaceuticals (renal cell carcinoma; hepatocellular carcinoma) Antiangiogenic Inhibition of angiogenesis by blocking VEGF tyrosine kinase Yes, when combined with antiresorptives
1 | 2 | 3 | 4 | 5 | 6 | 7
1 | 2 | 3 | 4 | 5 | 6 | 7
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