Bisphosphonate-associated osteonecrosis of the jaws
Encyclopedia
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
.
, of the jaw
s is a rare potential complication in cancer
patients receiving treatments including radiation
, chemotherapy
, or in patients with tumor
s 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
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.
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.
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:
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.
), Actonel (risedronate
) and Boniva
(ibandronate).
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.
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
phenomenon that may lead to surgical complication in the form of impaired wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
following oral or periodontal surgery or endodontic therapy
Endodontic therapy
Endodontic therapy is a sequence of treatment for the pulp of a tooth which results in the elimination of infection and protection of the decontaminated tooth from future microbial invasion...
.
There is presently no known prevention for bisphosphonate-associated osteonecrosis of the jaw.
For more general information, see Osteonecrosis of the jaw
Osteonecrosis of the jaw
Osteonecrosis of the jaw is a severe bone disease that affects the maxilla and the mandible. Various forms of ONJ have been described over the last 160 years, and a number of causes have been suggested in the literature...
.
Definition
Osteonecrosis, or localized death of bone tissueBone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
, of the jaw
Jaw
The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term jaws is also broadly applied to the whole of the structures constituting the vault of the mouth and serving to open and close it and is part of the body plan of...
s is a rare potential complication in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
patients receiving treatments including radiation
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, or in patients with tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s 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
Bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
. Matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....
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.
In response to the growing base of literature on this association, the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
Food and Drug Administration issued a broad drug class warning of this complication for all bisphosphonates in 2005.
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 osteoclastOsteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
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
Diagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
of bisphosphonate-associated osteonecrosis of the jaw relies on three criteria:
- the patient possesses an area of exposed bone in the jaw persisting for more than 8 weeks,
- the patient must present with no history of radiation therapyRadiation therapyRadiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
to the head and neck, - 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
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
of and the length of exposure
Time
Time is a part of the measuring system used to sequence events, to compare the durations of events and the intervals between them, and to quantify rates of change such as the motions of objects....
to bisphosphonates are linked to the risk
Risk
Risk is the potential that a chosen action or activity will lead to a loss . The notion implies that a choice having an influence on the outcome exists . Potential losses themselves may also be called "risks"...
of developing bisphosphonate-associated osteonecrosis of the jaw.
Bisphosphonates: intravenous vs. oral
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 (alendronateAlendronate
Alendronic acid or alendronate sodium — sold as Fosamax by Merck — is a bisphosphonate drug used for osteoporosis and several other bone diseases. It is marketed alone as well as in combination with vitamin D . Merck's U.S...
), Actonel (risedronate
Risedronate
Risedronic acid or risedronate sodium is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Paget's disease of bone. It is produced and marketed by Warner Chilcott, Sanofi-Aventis, and in Japan by Takeda under the trade names Actonel, Atelvia, and Benet...
) and Boniva
Ibandronic acid
Ibandronic acid or ibandronate sodium , marketed under the trade names Boniva, Bondronat and Bonviva, is a potent bisphosphonate drug used in the prevention and treatment of osteoporosis....
(ibandronate).
Risk
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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
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
- Osteonecrosis of the jawOsteonecrosis of the jawOsteonecrosis of the jaw is a severe bone disease that affects the maxilla and the mandible. Various forms of ONJ have been described over the last 160 years, and a number of causes have been suggested in the literature...
, see section on Bisphosphonates - Phossy jawPhossy jawPhossy jaw, formally phosphorus necrosis of the jaw, is an occupational disease of those who work with white phosphorus, also known as yellow phosphorus, without proper safeguards. It was most commonly seen in workers in the match industry in the 19th and early 20th century...
- C-terminal telopeptideC-terminal telopeptideIn bone physiology, the C-terminal telopeptide is a serum biomarker used to measure the rate of bone turnover...
, commonly known as CTX, a serum biomarker for bone turnover rate and a tool used to evaluate patient risk for complications due to BRONJ