Oral Bisphosphonates and Optimal Oral Health
Samia Hardan, DDS
Bisphosphonates are widely used for the treatment of
osteoporosis, hypercalcemia of malignancy, osteolytic lesions of multiple
myeloma, and bone metastasis of solid tumors. The association between osteonecrosis
of the jaw (ONJ) and the use of bisphosphonates in compromised patients has
been established in the literature.1-10 By suppressing osteoclasts,
bisphosphonate drug mechanisms increase overall bone mass.8 In
osteoporosis, it inhibits osteoclast-mediated bone resorption, which reduces
the gradual reduction of bone mass with aging.2,3,8,9 This effect, however, may carry a potential
for severe suppression of bone turnover, which may impair wound healing and
reparative properties. Although the exact mechanism of bisphosphonate-related
osteonecrosis (BRONJ) has not been determined, in most cases, the pathogenesis
is consistent with a suppression of bone physiologic remodeling and wound
healing. The profound inhibition of osteoclast function also can inhibit normal
bone turnover to an extent that local microdamage from normal mechanical
loading or an injury cannot be repaired.10
understanding of the various manifestations of BRONJ is critical to prevention,
early recognition, and treatment. The clinical presentation of BRONJ is
variable, ranging from asymptomatic soft tissue swelling to painful exposed
necrotic bone and infection. The majority of patients present with an area of
exposed bone—with or without pain—in the mandible alone (ie, 68.1%), in the
maxilla (ie, 27.7%), or, less commonly, in both (ie, 4.2%).8 Mobile teeth, cutaneous fistula, mucosal fistula, or bone
exposed through the skin are less frequent.1 Some patients may have
more subtle complaints (eg, feelings of heaviness in the jaw, numbness).
Imaging and Laboratory Examination
evaluation is not particularly effective during the early stages of the disease.
Periapical and panoramic radiographs may, however, be of assistance in ruling
out other causes of dental pain, as well as metastatic lesions. The most common
findings are hyperostotic lamina dura and widened periodontal ligament.1
C-terminal cross-linked telopeptide (CTx) test has been used in metabolic
studies as an indicator of the rate of bone renewal. Serum CTx values < 100
pg/ml have been associated with a high risk of developing BRONJ, values of 100
to 150 pg/dl have been associated with a moderate risk, and values > 150
pg/dl generally indicate a minimal risk (11). The CTx test, however, measures
primarily metabolism of trabecular bone and not cortical bone, and is
representative of skeletal bone in general. Therefore, this test may not be
reflective of the cortical plate of bone which supports the dentition.
the diagnosis and careful evaluation of the extent and severity of bone
involvement are paramount in the management of patients and prognosis of BRONJ.
While the American Association of Oral and Maxillofacial Surgeons (AAOMS)
established a working definition for BRONJ, Wade and Suzuki subsequently established
a modification of the AAOMS-proposed staging system to include treatment
strategies using the CTx serum test.1
be deferred when patients are generally asymptomatic and are receiving IV
bisposphonates (stage 0iv) or have been taking oral bisposphonates for more
than three years (stage 0or), until serum CTx levels are obtained. Ctx levels
> 150 pg/ml indicate that odontoalveolar surgery is relatively safe. For
patients with serum level < 150 pg/dL, the prescribing physician should be
contacted regarding withdrawal of bisphosphonate therapy for a period of three
months if possible. If repeated CTx levels are > 150 pg/dl, dental treatment
may be rendered. Otherwise, the period is extended in three month intervals
until levels are > 150pg/dl. If emergency treatment must be performed, CTx
levels should be obtained as soon as possible, and the physician should be
present with asymptomatic exposed bone, a detailed oral examination and
noninvasive treatment plan should be undertaken. The patient should be educated
regarding the exposed bone, instructed in proper oral hygiene of the area, and
placed on a maintenance regimen of chlorhexidine oral rinses. Frequent
follow-up visits should be implemented, including close monitoring for any
signs of soft or hard tissue infection or additional exposed bone. A baseline
CTx level should be obtained, and the treating physician should be contacted to
investigate the possibility of temporarily discontinuing bisphosphonate
present with exposed bone, pain, and soft tissue or bone infections, they
should have cultures taken to determine appropriate antibiotic treatment.
Empiric therapy is recommended if results are inconclusive. The standard
regimen is penicillin V potassium 500 mg every six hours and an oral rinse
using chlorhexidine 0.12% twice daily. In refractory cases, metronidazole 500
mg every six hours is added for seven to 10 days. For patients who are allergic
to penicillin, levofloxacin 500 mg daily has proven to be an excellent
alternative. A baseline CTx level should be obtained, and more extensive treatment
may proceed when the level exceeds 150 pg/dl. Empiric data, however, does not indicate
that increasing CTx level will result in reduction of BRONJ risk.
present with all of the preceding signs and symptoms and at least one of the following:
pathologic fracture, extraoral fistula, or osteolysis extending to the inferior
border. In these patients, more conservative treatment methods may have already
failed. Therefore, to alleviate pain and eliminate infection, it may be
necessary to debride or resect large areas of bone. This approach has met with
some success. To date, however, no standardized treatment protocols exist.
of treatment is limited, prevention of BRONJ is very important and begins with
identifying patients at increased risk.12,13 These include patients
with a history of dentoalveolar trauma and those with prolonged exposure to
bisphosphonate therapy.10 In the majority of BIONJ reported cases to
date, recent dentoalveolar trauma was the most prevalent and consistent risk
factor. Patients with inflammatory dental diseases (eg, periodontal disease,
dental abscesses) are at seven-fold increased risk for developing BRONJ. This
underscores the importance of maintaining good oral health and avoiding
extractions, especially in high-risk patients such as women and men with
prolonged (ie, more than three years) exposure and those with concomitant
bisphosphonate therapy is the first-line treatment option for patients who
require osteoporosis treatment and is highly effective in preventing fractures.
Although a definitive causal relationship between the use of oral
bisphosphonate and ONJ has yet to be established, the potential risk of bone
necrosis and associated morbidity cannot be ignored. Prevention is superior to
treatment, and the establishment of meticulous oral hygiene is important to
prevent pathology necessitating surgical management.
the Department of Periodontology and Oral Implantology, Temple University, Kornberg
School of Dentistry, Philadelphia, Pennsylvania.
Microbiology and Immunology, School of Medicine; Professor of Periodontology
and Oral Implantology, Department of Periodontology and Oral Implantology,
Temple University, School of Dentistry; Associate Dean for Graduate Education
and International Affairs and Program Director of Graduate Periodontics, Temple
University, Philadelphia, Pennsylvania.
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