Case Report/Clinical Techniques
Endodontic Implications of Bisphosphonate-Associated
Osteonecrosis of the Jaws: A Report of Three Cases
Harmon Katz, DDS
Abstract
Bisphosphonates are commonly used in medicine to
maintain bone density in patients with certain nonneo-
plastic diseases or cancers. A serious adverse effect of
bisphosphonates that has substantial dental signifi-
cance is osteonecrosis that appears to uniquely affect
the mandible and maxilla without occurring in other
bones of the skeleton. Patients with bisphosphonate
associated osteonecrosis of the jaws may present with
pain and exposed necrotic bone. This has substantial
clinical implications because surgical procedures (in-
cluding extractions or endodontic surgical procedures)
are contraindicated in the jaws of these patients and
the presenting pain may mimic pain of odontogenic
origin. This report describes three patients with
bisphosphonate associated osteonecrosis and empha-
sizes the endodontic implications of managing these
patients.
Key Words
Bisphosphonates, osteonecrosis
From the Robert Wood Johnson University Hospital, New
Brunswick, New Jersey.
Address requests for reprint to Dr. Harmon Katz, 76 Liv-
ingston Ave, New Brunswick, NJ 08901. E-mail address:
docendo1@aol.com.
Copyright © 2005 by the American Association of
Endodontists
JOE — Volume 31, Number 11, November 2005
T he bisphosphonates have a primary indication of inhibiting bone resorption and
thereby maintaining bone density (1, 2). This class of drugs is based on a common
chemical structure (pyrophosphate analogs) and, as indicated in Table 1, is identified
by a common ending in their generic names (“ dronate”). These drugs can
be subdivided into the nitrogen-containing bisphosphonates and the nonnitrogen
bisphosphonates (3). Bisphosphonates are commonly used in medicine with nearly 21
million prescriptions issued for alendronate in the United States alone in 2004. This
class of drugs is often indicated for the maintenance of bone density in patients with
nonneoplastic diseases (e.g. osteoporosis, ankylosing spondylitis, corticosteroid-in-
duced bone loss, and Paget’s disease) and certain cancers (e.g. neoplastic hypercal-
cemia, multiple myeloma, and bone metastases secondary to breast and prostate can-
cer) (3–5). Their mechanism(s) of action are not completely known, but in general
they are thought to act by inhibiting osteoclastic bone resorption, by exerting an anti-
tumor effect, by reducing angiogenesis, and possibly other effects (2, 3, 6, 7). However,
several adverse effects have been reported with bisphosphonates. This includes renal
toxicity, fever, bone pain, hypocalcemia, and mild GI complaints (2, 5, 8 –10).
A serious adverse effect of bisphosphonates that has substantial dental implica-
tions is osteonecrosis of the jaws; other bones in the skeleton do not appear to be
involved (11). Several case reports, letters to the editor, and reviews have documented
patients developing osteonecrosis of the jaws after bisphosphonate administration (12–
30). Bisphosphonate associated osteonecrosis has substantial clinical implications be-
cause many of these patients fail to heal after dental surgical procedures (e.g. extrac-
tion) and in many cases the postsurgical defect has been reported to be larger than the
preoperative defect (25). Because there is little information available about endodontic
implications of bisphosphonate associated osteonecrosis, there is a need to describe the
impact on endodontic treatment.
The following three cases presented to a private practice in endodontics in a major
metropolitan area and thus may represent a patient population that similar to those
observed in private practices in other major metropolitan areas.
Case 1
A 52-yr-old African-American physician presented with a chief complaint of severe
pain diffusely radiating throughout the right mandibular and maxillary posterior re-
gions. The pain started 2 weeks before his appointment and was spontaneous in nature
and sporadic in occurrence. It was not altered by mastication or thermal stimuli. A
review of the medical history was significant for multiple myeloma. The myeloma was
diagnosed 6 yr ago and treated with standard chemotherapy. Bisphosphonate treatment
started 18 months ago and consisted of monthly intravenous (i.v.) injections of 4 mg
zolendronate (Zometa). The Zometa treatment was stopped 3 months before this ex-
amination in an attempt to prevent osteonecrosis. A review of the dental history indi-
cated that tooth #31 was extracted 3 months ago. The clinical examination revealed a
draining extraction site in the #31 region with bone sequestration (Fig. 1). The maxil-
lary teeth presented with abrasion. All maxillary and mandibular teeth tested within
normal limits for pulpal vitality testing (thermal and electrical) with no sensitivity to
palpation or percussion or signs of periodontal pocketing greater than 4 to 5 mm. The
pain was diagnosed as nonodontogenic in origin and the patient was referred back to his
oral surgeon. A follow-up consultation with the oral surgeon indicated a diagnosis of
osteonecrosis in the region of the extraction site. Subsequent treatment consisted of
antibiotic and re-curretage of the extraction socket without improvement. The patient is
Bisphosphonate-Associated Osteonecrosis 831
Case Report/Clinical Techniques
TABLE 1. Examples of bisphosphonates
Subclass of Route of
Generic Name Trade Name
Bisphosphonate Administration
Nitrogen containing Zolendronate (Zoledronic acid) Zometa IV
Nitrogen containing Pamidronate Aredia Oral & IV
Nitrogen containing Alendronate Fosamax Oral
Nitrogen containing Ibandronate Boniva Oral & IV
Nitrogen containing Risedronate Actonel Oral
Non-Nitrogen Tiludronate Skelid Oral
Non-Nitrogen Clodronate Bonefos, Ostec Oral
Non-Nitrogen Etidronate Didronel Oral

Figure 1. Maxillary and mandibular preoperative radiographs of patient #1. (A,

B) Periapical radiograph of the right mandibular and maxillary regions. (C)
Clinical photograph of nonhealed extraction site of #31 at time of examination.

maintained on palliative treatment consisting of local wound dressings,

antibiotics, and antimicrobial rinses. The administration of ibuprofen
800-mg produced some pain relief.

Case 2
A 60-yr-old Caucasian female presented with a chief complaint of
pain restricted to the maxillary right second molar region. The pain had
started 3 days before her appointment and became severe during mas-
tication or after application of cold; heat did not alter the pain. A review
of the medical history was significant for a history of multiple myeloma.
The myeloma was diagnosed 6 yr ago and treated with chemotherapy.
The initial bisphosphonate treatment was pamidronate (Aredia) for 1 yr
followed by 1 yr of monthly i.v. injections of 4 mg zolendronate (Zo-
meta). A review of the dental history indicated a history of a bone graft
procedure in the region of teeth #2–3 approximately 10 months ago
(Fig. 2A). Radiographic examination revealed prior nonsurgical root
canal treatment of tooth #3 with periradicular surgery consisting of
mesiobuccal root-end preparation with filling with an alloy, without
signs of periradicular pathosis (Fig. 2A). Tooth #2 was positive for
pulpal vitality testing and this reproduced the severe pain to cold. No
mobility was observed, but tooth #2 elicited severe pain upon mild
percussion. The clinical examination revealed a 10 mm ⫻ 7 mm area of
Figure 2. (A) Radiograph before periodontal surgery. (B, C) Preoperative and
postendodontic radiographs. (D) Clinical photograph of case #2.
exposed bone in the palate adjacent to teeth #2– 4 (Fig. 2B). The pain
was diagnosed as irreversible pulpitis with acute apical periodontitis
and originating from tooth #2 (Fig. 2C). The patient was informed that
the palatal bone exposure likely contributed to the pain, but that no
further periodontal surgical or extraction treatments should be indi-
cated given the history. Instead, the nonsurgical treatment of tooth #2
was deemed to be a conservative means of reducing at least a portion of
the factors contributing to the patient’s pain. The patient received local
anesthesia consisting of 4 ml of 2% lidocaine with 1:100,000 epineph-
rine administered by posterior superior alveolar nerve block injection
and palatal infiltration. Tooth #2 was isolated, accessed, cleaned, and
shaped using the crown down method with Profiles. The canal systems

832 Katz JOE — Volume 31, Number 11, November 2005


Figure 3. Preoperative and postendodontic radiographs of patient #3.
were obturated by cold lateral compaction of Resilon and the tooth was
temporized (Fig. 2D). The patient became comfortable by 2 days after
endodontic therapy.
Case 3
A 72-yr-old Caucasian male presented with a chief complaint of
pain restricted to the maxillary right second molar region. The pain had
started 7 days before his appointment and was increased by cold, but
not altered by heat or mastication. A review of the medical history was
significant for a history of prostate cancer with bone metastasis, cardiac
insufficiency, and pulmonary edema. The prostate cancer was diag-
nosed 1 yr ago and treated with chemotherapy. Bisphosphonate treat-
ment consisted of 1 yr of monthly i.v. injections of 5 mg zolendronate
(Zometa). The dental history was remarkable for a prior occurrence of
osteonecrosis after the extraction of the maxillary left second molar; this
region was not painful at the time of examination. The clinical exami-
nation revealed tooth #3 had extreme sensitivity to cold with a lingering
duration after application of the stimulus. The tooth was diagnosed as
having irreversible pulpitis with normal periradicular tissue. Extensive
coronal caries indicated a poor prognosis for tooth #3 and a carious
lesion was also found on tooth #2 (Fig. 3A). Consultation with the
patient’s oral surgeon and oncologist supported a conservative dental
treatment plan consisting of nonsurgical endodontic treatment of tooth
#3. A surgical procedure (extraction) was believed to impose consid-
erable risk for the development of osteonecrosis. The patient provided
informed consent for this treatment. The patient received local anesthe-
sia consisting of 1.8 ml of 4% articaine with 1:100,000 epinephrine by
infiltration injection. Tooth #3 was isolated, accessed, cleaned, and
shaped using the step back method with Profiles. The canal systems
were obturated by cold lateral compaction of Resilon and the tooth was
temporized (Fig. 3B). Tooth #2 had excavation of caries with a tempo-
rary filling. The patient became comfortable immediately after end-
odontic therapy and has remained without symptoms at a 6-month
follow-up.
Discussion
These cases illustrate the endodontic implications of treating pa-
tients with a history of bisphosphonate administration. The major con-
clusions drawn from these cases are that: (a) collection of a careful
medical history and recognition of drug class is essential for detection of
patients at risk; (b) preventive dental treatments including nonsurgical
endodontic therapy must be considered instead of surgical options (in-
cluding extractions or surgical endodontic treatment) and ideally
should be started before bisphosphonate therapy (31); and (c) pain
related to osteonecrosis may mimic pain of odontogenic origin and
should be considered in the differential diagnosis.
JOE — Volume 31, Number 11, November 2005
Case Report/Clinical Techniques
Interestingly, most case reports describe osteonecrosis with the
nitrogen-containing bisphosphonate class of drugs (e.g. zolendronate,
pamidronate) rather than the less potent nonnitrogen containing
bisphosphonates (30). In one survey, patients treated with zolendr-
onate had more than twice as many cases of osteonecrosis as compared
to patients treated with pamidronate (10% versus 4%; p ⬍ 0.005) (14).
Although it has been observed that case reports do not prove a cause-
and-effect relationship (31, 32), it should be noted that the FDA has
issued an advisory about bisphosphonates as a risk factor for osteone-
crosis of the jaws (33). Unfortunately, some recent reports have evalu-
ated the proposed use of bisphosphonates as an adjunctive treatment for
increasing healing success with dental implants or periodontal treat-
ment (34 –37). However, an evaluation of the potential adverse effects
of these drugs cannot support this proposal.
Common clinical features in case reports of bisphosphonate asso-
ciated osteonecrosis include: (a) prior history of bisphosphonate ad-
ministration; (b) concurrent dental procedures or pathoses (e.g. ex-
tractions, dental infections, etc); (c) other drugs (e.g. glucocorticoids,
thalidomide); and (d) systemic disorders (e.g. diabetes, renal impair-
ment, peripheral vascular disease) (12–14, 18, 22, 38). The osteone-
crosis is often related to a site of previous dental treatment (e.g. an
extraction), but can occur in regions without prior dental treatment
and, in these cases, the lingual surface of the posterior mandible is
frequently involved (11). Patients often present complaining of jaw pain
that can be localized or diffuse (mandible more often than maxilla),
with some studies reporting an average of two areas of exposed bone
per patient (15, 22, 23, 30, 39). An infection secondary to bone expo-
sure is a common finding (39). It is not known whether some bisphos-
phonates have a reduced risk of being associated with osteonecrosis, or
whether variations in dosage or duration of treatment alter the risk. This
is clearly an area of future research.
The mechanisms for bisphosphonate associated osteonecrosis are
unclear, but have impact on the management of these patients. Bisphos-
phonates tightly bind to hydroxyapatite and are incorporated into the
growing skeleton (1). Accordingly, the half-life of this drug in bone has
been estimated to be greater than 10 yr. Because bisphosphonates are
typically administered over extended periods of time (months-years),
surgical procedures are thought to simply expose more of the drug
previously incorporated into bone. Thus, surgical resection of an area of
osteonecrosis or a dental surgical procedure (extraction, endodontic,
or periodontal surgery, etc.) are not likely to resolve the problem.
The treatment for osteonecrosis of the jaws is problematic because
surgical resection of the necrotic area does not appear to eliminate the
osteonecrotic process (14, 39). In addition, hyperbaric oxygen therapy
or extensive antibiotic treatment does not appear to promote healing in
these cases (39). Instructing patients to stop taking bisphosphonates
has been reported to have little if any effect on the progression of
osteonecrosis (25, 39). This might be due in part to the very long
half-life of the drug in bone and to its resistance to metabolic degrada-
tion (2, 25).
Case reports on endodontic implications of bisphosphonate asso-
ciated osteonecrosis of the jaws should serve to inform the clinician
about the diagnostic and therapeutic implications of this important ad-
verse effect (40). As a first approximation, many of the management
recommendations are similar to those used for the head and neck
cancer patient with a risk for osteoradionecrosis. In particular, recog-
nition of patient risk factors before treatment is essential. Early consul-
tation with the patient’s oncologist is important because preventive den-
tal care, ideally before bisphosphonate treatment, will likely reduce the
risk of subsequent osteonecrosis (41). Patients should be informed of
an increased potential risk for osteonecrosis and the importance of
conservative therapy. This is an important issue since comparatively few
Bisphosphonate-Associated Osteonecrosis 833
Case Report/Clinical Techniques
studies have discussed the prognostic impact of drugs on the outcome
endodontic therapy. If patients are seen after bisphosphonate treatment,
then preventive oral healthcare combined with nonsurgical dental pro-
cedures should be considered and consultation with an oral and max-
illofacial surgeon may be warranted. Preventive measures including
fluoride and possibly 0.12% chlorhexidine may be considered to re-
duce the potential for tooth extractions because of caries or periodontal
conditions. Nonsurgical endodontic treatment (or retreatment) should
be considered as the alternative to extraction or surgical endodontic
treatment. If endodontic treatment is indicated, then procedures mini-
mizing trauma to the marginal (e.g. rubber dam clamp position) and
apical (e.g. length of instrumentation and obturation) periodontal tis-
sues should be considered. Pain control is important in these patients
because pain is often a primary symptom prompting patients to seek
health care. No controlled clinical trials exist to predict optimal anal-
gesics for these patients and consultation with the patient’s oncologist
may be an important consideration.
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