PIC QUESTION OF THE WEEK: 5/22/06

Q: Is there a relationship between the use of alendronate and complications from dental surgery?

A: Bisphosphonates, including alendronate (Fosamax), have been associated with the development of osteonecrosis of the jaw in patients undergoing various dental procedures, primarily tooth extraction. Osteonecrosis presents as exposure of the mandible or maxilla and may be painful or painless. The condition is most commonly reported in patients receiving intravenous bisphosphonates such as pamidronate (Aredia) and zoledronic acid (Zometa) for hypercalcemia secondary to multiple myeloma and breast cancer. Some cases of osteonecrosis of the jaw have, however, been reported in patients not undergoing dental procedures as well as those without malignancy. A precaution is included in the product labeling for each of the available bisphosphonates and describes the known risk factors for this complication. These include a diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids, anti-angiogenic compounds such as thalidomide, poor oral hygiene and/or pre-existing dental disease, anemia, coagulopathy, and infection. It is unknown whether discontinuation of bisphosphonate therapy reduces the risk of osteonecrosis of the jaw. It is recommended that invasive dental procedures be avoided, if possible, during treatment with bisphosphonates. These compounds inhibit osteoclastic activity. Their long-term use decreases bone turnover, but subsequently can interfere with the healing of bone even after minor injury (e.g. tooth extraction or denture injury, infection, etc.). The anti-angiogenic effect of bisphosphonates may also contribute to local ischemia and tissue injury. In one review, 119 patients exposed to bisphosphonates developed osteonecrosis/osteopetrosis of the jaw. With the exception of three patients receiving alendronate for osteoporosis, all others had a diagnosis of multiple myeloma (52%), metastatic breast cancer (42%), or prostate cancer (3.4%) and received bisphosphonates for hypercalcemia. Almost all patients had existing dental conditions that increased their risk for developing osteonecrosis. The authors concluded that pre-therapy dental care could reduce the incidence of this complication, but was unlikely to completely prevent it. Antimicrobial therapy and chlorhexidine mouthwash might be useful in reducing pain in patients with exposed bone. It has been estimated that the incidence of osteonecrosis of the jaw is 10% with zoledronic acid and 4% with pamidronate. Although rare, there are approximately 15 case reports of non-cancer patients with osteoporosis who developed osteonecrosis while receiving alendronate. In conclusion, osteonecrosis of the jaw is a well documented but often unappreciated complication of bisphosphonate treatment. (NOTE: On the day of this publication, a major review of bisphosphonates and osteonecrosis appeared in Annals of Internal Medicine, 2006;144:753-61.)

References:

• Marx RE, Sawatari Y, Fortin M, et al. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567-75.

• Sarathy AP, Bourgeois SL, Goodell GG. Bisphosphonate-associated osteonecrosis of the jaws and endodontic treatment: two case reports. J Endod 2005;31:759-63.

• Durie BGM, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl Med 2005;353:99-100.

Alyssa M. Stein, Pharmacy Clerkship Student The PIC Question of the Week is a publication of the Pharmaceutical Information Center, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282