Dr. Richard L. Wynn is Professor of Pharmacology at the University of Maryland Dental School. He holds a BS degree in pharmacy and a PhD degree in pharmacology. More »He chaired the Department of Pharmacology at the University of Maryland Dental School from 1980 to 1995. He is the lead author of the Drug Information Handbook for Dentistry, co-author of many other dental drug publications, author of over 300 refereed scientific journal articles, consultant to the Academy of General Dentistry, featured columnist, and a featured speaker presenting more than 500 courses in continuing dental education. One of his primary interests continues to be keeping dental professionals informed of all aspects of drug use in dental practice.
Fosamax® and Osteonecrosis of the Jaw – Some New and Frequently Asked Questions
The alendronate (Fosamax®) drugs, known as the oral bisphosphonates, continue to be the cornerstones of treatment for prevention of osteoporosis. Unfortunately, they are associated with osteonecrosis of the jaw bone (ONJ), particularly if dental surgery is performed in long-term Fosamax users. Many questions have risen relative to the incidence, risk factors, mechanism of ONJ, symptoms of ONJ, and whether discontinuation of the drugs prior to dental surgery reduces risks of ONJ. All these questions and more are answered below.
1. According to the experts, what is the incidence of osteonecrosis of the jaw in Fosamax users?
Presently, the current estimates of the frequency of occurrence of ONJ in oral bisphosphonate users are the following. The American Dental Association has stated (and described in a previous newsletter) that the incidence is estimated to be 0.7 cases in 100,000 person years of exposure to oral bisphosphonates. The Medical Consultants of Consumer Reports On-Health Bulletin reported an incidence of 1 case for every 20,000 users of oral bisphosphonates (0.005%). A recent report from Australia estimated that the frequency of ONJ in osteoporotic patients, mainly on weekly oral alendronate (Fosamax), ranged from a minimum of 1 in 8,470 to a maximum of 1 in 2,260 (0.01% to 0.04%) patients. If extractions were performed, the frequency increased from 0.09% to 0.34%.
2. What numbers can I use to tell the dental patient their risk of developing ONJ with Fosamax?
The ADA suggests that the patient be informed that there is a very low risk of developing ONJ. The true risk posed by oral bisphosphonates remains uncertain, but researchers agree that it appears to be very small. All the data seem to point to a risk of approximately 0.1% of total users and that the risk increases with dental extractions to approximately 0.5%. Also, be aware that the risks of developing ONJ can be minimized but never totally eliminated. Good oral hygiene along with regular dental care is the best way to lower the risk of developing ONJ.
3. Is the risk of acquiring osteonecrosis of the jaw bone diminished with the use of other oral bisphosphonates, compared to Fosamax?
In addition to alendronate (Fosamax), cases of osteonecrosis of the jaw (ONJ), albeit rare, have been reported in patients taking either risedronate (Actonel®) or ibandronate (Boniva®). Among the class of oral bisphosphonates, more cases have been associated with Fosamax than with Actonel or Boniva. Also, there is no evidence to suggest that the risk of ONJ is less when taking monthly doses of Boniva. Zoledronic acid under the brand name of Reclast® has recently been approved as a once-annual, 15-minute intravenous infusion of a dose of 5 mg to prevent osteoporosis. This dosing was associated with a significant improvement in bone mineral density and bone metabolism markers. It is unknown whether this dosing schedule places the patient at risk for ONJ; however, data does show a higher risk of serious atrial fibrillation in patients receiving Reclast® compared to patients receiving placebo (Black DM, et al, NEJM, 356:1809-22).
4. Will Fosamax or the other oral bisphosphonates continue to be the standard treatment for osteoporosis?
Yes. The oral bisphosphonates continue to be the most effective class of drugs in reducing the risk of osteoporotic fractures and are the first-line therapy in the treatment of osteoporosis. Fosamax has been shown to prevent bone loss at the spine and hip in postmenopausal women, and to reduce fractures by approximately 50%. Risedronate (Actonel) produced a 30% reduction in hip fractures. Fosamax continues to be in the top 50 most widely-prescribed drugs in this country. By 2006, over 190 million prescriptions were dispensed worldwide.
5. Do we know how the jaw bone becomes necrotic from Fosamax?
This question has not been answered and information is only speculative at this time. Osteoporosis can occur due to age-related changes in the number of osteoclasts and bone resorption sites. This overwhelms the production of new bone by osteoblasts and a decrease in bone mass occurs. By inhibiting osteoclastic activity, the oral bisphosphonates seemingly arrest the osteoporotic syndrome. In the process, however, the maxilla and mandible, upon continued exposure to the bisphosphonates, are unable to repair themselves from injury from mechanical forces or invasive surgery such as tooth extraction. This, coupled with a reduction in bone blood supply by the bisphosphonates (antiangiogenic effect), leads to jaw bone necrosis.
6. What are the factors that increase the risk of jaw bone necrosis in Fosamax users?
Patients wih a history of periodontal disease and dental abscesses are at increased risk. Also, dento-alveolar trauma will increase the risk. The use of chronic steroids, such as prednisone, has been identified as a risk factor. Other factors are the duration of exposure and age, with longer treatment regimens and >65 years of age associated with a greater risk of developing the disease. Patients identified with jaw bone necrosis typically were exposed to oral bisphosphonates for 3 years or longer.
7. What are the symptoms that a Fosamax patient would experience which could indicate necrotic jaw bone?
Tooth mobility, mucosal swelling, and/or ulceration. Clinical symptoms would include a nonhealing extraction site, exposed bone surrounded by inflamed soft tissue, and purulent discharge at site of exposed bone. Exposed bone is usually more prevalent in areas such as tori and the mylohyoid ridge.
8. What kind of dental procedures can be performed in Fosamax users with no increase in risk for ONJ?
According to the American Dental Association, all routine procedures can be carried out. Routine dental treatment should not be modified on the basis of oral bisphosphonates on board the patient. However, presence of risk factors such as steroid use, >65 years of age, or prolonged exposure to the oral bisphosphonates may require consultation with an expert in metabolic bone disease prior to routine dental treatment.
9. Is dento-alveolar surgery contraindicated in Fosamax users?
No. According to Ruggiero and Drew (J Dental Research, 2007; 86(11):1013), in asymptomatic patients receiving oral bisphosphonate therapy, dento-alveolar surgery is not contraindicated.
10. Is a so-called “drug holiday” an effective way to reduce the risks of ONJ in Fosamax users prior to dental-alveolar surgery?
A “drug holiday” is a discontinuance of bisphosphonate for a length of time thought to achieve a reduction of risk of ONJ. It is suggested that one consider interrupting bisphosphonate treatment for 3-4 weeks prior to surgery and restarting after bone healing. Based on AAOMS (American Society of Oral and Maxillofacial Surgeons) guidelines, for patients who have taken an oral bisphosphonate for more than 3 years, discontinuation of the oral bisphosphonate for 3 months prior to oral surgery may reduce the risk. The bisphosphonate can be started again once osseous healing has occurred.
For individuals who have taken a bisphosphonate for less than 3 years and have no other risk factors for ONJ, no alteration or delay in the planned surgery is necessary (Ruggiero and Drew).
11. In patients about to begin oral bisphosphonate therapy, should the bisphosphonate be delayed until dental health is optimized?
No. It does not appear necessary for patients to initiate prophylactic dental treatment prior to initiating oral bisphosphonate therapy for osteoporosis. It would be prudent, however, to encourage these patients to maintain optimal dental health .
12. Is diagnostic imaging useful in assessing those bisphosphonate individuals at risk for ONJ?
Imaging modalities have proved helpful in determining the extent of existing necrotic process, but have not been able to demonstrate any efficacy in assessing patients at risk for ONJ. According to the experts, panoramic and periapical radiographs probably will not reveal significant changes in early stages of osteonecrosis and they are poor screening tools for prediction. Computerized tomography (CT) scan also has not proved helpful with early identification of osteonecrosis in asymptomatic patients.