Bisphosphonate-associated osteonecrosis of the jaw

Bisphosphonate-associated osteonecrosis of the jaw (often abbreviated as BON, BONJ, or BON of the jaw), also called bisphosphonate-related osteonecrosis of the jaw (BRONJ) (pronounced /brɒndʒ/) or bisphosphonate-induced osteonecrosis of the jaw (BIONJ), is osteonecrosis of the jaw in a person with a history of bisphosphonate use who undergoes subsequent dental surgery. It may lead to surgical complication in the form of impaired wound healing following oral and maxillofacial surgery, periodontal surgery, or endodontic therapy.^[1]

A correlation between history of bisphosphonate use and osteonecrosis of the jaw after later surgery was detected in the oral medicine fields for several years before the exact nature of the relationship (etiology, pathogenesis) could begin to be understood, and it is still not entirely clear, although a similarity with phossy jaw is recognized. There is no known prevention for bisphosphonate-associated osteonecrosis of the jaw.^[2] Avoiding the use of bisphosphonates is not a viable prevention on a general-population basis because the drugs have more benefit throughout the population (preventing osteoporotic fractures and treating bone cancers) than harm (BRONJ).

Definition

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,^[3][4] reports surfaced of the increased risk of osteonecrosis in patients receiving these therapies concomitant with intravenous bisphosphonate.^[5] Matrix metalloproteinase 2 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.^[6]

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.^[7]

Pathogenesis and diagnosis

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.^[7]

A diagnosis of bisphosphonate-associated osteonecrosis of the jaw relies on three criteria:^[2]

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.^[8]

Clinical presentation

• Pain and neuropathy^[9]
• Erythema and suppuration
• Halitosis

Bisphosphonates: intravenous vs. oral

Cases of BRONJ 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).^[10]

Risk

The overwhelming majority of BRONJ diagnoses, however, were associated with intravenous administration of bisphosphonates (94%). Only the remaining 6% of cases arose in patients taking bisphosphonates orally.^[2]

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.^[11] Studies have estimated that BRONJ 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.^[12]

Owing to prolonged embedding of bisphosphonate drugs in the bone tissues, the risk for BRONJ is high even after stopping the administration of the medication for several years.^[13]

Treatment and outcomes

Treatment usually involves antimicrobial mouth washes and oral antibiotics to help the immune system fight the attendant infection, and it also often involves local resection of the necrotic bone lesion. Many patients with BRONJ have successful outcomes after treatment, meaning that the local osteonecrosis is stopped, the infection is cleared, and the mucosa heals and once again covers the bone.

See also

• Osteonecrosis of the jaw, see section on Bisphosphonates
• Phossy jaw
• 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

External links

• http://www.ada.org/sections/professionalResources/pdfs/topics_ARONJ_report.pdf

References