Summary Osteonecrosis of the jaw is a disease which needs to be taken into account whenever there is exposure of bone as a secondary result of any dental operation in a patient who has been taking biphosphonates over a long period of time. Unknown until the last few years, knowledge of such a pathology has increased due to the current increase in the taking of biphosphonates in the population, with most of the published cases being related to the taking of biphosphonates intravenously. We present 5 clinical cases of osteonecrosis of the jaw associated with the use of oral biphosphonates

AB Marín Fernández

Arjona Giménez C

Dios Navarrete

CiteSeerX

37
CLINICAL NOTE / Rev Osteoporos Metab Miner 2012 4;1:37-41
Marín Fernández AB1, Arjona Giménez C2, de Dios Navarrete J2
1 Servicio de Cirugía Oral y Maxilofacial - H. U. Virgen de las Nieves - Granada. Xanit Hospital Internacional - Benalmádena - Málaga
2 Servicio de Cirugía Ortopédica y Traumatología - H. U. Virgen de las Nieves - Granada
Osteonecrosis of the jaw associated
with the use of oral biphosphonates: 
apropos five cases
Correspondence: Ana Belén Marín Fernández - Calle Unis, 14 - Otura - 18630 Granada (Spain)
e-mail: anita1981@msn.com 
Date of receipt: 02/01/2012
Date of acceptance: 27/01/2012
Summary
Osteonecrosis of the jaw is a disease which needs to be taken into account whenever there is exposure
of bone as a secondary result of any dental operation in a patient who has been taking biphosphonates
over a long period of time. Unknown until the last few years, knowledge of such a pathology has incre-
ased due to the current increase in the taking of biphosphonates in the population, with most of the
published cases being related to the taking of biphosphonates intravenously. We present 5 clinical cases
of osteonecrosis of the jaw associated with the use of oral biphosphonates.
Key words: osteonecrosis of the jaw, biphosphonates, alendronate, ibandronate.
38
CLINICAL NOTE / Rev Osteoporos Metab Miner 2012 4;1:37-41
Introduction
Osteonecrosis of the jaw (ONJ) is characterised by
an ulcerated lesion in the oral mucosa with expo-
sure of bone for a period of longer than 8 seeks,
located in the jaw and associated with the use of
oral and intravenous biphosphonates in the
absence of cervicofacial radiotherapy1-3.
Since 2003, with the appearance of the first cli-
nical cases of ONJ in the literature, there have
been numerous publications regarding the deve-
lopment of this pathology4-6, the majority of these
secondary to therapies with intravenous biphos-
phonates, associated, in turn, with different che-
motherapy and radiotherapy treatments.
In this article we bring together a series of 5
cases of ONJ related to the taking of oral biphos-
phonates, and carry out a bibliographic review of
the pathology and management of the patient
taking oral biphosphonates who is going to under-
go oral surgery.
Clinical cases
We present 5 cases of ONJ in relation to the use
of oral biphosphonates seen in our service during
the years between 2005 and 2008 (Table 1). They
all have as common antecedents dental surgery
and the taking of oral biphosphonates at the time
of the diagnosis of ONJ.
Case number 1. Woman of 70 years of age
diagnosed with early osteoporosis due to an ear-
lier hysterectomy which was treated with ibandro-
nic acid over a period of 4 years. She developed a
clinical picture characterised by pain and tumefac-
tion in the submaxillary cells and inferior vestibu-
le compatible with grade III ONJ. She was treated
surgically by the elimination of the sequester,
curettage and local advancement flaps to close the
lesion, associated with intravenous antibiotic treat-
ment with amoxicillin clavulanate 1g/200 mg
every 8 hours for two week, plus 100 mg of
doxycycline orally every 24 hours for 14 further
days (Figures 1 & 2).
Case number 2. Patient with history of arthro-
sis of the knee (with knee prosthesis) recurrent
polychondritis in treatment with corticoids and
type II, or senile osteoporosis. The patient had
received alendronate orally over a period of 4
years, developing grade II ONJ. She was subse-
quently treated with intravenous antibiotherapy
consisting of amoxicillin clavulanate 1g/200 mg
every 8 hours for a total of three weeks 
Cases number 3, 4 and 5. The last three
patients were women diagnosed with senile oste-
oporosis (one of them with history of rheumatoid
arthritis treated with corticoids and immunosup-
pressants) and treated with oral alendronate (for
three, five and four years, respectively), who
developed ONJ grade III. They were treated by
curettage of the lesion combined with intravenous
antibiotherapy using amoxicillin clavulanate
1g/200 mg every 8 hours for a minimum period of
2 weeks.
All the patients had a complete remission of
the lesions.
Discussion
ONJ was defined as such in the year 2007 by the
American Society for Bone Mineral Research
(ASBMR)1 as an entity characterised by three requi-
rements: previous taking of biphosphonates, pre-
sence of exposed or necrotic bone in the maxillary
region which has been developing or more than 8
weeks, and the absence of radiotherapy in this area.
Traditionally, ONJ has been related to the use
of intravenous biphosphonates in patients with
history of neoplasms with metastasis, its secondary
appearance related to the use of oral biphospho-
nates being rare. In the last few years, the growth
in the use of oral biphosphonates in the treatment
of osteoporosis has increased the number of cases
of ONJ described7. In certain pathologies, such as
rheumatoid arthritis, in which the development of
serious osteoporosis has necessitated the initiation
of treatment with oral biphosphonates, the appea-
rance of ONJ has also been observed8. It has been
determined that the risk of ONJ due to oral
biphosphonates is related to the duration of treat-
ment (above all, if it is greater than 3 years)9. In
the cases described in this clinical note a period of
approximately 3 or more years of treatment with
biphosphonates was observed before the appea-
rance of ONJ.
Within the group of biphosphonates associated
with the development of ONJ, zoledronic acid is
that which has resulted in most cases of ONJ10,11.
Woo et al.6, in a systematic review of 368 cases of
ONJ observed that the oral biphosphonate which
most frequently produced ONJ was alendronate,
which agrees with our review. If we compare oral
biphosphonates with intravenous it is seen that
the intravenous administration develops ONJ more
rapidly. Lazarovici et al., in 201111 studied 27
patients who had ONJ concluding that the avera-
ge time for its appearance was 60 months for
those who had taken alendronate, 13 for zoledro-
nic acid and 35 months for pamidronate.
Etiopathogenically, there is a series of factors
which may explain the development of ONJ2.
These are: changes in immunity and the neoplasm
repair mechanisms, vascular compromise (in the
same way as happens in other areas such as the
hip and half-moon bone, essentially), low bone
turnover, and toxicity in the bone12 and other soft
tissues of the biphosphonates themselves13.
ONJ is characterised clinically by areas of
exposed bone accompanied by fistulation, pain,
paresthesia, dental movement, and even fracture
of the jaw. In 65% of cases we find mandibular
affectation, in 25%, affectation of the upper jaw
and in approximately 10% bimaxillary affectation6.
In most cases the prognosis is favourable, with
ONJ due to oral biphosphonates having a better
prognosis than those cases caused by intravenous
biphosphonates11. The latter is aggravated by the
deteriorated physical state of these patients (previous
treatment with chemotherapy and/or radiotherapy).
The treatment for ONJ is based on the grade of
ONJ which is diagnosed5 (Table 2). In ONJ grade
I the treatment of choice is rinsing with 0.12%
39
CLINICAL NOTE / Rev Osteoporos Metab Miner 2012 4;1:37-41
chlorhexidine; in grade II the first treatment needs
to be associated with oral or intravenous antibio-
therapy; and finally, in grade III, to those measu-
res already mentioned should be added surgical
treatment.
Therefore, the most important thing is to deci-
de on how to manage the patient who is submit-
ted for mouth surgery and who is being treated
with oral biphosphonates over a long period of
time. For De Souza et al.14 it was necessary to pos-
tpone surgery and refer the patient to a specialist
(rheumatologist or traumatologist) to evaluate the
suspension of the biphosphonate and, even to
substitute it for another medicine for the treatment
of osteoporosis before surgery.
On the other hand, the American Society, in
2009, developed a protocol for the management of
patients taking oral biphosphonates and who
require a surgical intervention which involves the
manipulation of the maxillary bones9: 
- In patients whose treatment with oral biphos-
phonates has lasted less than 3 years and with no
risk factors, it is not necessary to  take any special
measures. 
- In patients whose treatment with oral biphos-
phonates has lasted for less than 3 years  and who
are taking corticoids concurrently it would be
necessary to stop the oral biphosphonate treat-
ment at least 3 months before surgery, if the syste-
mic conditions of the patients allow it. The oral
biphosphonates may be reintroduced once the
bone is healed. 
- In patients whose treatment with oral biphos-
phonates lasts longer than 3 years, independently
of having taken oral corticoids or not, the taking
of biphosphonates should be stopped at least 3
months before surgery if the systemic conditions
of the patient permit. The administration of
biphosphonates would be restarted only when the
bone had healed. 
Similarly, the Spanish Society for Bone and
Mineral Metabolism Research (SEIOMM) and the
societies related to bone mineral metabolism  have
produced a document on the management of ONJ
and the biphosphonates used in the treatment of
osteoporosis2:
- In patients taking biphosphonates for less
than 3 years and without risk factors it is not
necessary to delay surgery
- In patients taking biphosphonates for less
than 3 years and associated corticotherapy the
biphosphonates should be discontinued three
months before surgery, except where there is a
high risk of fracture (age > 70 years, presence of
earlier fracture, bone densitometry with a T-score
of <-2.0). It would be reintroduced once the hea-
ling had occurred.
- With patients who are taking biphosphonates
for more than 3 years the biphosphonates should
be discontinued 3 months before surgery, except
if there is a high risk of fracture (age > 70 years,
presence of previous fracture, bone densitometry
with a T-score <-3.0). It would be reintroduced
once healing had taken place.
Therefore, and in conclusion, ONJ is a little-
understood but increasingly frequent pathology
related to the taking of oral biphosphonates. New
protocols and consensuses around the activity in
relation to  a patient taking oral biphosphonates
over the long term and who is going to have oral
surgery, will in future be the determining factor in
avoiding, as much as possible, the development of
ONJ.
None of the authors has a conflict of interest.
Figure 2. Control orthopantomography in which is
seen the satisfactory development of bone re-ossifica-
tion of the osteonecrosis in the mandible
Figure 1. Orthopantomography and TAC which
shows osteonecrosis in the right mandibular body
CLINICAL NOTE / Rev Osteoporos Metab Miner 2012 4;1:37-41
40
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Table 1. Data from patients taking oral biphosphonates who develop ONJ (iv: intravenous therapy)
Table 2. Stages of ONJ according to the American Society of Oral and Maxillofacial Surgery9
Sex Age History ofinterest
Bisphosphonate
oral
Cause
of
treatment
Duration
of
treatment
Stadium
ONJ Treatment
Case 1 F 70 Bronchial asthma,dental extraction
Ibandronic acid
(150 mg monthly)
Postmenopausal
osteoporosis 4 years III
Bone curettage
+
iv antibiotherapy
Case 2 F 75
Recurrent
polychondritis,
dental extraction
Alendronate
(70 mg weekly)
Senile
osteoporosis 4 years II iv antibiotherapy
Case 3 F 81 Bronchial asthma,dental manipulation
Alendronate
(70 mg sweekly)
Senile
osteoporosis 3 years III
Bone curettage
and exodontia +
iv antibiotherapy
Case 4 F 76 Rheumatoid arthritis,dental extraction
Alendronate
(70 mg weekly)
Senile
osteoporosis 5 years III
Bone curettage 
+
iv antibiotherapy
Case 5 F 74 Dentalmanipulation
Alendronate
(70 mg weekly)
Senile
osteoporosis 4 years III
Bone curettage
+
iv antibiotherapy
Exposure of
necrotic bone
Pain and signs
of infection
Fistula and clinical or
radiographical evidence of
sequestered bone 
Degree I Yes No No
Degree II Yes Yes No
Degree III Yes Yes Yes
CLINICAL NOTE / Rev Osteoporos Metab Miner 2012 4;1:37-41
41
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necrosis of the jaw caused by soft tissue toxicity? Bone
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PS, Margonar R, Rastelli AN, et al. Accurate approach
in the treatment of oral bisphosphonate-related jaw
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Osteonecrosis of the jaw associated with the use of oral biphosphonates: apropos five cases

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Osteonecrosis of the jaw associated with the use of oral biphosphonates: apropos five cases

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