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Bisphosphonates and Osteonecrosis of the Jaw

Sook-Bin Woo, DMD; John W. Hellstein, DDS, MS; and John R. Kalmar, DMD, PhD
[+] Article, Author, and Disclosure Information

From Brigham and Women's Hospital and Harvard School of Dental Medicine, Boston, Massachusetts; University of Iowa College of Dentistry, Iowa City, Iowa; and The Ohio State University College of Dentistry, Columbus, Ohio.

Potential Financial Conflicts of Interest:Grants received: S.-B. Woo (Novartis).

Ann Intern Med. 2006;145(10):792. doi:10.7326/0003-4819-145-10-200611210-00023
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Bisphosphonate-Associated Osteonecrosis of the Jaw
Posted on December 21, 2006
Michael Pazianas
Univ of Pennsylvania
Conflict of Interest: None Declared

Woo and colleagues (1) in his recent review article and a numerous reviews (2,3) in a host of scientific journals failed to comment on the potential contribution of ischemia induced by the injection of a vasoconstrive agent during an oral procedure.

Today's limited existing data on Bisphosphonate-Associated Osteonecrosis of the Jaw (BONJ) has identified both advanced age (>65 years) and jaw surgery as risk factors frequently present at the time of BONJ diagnosis. Advanced age, however, may only be a condition in so far as it is characterized by weak, low activity bone structure. In these patients, bone turnover has also been further reduced by the administration of bisphosphonates (4), irrespective of route. IV administration though has the greatest impact as it bypasses the intestinal barrier to allow >50% of the drug to directly reach the skeleton. Moreover, patients with significant renal insufficiency experience even higher bisphosphonate concentrations, which further impede bone turnover.

We believe that temporary local jaw ischemia, induced by routine injections of vasoconstrictive agents protecting against excessive bleeding in jaw surgery, virtually ensures the development of osteonecrosis in individuals described above. Therefore, we recommend the avoidance of these injections for patients on IV bisphosphonates and especially for the elderly with depleted bone mass and reduced renal function until the causes of BONJ have been determined.


1. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753-61.

2. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006;7:508-514

3. American Dental Association Council on Scientific Affairs. Dental management of patients receiving oral bisphosphonate therapy: expert panel recommendations. J Am Dent Assoc. 2006;137:1144-1150

4. Roelofs AJ, Thompson K, Gordon S, Rogers MJ. Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res. 2006;12(20 Pt 2):6222s-6230s

Conflict of Interest:

Roche Consultancy

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