BMJ  2006;333:982-983 (11 November), doi:10.1136/bmj.39024.647558.BE

Editorials

Osteonecrosis of the jaw after treatment with bisphosphonates

Is irreversible, so the focus must be on prevention

New generation bisphosphonates such as zolendronic acid, pamidronate, and alendronic acid have various indications in medicine. Initially, their use was restricted to patients with metastatic bone malignancy secondary to breast cancer, lung cancer, prostate cancer, or multiple myeloma. Their benefit in these conditions led to wider application for other bone pathologies, such as osteoporosis and Paget's disease.¹ Their main effect is to inhibit osteoclast activity; however, they also seem to have antiangiogenic effects,² and once they are incorporated into the bony matrix, degradation is minimal.³

Reports from several hundred cases over the past three years suggest that long term use of new generation bisphosphonates increases the risk of avascular osteonecrosis of the jaws.^{4 5 6} The mean onset time of osteonecrosis after the treatment is started is one to three years.⁶ The clinical picture consists of non-healing ulcerated oral lesions and visible necrotic bone, which are sometimes associated with a diffuse jaw or facial pain. Osteonecrotic side effects are relatively rare in patients taking these drugs, and risk is related to the type of drug and the doses given (incidence estimated 1-10%).⁷ Although rare, these side effects are clinically difficult to manage.⁶ Such side effects should be considered when new generation bisphosphonates are prescribed for patients without cancer who have better long term survival and thus increased risk of developing delayed osteonecrosis.⁸

So, is it possible to prevent avascular osteonecrosis? Two recent studies concluded that it cannot be avoided completely.^{6 8} These studies identified (potentially modifiable) risk factors that increased the risk of avascular maxillo-mandibular osteonecrosis, such as poor dental hygiene, periodontal problems, dental extractions, and oral surgery.

Currently, discontinuation of new generation bisphosphonates, treatment with long term antibiotics, and careful surgical debridement may limit osteonecrosis, but no treatment can totally reverse it. We therefore recommend that patients should be referred for a specialist dental or maxillofacial opinion, so that chronic periodontal problems and foreseeable dental extractions can be considered before treatment is started. The importance of good dental hygiene should be emphasised, and patients should be made fully aware of the benefits and harms so that they can make an informed decision about whether they should start treatment.

¹ Department of Oral and Maxillo-Facial Surgery, University Hospital of Geneva, 1211 Geneva, Switzerland

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Competing interests: None declared.

References

1. Drake WM, Kendler DL, Brown JP. Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual foothills meeting on osteoporosis, Calgary, Alberta, Canada, September 9-10, 2000. Clin Ther 2001;23:620-6.[CrossRef][ISI][Medline]
2. Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055-61.[Abstract/Free Full Text]
3. Lin JH, Russell G, Gertz B. Pharmacokinetics of alendronate: an overview. Int J Clin Pract 1999;101(suppl):18-26.
4. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7.[CrossRef][ISI][Medline]
5. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62:527-34.[CrossRef][ISI][Medline]
6. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567-75.[CrossRef][ISI][Medline]
7. Woo SB, Hellstein JW, Kalmar JR. Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144:753-61.[Abstract/Free Full Text]
8. Farrugia MC, Summerlin DJ, Krowiak E, Huntley T, Freeman S, Borrowdale R, et al. Osteonecrosis of the mandible or maxilla associated with the use of new generation biphosphonates. Laryngoscope 2006;116:115-20.[CrossRef][ISI][Medline]

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