Documente Academic
Documente Profesional
Documente Cultură
© 2008 American Dental Association. The sponsor and its products are not endorsed by the ADA.
A S S O C I A T I O N R E P O R T
ackground. Reports of
in a person taking
ibandronate (Boniva, Roche Pharmaceuticals, panel to develop guidance for dentists treating
Basel, Switzerland), according to Roche (J. these patients.
Travis, oral communication, March 2006). For Incorporating expert panel recommenda-
alendronate (the most commonly prescribed oral tions into clinical decision making. The den-
bisphosphonate), this translates into a sponta- tist, knowing the patient’s health history and vul-
neous BON incidence (or rate at which new cases nerability to oral disease, is in the best position to
occur) of approximately 0.7 cases per one hun- make treatment recommendations in the interest
dred thousand person-years’ exposure. To date, a of each patient. For this reason, expert panel rec-
true cause-and-effect relationship between ommendations are intended to provide guidance,
osteonecrosis of the jaw and bisphosphonate use and are not a standard of care, requirements or
has not been established. Table 1 lists all oral regulations based on scientific evidence. The rec-
and IV bisphosphonates on the market in the ommendations are a resource for dentists to use
United States. in their practice, in addition to the dentist’s own
The limited data on reported cases have not professional judgment, the information available
allowed for identification of other risk factors for in the dental and medical literature, and informa-
developing this complication. Extrapolating from tion from the patient’s treating physician. The
cases described in oncology patients receiving IV recommendations must be balanced with the
bisphosphonate therapy, it might be possible that practitioner’s professional judgment and the indi-
using oral glucocorticoids for chronic conditions5,6 vidual patient’s preferences and needs.
and estrogen6 may increase the risk of developing Through the development of expert panel rec-
BON. In cancer patients receiving IV bisphospho- ommendations, areas for which there is little evi-
nate therapy, the median time from starting dence were identified. To address these gaps in
therapy to developing BON was 25 months.7 In the evidence, topics for future research are
addition, being older (over 65 years) also may included in this document.
increase the risk.7,8 The most common dental Expert panel. Panelists were selected on the
comorbidity in these patients reportedly is clini- basis of their expertise in the relevant subject
cally and radiographically apparent periodontitis.5 matter and on their respective dental or medical
In light of the uncertainty surrounding the specialty. Panelists were required to sign a disclo-
incidence of BON and concomitant risk factors, sure stating that neither the panelist nor his or
dentists have questioned how to manage the care her spouse or dependent children had a signifi-
of patients receiving oral bisphosphonate cant financial interest that would reasonably
therapy. The American Dental Association appear to affect the development of these
Council on Scientific Affairs assembled an expert recommendations.
for weeks or months, and may become evident tions are based on expert opinion only. Dentists
only after the finding of exposed bone in the jaw are encouraged to check “www.ada.org/prof/
during a routine examination. In some cases, the resources/topics/osteonecrosis.asp” before treating
symptoms of BON can mimic dental or peri- patients who are taking oral bisphosphonates, as
odontal disease. Routine dental and periodontal these recommendations will be updated as new
treatment will not resolve these symptoms. In information becomes available.
this case, if the patient is receiving bisphospho- General recommendations. As with all
nate therapy, BON must be considered as a pos- dental patients, routine dental examinations are
sible diagnosis, even in the absence of exposed recommended.
bone. If BON is suspected, dentists are encour- A comprehensive oral evaluation should be car-
aged to contact the FDA’s MedWatch program ried out of all patients about to begin therapy
at “www.fda.gov/MedWatch/report.htm” or with oral bisphosphonates (or as soon as possible
1-800-FDA-1088. after beginning therapy).
The dentist should inform the patient taking
PANEL CONCLUSIONS oral bisphosphonates that
On the basis of a literature review and of expert dthere is a very low risk (estimated at 0.7 cases
opinion, the panel made the following conclusions per 100,000 person-years’ exposure) of developing
implications of oral bisphosphonate therapy and Despite the untoward effects of bisphosphonate
the risk of BON. The patient should understand therapy, the periodontal literature has suggested
that at this time, the risk of developing that these drugs may be beneficial in modulating
osteonecrosis of the jaw is considered very small, host response for management of periodontal dis-
and that the vast majority of patients taking an eases.24,25 As such, patients with destructive peri-
oral bisphosphonate do not develop any oral odontal diseases who are receiving oral bisphos-
complications. phonate therapy should receive appropriate forms
When the treatment plan dictates that the of nonsurgical therapy, which should be combined
medullary bone and/or periosteum is going to be with a prolonged phase of initial therapy for
involved in multiple sextants, the dentist should observation. If the disease does not resolve, sur-
treat one sextant or tooth first, if dentally pos- gical treatment should be aimed primarily at
sible. At that point, the dentist should allow for a obtaining access to root surfaces, with modest
two-month disease-free follow-up, treating the bone recontouring being considered when neces-
patient with antimicrobials, before other sextants sary. Without further data, guided bone regenera-
are treated with similar therapy. (Note: Typically, tion or guided tissue regeneration should be judi-
chlorhexidine is used two times per day for two ciously considered, in view of the fact that
months after surgery. On the basis of the experi- bisphosphonates have been shown to decrease the
to discover the molecular mechanisms that lead to bone: an emerging oral complication of supportive cancer therapy.
Cancer 2005;104(1):83-93.
the formation of BON and the role of bisphospho- 5. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-
nates in the alteration of bone remodeling and its induced exposed bone (osteonerosis/osteopetrosis) of the jaws: risk fac-
tors, recognition, prevention, and treatment. J Oral Maxillofac Surg
effect on BON. Research on the pharmacogenetics 2005;63:1567-75.
that place patients at risk of developing BON may 6. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak
CY. Severely suppressed bone turnover: a potential complication of
be helpful for the detection of patients at alendronate therapy. J Clin Endocrinol Metabolism 2005;90:1294-301.
increased risk. 7. Bagan JV, Jimenez Y, Murillo J, et al. Jaw osteonecrosis asso-
ciated with bisphosphonates: multiple exposed areas and its relation-
Clinical research. Research in the following ship to teeth extractions—study of 20 cases. Oral Oncol 2006;42:327-9.
clinical areas is needed: 8. Markiewicz MR, Margarone JE, Campbell JH, Aguirre A.
Bisphosphonate-associated osteonecrosis of the jaws: a review of cur-
dactive pharmacovigilance regarding patients rent knowledge. JADA 2005;136:1669-74.
currently taking bisphosphonates, as BON is a 9. U.S. Food and Drug Administration. MedWatch 2005 safety alerts.
Available at: “www.fda.gov/medwatch/SAFETY/2005/
relatively rare adverse event and randomized safety05.htm#zometa2”. Accessed March 27, 2006.
clinical trials may not have the power or the 10. Ezra A, Golomb G. Administration routes and delivery systems of
bisphosphonates for the treatment of bone resorption. Adv Drug Deliv
necessary duration to detect rare adverse drug Rev 2000;42:175-95.
reactions; 11. Berenson JR, Rosen L, Vescio R, et al. Pharmacokinetics of
pamidronate disodium in patients with cancer with normal or impaired
doutcomes of routine dental therapy in patients renal function. J Clin Pharmacol 1997;37:285-90.
taking oral bisphosphonates; 12. Ruggiero S, Gralow J, Marx RE, et al. Practical guidelines for the