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Bisphosphonate Osteonecrosis

Bisphosphonate-associated osteonecrosis of the jaw, often abbreviated as BON, BON of the jaw or even BRONJ, is a recently discovered dental phenomenon that may lead to surgical complication in the form of impaired wound healing following oral or periodontal surgery or endodontic therapy.  There is presently no known prevention for bisphosphonate-associated osteonecrosis of the jaw.  For more general information, see Osteonecrosis of the jaw.

Osteonecrosis, or localized death of bone tissue, of the jaws is a rare potential complication in cancer patients receiving treatments including radiation, chemotherapy, or in patients with tumors or infectious embolic events. In 2003, reports surfaced of the increased risk of osteonecrosis in patients receiving these therapies concomitantant with and an intravenous bisphosphonate.  Matrix metalloproteinase may be a candidate gene for bisphosphonate-associated osteonecrosis of the jaws, since it is the only gene known to be associated with both bone abnormalities and atrial fibrillation, another side effect of bisphosphonates.  In response to the growing base of literature on this association, the United States Food and Drug Administration issued a broad drug class warning of this complication for all bisphosphonates in 2005.

Although the methods of action are not yet completely understood, it is hypothesized that bisphosphonate-associated osteonecrosis of the jaw is related to a defect in jaw bone physiologic remodeling or wound healing. The strong inhibition of osteoclast function precipitated by bisphosphonate therapy can lead to inhibition of normal bone turnover. Because bisphosphonates are preferentially deposited in bone with high turnover rates, it is possible that the levels of bisphosphonate within the jaw are selectively elevated. To date, there has been no reported cases of bisphosphonate-associated complications within bones outside the craniofacial skeleton.

A diagnosis of bisphosphonate-associated osteonecrosis of the jaw relies on three criteria:

1. the patient possesses an area of exposed bone in the jaw persisting for more than 8 weeks,
2. the patient must present with no history of radiation therapy to the head and neck,
3. the patient must be taking or have taken bisphosphonate medication.

According to the updated 2009 BRONJ Position Paper published by the American Association of Oral and Maxillofacial Surgeons, both the potency of and the length of exposure to bisphosphonates are linked to the risk of developing bisphosphonate-associated osteonecrosis of the jaw.

Cases of BON have also been associated with the use of the following two intravenous and three oral bisphosphonates, respectively: Zometa (zoledronic acid) and Aredia (pamidronate) & Fosamax (alendronate), Actonel (risedronate) and Boniva (ibandronate).

The overwhelming majority of BON diagnoses, however, were associated with intravenous administration of bisphosphonates (94%). Only the remaining 6% of cases arose in patients taking bisphosphonates orally.  Although the total United States prescriptions for oral bisphosphonates exceeded 30 million in 2006, less than 10% of BON cases were associated with patients taking oral bisphosphonate drugs.  Studies have estimated that BON occurs in roughly 20% of patients taking intravenous zoledronic acid for cancer therapy and in between 0-0.04% of patients taking orally administered bisphosphonates.

See also

1. Osteonecrosis of the jaw, see section on Bisphosphonates
2. Phossy jaw
3. C-terminal telopeptide, commonly known as CTX, a serum biomarker for bone turnover rate and a tool used to evaluate patient risk for complications due to BRONJ