Young Bui
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 ISPHOSPHONATES,
such as pamidronate (Aredia) and zoledronic acid (Zometa), are i.v. drugs
used to reduce bone pain and hypercalcemia of malignancy associated with
metastatic breast cancer, prostate cancer, and multiple myeloma.
(For a table listing all oral and i.v. bisphosphates currently on the market
in the United States, see “Something New
to Consider!” by Doug Kase, in the November?December 2006 issue of
Endo-Mail.) The cancer spreads to the bones, and the growth
of these cancer cells leads to the destruction of bone tissue. This
type of bone damage can cause a lot of pain and fractures. Bisphosphonates
modulate bone turnover and reduce its remodeling when an excessive resorption
occurs. They bind to areas where bone has been destroyed. Their
pharmacological activity is to inhibit osteoclast differentiation and induce
osteoclast apoptosis, resulting in an imbalance in the bone remodeling
process. Oral bisphosphonates, such as aledronate (Fosamax), risodronate
(Actonel), and ibandronate (Boniva), are used for the treatment of postmenopausal
osteoporosis.
Bisphosphonate-associated osteonecrosis (BON)
of the jaw from patients treated with Aredia and Zometa began to appear
in 2003. Most of these cases are associated with dental procedures,
such as tooth extraction. However, there appear to be cases of BON
occurring spontaneously in patients taking these drugs. Several cases
of BON have also been associated with the use of the oral bisphosphonates,
but these patients have been on these medications for a number of years.
Clinical presentation of BON includes pain, swelling
or gum infection, loosening of teeth, drainage, and exposed bone—especially
after a dental procedure. Symptoms may occur spontaneously in the
bone or at the site of a previous dental procedure. Patients may
also experience numbness or a feeling of heaviness in the jaw. BON
may be asymptomatic for weeks or months and only become evident after the
finding of exposed bone in the jaw. The symptoms of BON can mimic
dental or periodontal disease, but routine treatment will not resolve these
symptoms.
Invasive dental procedures should be avoided in
patients receiving i.v. bisphosphonates. Dentists should be aware
that because i.v. bisphosphonates are administered in oncology wards patients
may not acknowledge receiving these drugs when they provide their medical
histories. It is imperative for the dentist to ask patients with
a history of multiple myeloma or metastatic cancer about receiving i.v.
bisphosphonate because these drugs have a long half-life (years).
The following are recommendations for prevention
and treatment of BON in patients on i.v. bisphosphonate therapy, according
to an expert panel from Novartis Pharmaceuticals Corporation (the manufacturer
of Zometa and Aredia).
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Patients should be educated about maintaining excellent oral hygiene to
reduce the risk of infection.
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Dentists should check and adjust removable dentures to avoid soft-tissue
injury.
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Routine dental cleanings should be performed with care so as not to inflict
soft-tissue injury.
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Dental infections should be managed aggressively and, when possible, nonsurgically.
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Endodontic therapy is preferable to extractions; and, when necessary, coronal
amputation with root canal therapy on retained roots to avoid the need
for extraction.
The risk of developing BON in patients on oral
bisphosphonate therapy appears to be very low. When the treatment
plan indicates that the medullary bone or periosteum is going to be involved
in multiple quadrants, the dentist should treat one quadrant or tooth first.
The dentist should allow for a two-month disease-free interval, while treating
the patient with antimicrobials, before treating the other quadrants.
Chlorhexidine should be used two times per day for two months after surgery.
The majority of cases of BON arise within two months of a dental procedure.
With success at the two-month follow-up, treatment may be continued at
a normal pace.
Despite the negative effects of bisphosphonate therapy,
the periodontal literature has suggested that these drugs may be beneficial
in modulating host response for management of periodontal disease.
Guided bone regeneration or guided tissue regeneration should be a concern
because bisphosphonates have been shown to decrease the vascularity of
tissues, which may have a negative effect on grafted sites. At this
time, there are limited data regarding the effects of implant placement
in patients taking oral bisphosphonates. Treatment plans should be
considered carefully, since implant placement requires the preparation
of the osteotomy site.
If extractions or bone surgery are necessary,
conservative surgical technique with primary tissue closure should be considered,
when possible. In addition, immediately before and after surgical
procedures involving bone, the patient should rinse gently with a rinse
containing chlorhexidine. Chlorhexidine should be used two times
per day for two months after surgery. Recent studies have shown that
osteoclastic function returns after patients go off oral bisphosphonates
for about five months. This is the best time to do any type of surgery
if the patient can wait that long.
Conventional non-surgical endodontic treatment
is preferred if the tooth is salvageable. It is not good to instrument
beyond the apex, so an apex locator is highly recommended. If surgical
endodontic procedures are required, follow the guidelines described above
for any oral and maxillofacial surgical procedure.
All routine restorative procedures can be done in the usual manner.
All prosthodontic appliances should be adjusted for fit as needed.
January - March 2007
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The
risk of developing BON in patients on oral bisphosphonate therapy appears
to be very low.
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