Osteonecrosis of the Jaw and Bisphosphonates: Fellows Conference Review
April 2009
Debra Bynum
Definition:
1. Clear definition lacking
2. American Society for Bone and Mineral Research (ASBMR) task force on ONJ: “area of exposed
bone in the maxillofacial region that has not healed within 8 weeks after identification by a
healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has
not had radiation therapy to the craniofacial region.”
3. Key point: exposed bone
Clinical Presentation:
1. Pain, swelling, evidence of infection
2. Role of bacterial infection unclear (whether it initiates or is a result of…)
3. Ulcerated area with exposed bone usually seen, but may have time period before this is seen (ADA
states that absence of exposed bone does NOT rule out ONJ/BON, although most other working
groups use the presence of exposed bone in their definition)
4. Often at site of previous tooth extraction/dental work
5. May be asymptomatic and discovered on routine dental exam
6. May progress to include necrotic bone with pain, prululent drainage, pathologic fracture, extraoral
fistula, or osteolysis
Epidemiology: How common is it?
1. Difficult to know really because most data comes from surveys, many of which have been web
based
2. Limitations of web based surveys: differing definitions, selection bias, unreliability of self reported
data, lack of objective evaluation of cases
3. May be as high as 1-10 per 100 patients with underlying malignancy who receive high cumulative
doses of IV bisphosphonates
4. ASBMR task force on ONJ conducted literature review of published and unpublished data and
concluded that the risk with oral bisphosphonate for osteoporosis was very low (somewhere
between 1 in 10,000 to < 1 in 100,000 patient-treatment years)
5. Data from Randomized Clinical Trials: HORIZON –Pivotal Fracture Trial (zoledronic 5 mg once
yearly)
a. Over 7,000 women reviewed
b. 1 case in zoledronic acid group and 1 case in placebo group felt to meet criteria for ONJ
(NO increase in risk in this study)
Why does it develop?
1. Short answer: we do not know…
2. Theories:
a. Initial damage to oral mucosa
b. Reduced bone turnover leading to increased “microfractures” (problem, this is not really
seen on path, and not seen at all on random biopsies from other bone sites in women on
bisphosphonates when compared to those not on)
c. ?antiangiogenic effects
d. ?other risk factors such as dental trauma and other medical illnesses
What is the CTx and does this help identify people at risk for ONJ?
1. C-terminal telopeptide
2. Interest in using this to identify people at higher risk
3. marker of bone resorption/turnover
4. lower in patients on bisphosphonates
5. levels under 100: higher risk; those over 150, low risk for developing ONJ
6. Authors of one study recommended patients with low levels who are at higher risk have a “drug
holiday” before doing any significant dental work
7. clinically not very helpful: patients on bisphosphonates have lower levels…
Treatment
1. Oral antimicrobial rinses
2. Systemic antibiotics if evidence for infection
3. Conservative or delayed surgical treatment
4. Some patients may require segmental jaw resection
5. Not clear that stopping the bisphosphonate does anything to reverse ONJ -- ASBMR
recommends continuing treatment in patients who are at high risk without these agents (those
with myeloma or severe metastatic cancer)
Silverman SL, Landesberg R. Osteonecrosis of the Jaw and the Role of Bisphosphonates: A Critical
Review. Am J Med (2009) 122, S33-S45.