Bisphosphonate-related osteonecrosis of the jaw (BONJ) is a condition characterized by exposure of the jawbones in a patient who has been taking bisphosphonates but who has not had a history of radiation to the area. This generally occurs in adults, mainly because bisphosphonates are usually taken by adults. It occurs in two populations, those with osteoporosis (mostly postmenopausal women) and those with cancer involving the bones such as myeloma and metastatic tumors.
Approximately one-half to two-thirds of lesions are painful. The first complaint may be pain not at the site of exposed bone, but rather on the tongue because of trauma from sharp edges of the bone on the lingual mandible causing ulceration of the tongue ventrum.
BONJ is most commonly seen in patients using high doses of intravenous bisphosphonates for oncology purposes; the risk is directly related to cumulative dose. Bisphosphonates are powerful osteoclast inhibitors and therefore suppress bone turnover. A possible theory of pathogenesis suggests that when there is an increased need for bone turnover, such as in surgery to the jaws, and the jawbone is unable to meet this requirement, the bone becomes necrotic. Most recently, local infection by oral bacteria has been shown to play an important role. It is likely that lesions result from both mechanisms. Anti-angiogenesis also plays a role but it is unclear to what extent.
Oral preparations (such as alendronate) have been used for more than a decade for the prevention of fractures in patients with osteoporosis. The more powerful and better absorbed intravenous bisphosphonates (such as zoledronic acid and pamidronate) are used to reduce skeletal-related events related to bone malignancies such as multiple myeloma and metastatic tumors to the bone (especially metastatic breast and prostate cancer). Secondary actions of bisphosphonates such as anti-angiogenic and tumoricidal activity as well as activation of the immune system may also play a role in control of such skeletal-related events.
Predisposing factors include tooth extraction or other form of dento-alveolar surgery, intravenous preparations used in oncology treatment doses, and odontogenic infection. Other comorbidities may include diabetes and smoking.
A common presentation is a history of a dental extraction (present in 60% of cases) with poor healing or non-healing of the extraction socket so that months later, there is exposed bone within the socket or in the surrounding jawbone. This usually persists for months and years with spontaneous exfoliation of pieces of bone over time. Teeth associated with BONJ may also spontaneously exfoliate.
Codes
ICD10CM: M87.180 – Osteonecrosis due to drugs, jaw
SNOMEDCT: 293295008 – Adverse reaction caused by bisphosphonate
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Differential Diagnosis & Pitfalls
All of the following look similar to BONJ but lack an association of exposure to bisphosphonates:
Osteonecrosis has been seen in patients on other medications such as bevacizumab, sunitinib, and denosumab.
Osteoradionecrosis (radiation-induced osteonecrosis of the jaws) is almost identical in presentation except for the history of exposure to radiation to the jaws, a male predilection, and involvement of the mandible in 70% to 80% of cases.
Odontogenic infections may lead to osteomyelitis and sequestrum formation, although the necrotic bone is usually seen on radiograph rather than exposed. Such osteomyelitis is particularly seen in patients with pre-existing fibro-osseous lesions such as mature cemento-osseous dysplasia.
Trauma to the mylohyoid ridge may lead to benign spontaneous sequestration of the lingual plate; a similar appearance may be seen after intubation for general anesthesia.
Herpes zoster-induced osteonecrosis of the jaws (a rare complication of zoster infection) is associated with pain and ulceration on one side of the jaw and subsequent breakdown of the underlying mucosa and bone exposure.
Necrotizing ulcerative periodontitis is seen primarily in patients with HIV infection and presents with necrosis and exposure of the bone; it is probably associated with the inability of the patient to combat a polymicrobial periodontal infection because of immune suppression.
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
