Bisphosphonate-related

osteonecrosis of the maxilla

and
sinusitis maxillaris
Int. J. Oral Maxillofac. Surg. 2011; 40: 285291. # 2010 International
Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights
reserved.

Objectives

Frequency of coincidental maxillary BRONJ, with

special attention to coincidental sinusitis
maxillaries
Evaluate outcome therapy

Key words :
Bisphosphonate, bisphosphonate related
osteonecrosis of the jaw, sinusitis maxillaris,
cancer treatment,osteoporosis

Bisphosphonates (BPs)

Two phosphonate (PO3)

groups
Use in bone mass loss
therapy:
- preventing bone mass loss,
- encouraging osteoclasts to
undergo apoptosis

Bisphosphonates (BPs)
Side effect

Treatment

acute renal
failure
gastrointestinal
disorders

hypocalcaemi
a

BPs
(bone stabilizer
ability to
inhibit
osteoclast

osseous
metastases
osteoporosis

Pagets disease
bisphosphonaterelated
osteonecrosis of
the jaw (BRONJ)

BRONJ

exposed, nonvascularized,
and necrotic bone tissue in
the oral cavity
Frequently combined with
inflammation of the
surrounding tissue and pain
Estimated incidance 8 12 %
( more frequently in mandible
than maxillary)
Resistant to antibiotics
management remains difficult
and includes surgical
procedure to eradicate the
necrotic bone

BRONJ

The diagnosis of BRONJ relies on 3 criteria:

Must be taking or have taken bisphosphonate
medication
exposed bone in the jaw persisting for more
than 8 weeks
no history of radiation theraphy to the head
and neck

Image of the exposed necrotic

bone in the maxillary area

DVT scan with BRONJ-related brightening of the right

maxillary area and shading of the ipsilateral sinus
maxillaris.

BRONJ STAGING

based on the classification established by RUGGIERO et al.

and the American Association of Oral and
Maxillofacial Surgeons (AAOMS)

Stage 0

Stage 1

no clinical
evidence of necrotic bone, but
presenting
with non-specific symptoms or clinical
and radiographic findings.

exposed/necrotic bone in patients

who area symptomatic and have no
evidence of infection or patients
symptomatic with pain prior to
clinical evidence of exposed bone or
radiographic changes

BRONJ STAGING

based on the classification established by RUGGIERO et al.

and the American Association of Oral and
Maxillofacial Surgeons (AAOMS)

Stage II

exposed/necrotic bone associated with an

infection as evidenced
by pain and erythema in the region
of the exposed bone with or without
purulent drainage

Stage III

exposed/necrotic bone associated

with pain, infection, and one or more of
the following: a pathologic fracture, an
extraoral fistula, or osteolysis extending
into the inferior border or sinus floor

10

sinusitis maxillaris

Sinusitis is characterized by quantitative and

qualitative changes in mucus biosynthesis
that contribute to sinus disease

11

sinusitis maxillaris
Classified etiologically :
1. Rhinogenic
2. Odontogenic

12

Materials and methods

All patients presenting with BRONJ of the maxilla
between January 2005 and July2008 were evaluated in
terms of frequency and therapeutic outcome, with
special attention paid to patients with an associated
sinusitis maxillaris

All patients were examined clinically

(including dental status and tooth sensibility)
and radiologically with digital
volume tomography

Using a standardized questionnaire, data

were collected on BP therapy, its duration,
and the manner of application
13

Manajement and outcome

Management was based on the results of

BRONJ staging

All patients received antibiotics (2 g of

amoxicillin plus 200 mg of clavulanic
acid intravenously (i.v.) every 8 h) in
combination with an intraoral
chlorhexidine rinse at least 14days prior
to any intervention

14

Manajement and outcome

Stage 0 or I cases, surgical intervention was
restricted to debridement of soft tissue
Stage II or III cases, a segmental bone
resection under general anaesthesia was
performed
Patients with sinusitis were treated with
antibiotics

If the sinusitis persisted after five days of antibiotic treatment

an antrotomy was performed. Afollow-up included clinical and
radiological
examinations every six months with special attention paid to the
recurrence ofBRONJ and sinusitis maxillaris
15

Result
remarks :

A : 98 patients were
diagnosed with BRONJ
between January 2005
and July 2008

B : 21 suffered from
maxillary BRONJ
average age : 69 ( 48
91 years)

A
B

16

Result

Bisphosphonate manner :
- iv for malignancies therapy : 18 (86%)
- po for osteoporosis therapy : 3 (14%)
Got chemotherapy
- underwent chemotherapy : 16 (76%)
Risk Factors :
- hypertension : 7 (3%)
- vascular disease : 5 (24%)
- diabetic mellitus : 2 (10%)
Presenting of BRONJ
- spontaneously developed BRONJ : 12 (57%)
- underwent dentoalveolar procedure : 9 (43%)

17

Result

Kind of drug
- zoledronate i.v : 15 (71%)
- ibandronate i.v : 3 (4%)
- alendronate p.o: 3 (4%)
Duration time of presenting BRONJ : average : 47.4
months
Exposure time :average : 48.4 months
- zoledronate i.v : 47.4 (71%)
- ibandronate i.v : 20 (4%)
- alendronate p.o: 60,7 (4%)

18

Result

Presenting of mucosal dehiscence and exposure of

necrotic bone
- molar region : 16 (76 %)
- incisor region : 4 (14% )
- no dehiscence : 1 (5%)
Staging of BRONJ
- stage 0 : 1
- stage 1 : - stage 2 : 10 (48%)
- stage 3 : 10 (48%)

19

Result

The staging of the BRONJ

- ibandronate < zolendronate
- ibandronate = alendronate
The BRONJ suffered from an ipsilateral sinusitis
maxillaris
- 10 patients (48%, female, average age 69,7%, stage
III)
Therapy
- 19 cases (stage II & III), bone resection under GA
Relaps of BRONJ
- 6 cases (29%, 2 patients stage II , 4 patients stage
III related relaps of sinusitis maxillaris)
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Discussion
BP Administration

Apoptosis

osteocyt

angio
genesis
-Blood
vessel
obstruction

osteosclerosis

Proliferation
Adherence
to jawbones
(biofilm)

Priloferatio
n, migration
of oral
epetelial
cells

Aging
Anticancer
therapy

Bone resobtion
Remodelling

Surgical
trauma

Removal necrotic
bone

Closure
socket

Immune
function

Oral bacterial
infection

Wound healing

BRONJ
21

Conclusion
Percentage of patients presenting with
severe maxillary BRONJ suffer from an
associated sinusitis maxillaris that is
frequently resistant to therapy, similar to
BRONJ itself
Regular monitoring of patients by dentists
and maxillofacial surgeons throughout BP
therapy is essential and should include
paranasal sinus diagnostics
22

Thank you

23

Bone Turnover Markers

A summary list of bone formation markers is as follows:

Serum
Serum
Serum
Serum

total alkaline phosphatase

bonespecific alkaline phosphatase
osteocalcin
type 1 procollagen (C-terminal/N-terminal): C1NP or P1NP

A summary list of bone resorption markers is as follows:

Urinary hydroxyproline
Urinary total pyridinoline (PYD)
Urinary free deoxypyridinoline (DPD)
Urinary collagen type 1 cross-linked N-telopeptide (NTX)
Urinary or serum collagen type 1 cross-linked C-telopeptide (CTX)
Bone sialoprotein (BSP)
Tartrate-resistant acid phosphatase 5b

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What are the risk factors for Bis-phosphonateassociated ONJ?

Use of high-dose IV bis-phosphonate

Longer duration of treatment with bis-phosphonate

Steroid use (Prednisolone, Dexamethasone etc.)

Alcohol abuse and tobacco use

People suffering from cancer

Poor dental hygiene and those who undergo a dental

procedure such as dental extraction

Diabetes mellitus

25

What are the symptoms of BRONJ?

Severe jaw pain

Numbness of the jaw

Swelling and infection of the jaw region

Loosening of teeth and exposed bone

26

Preventive strategy to identify patients at risk of

developing bisphosphonate-associated osteonecrosis
of the jaw

27

Mechanism of bisphosphonate accumulation in the jaw

and a hypothetical pathogenic role in osteonecrosis

28

29

Fracture healing

Fracture results in a series of tissue responses

that remove tissue debris, re-establish the
vascular supply, and produce new skeletal
matrix (Simmons, 1985).
Unlike the healing processes of other tissues,
which produce scar tissue, bone has the ability
to repair itself.
Once a fracture has healed and undergone
remodeling, the structure will have returned to
the preinjurystate. There are two main types of
fracture healing: Primary and secondary.
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