Transcript Case reports of BRONJ 指導老師: 王文岑醫師暨口腔病理科全體醫師 實習E組 Intern 廖昱豪 張庭維

Case reports of BRONJ
指導老師: 王文岑醫師暨口腔病理科全體醫師
實習E組 Intern 廖昱豪
張庭維
謝旻芸
黃于芳
曾家展
Case 1
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General data
Name :葉x英
Gender: Female
Age : 76 y/o
Native : 屏東縣
Marriage status : Married
Occupation : 無
Chief Complaints
R’t submandibular swelling for 2 months
Present Illness
• 97.12.11
– This 74 y/o female was suffered from the
above episode, at first she went to LDC , the
dentist suggest ed her to come to our OPD
for further examination. She took Fosamax.
– 2 polyps at right edentulous ridge, local pus
(+)
– Right submandibular swelling about 5*7cm
Past History
Past Medical History
• Hypertension(+) DM(-) denied other systemic
illness
• Hospitalized:置換人工膝關節
• osteoporosis
• drug or food allergy: penicillin
• Medication:
drug for hypertension control
膝關節藥物
Forsamax (alendronate(口服) 次/週 for 4~5 yrs )
• Past Dental History
Extraction ,C&B,OD,RCT
• Attitude to Dental Tx：Fair
• Oral Habits
Alcohol : (-)
Betel quid : (-)
Cigarette (-)
• 3x3 cm
• Mixed RL with RO, irregular shape bony
destruction
Differential Diagnosis
●Infection
●Tumor
Osteomylities • Benign (X)
• Malignancy
osteosacoma
odontogenic malignancy tumor
Clinical impression
• Bisphosphonate- related osteonecrosis of
jaw (BRONJ)
Treatment course
• 97.12.11 (first visit) refer from LDC
I&D
anaerobic culture, aerobic culture
Rx: amoxicillin/ panadol / suwell
• 97.12.18
pus culture report
Clostridium bifermentans
→metronidazole(+) Ampicillin (+)
Clindamycin (+)
• 97.12.12~97.12.31
N/S irrigation
Antibiotic
• 98.1.7
arrange OP
• 98.1.15
OP: sequestrectomy +saucerization
• 98.3.4
• 98.5.6
Remove sequestrum (in OPD)
• 98.9.16
F/U
Case 2
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General data
Name : 涂沈秀月
Gender: Female
Age : 51 y/o
Native : Kaohsiung
Marriage status : Married
First Visit : 97/12/18
Chief Complaints
• Ask for oral examination for dental care
after 骨針 application
• Bad smell from wound of extraction for
more than 1 year.
Present Illness
• 97/12/18
This 49 y/o female has received Zometa
IV monthly for bone metastasis for about 3
years. And the nurse of cancer center
suggested her to visit our OPD for oral
examination.
She stated she had extraction
experience of teeth 15 and 16 more than
1 year ago in LDC.
Past History
Past Medical History
• Breast carcinoma with bone metastasis
(T1N2M1)s/p operation , systemical
chemotherapy and radiotherapy.
• Serous microcystic adenoma over pancreatic tail
s/p partial pancreatectomy
• Otitis media s/p eardrum reconstraction
• Tonsil excision
Past Dental History
• Extraction, C&B fabrication, OD, scaling
Attitude to Dental Tx：Fair
Oral Habits Related to Malignancy:
• Alcohol : (-)
• Betel quid : (-)
• Cigarette : (-)
Oral Examination
• A fistula was found on edentulous ridge of teeth
15 &16, tracing with GP to take a periapical film.
• Missing:
– 15,16,17,18,27,28,37,38,45,46,48
• Caries : 13(D),14(M),34(B)
• Metal crown : 22,23,24,25,26,35,36,44xx47
• PFM crown: 42
Panorex findings
There is an ill-defined bony destruction area
about 2x2cm in diameter over edentulous ridge
of teeth 15 and 16 .
Differential diagnosis
• Bisphosphonate related osteomyelitis over R’t
post. Maxilla
• Breast carcinoma with bone metastasis of jaw
• Osteoradionecrosis of the jaw (ORN)
Clinical Impression :
Bisphosphonate-Related Osteonecrosis of the
Jaw (BRONJ)
Treatment Plan
• Antibiotic therapy
• Local debridement
• Advanced surgical management
98.8.13
Cases review of BRONJ
(KMUH)
Cases review
•Patient source:
14 BRONJ patients in KMUH dental dept.
•Methods: chart review
1.bisphosponate(BP) usage
2.radiographic evaluation
3.systemic condition
4.oral hygiene and dental
condition
General data
Sex:
Male : Female = 0:14 (female 100%)
Age:
21-50 y/o: 1 (7.1%)
51-60 y/o: 2 (14.2%)
61-70 y/o: 3 (21.3%)
71-80 y/o: 6 (42.6%)
81-90 y/o: 2 (14.2%)
Range: 42-82, average : 69 y/o
Reason for BP usage:
Breast ca (BC) with bone meta or prevention: 6(42.8%),
Osteoporosis: 8(57.2%)
DM: 5 (35.5 %)
Used form of BP
• BC
Oral
IV
Oral+IV
• O
A :8 (oral)
P: pamidronate
Z
P+Z
3
2
B+Z
1
Using time of BP(months)
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11-30m: 3
31-50m: 6
51-70m: 1
71-90m: 2
101-110m: 1
• Side effect:
not obvious
• Minimum: 13m (A/oral)
• Maximum:103m
(A/oral)
• Average: 47m
Lesion characteristics
• Bony exposure:12/14(85.7%)
• Lesion Numbers
0
1
1(7.1%)

8(57.1%)
2
3
4(28.6%)
1(7.1%)
Locations
Location
Upper
Ant.
Upper
premolar
Upper
molar
Lower
anterior
Lower
premolar
Lower
molar
No.(%)
1 (5.6%)
2 (11.1%)
2(11.1%)
2(11.1%)
4(22.2%)
7(38.9%)
Clinical characteristics
•Symptoms and signs
Pain
14/14
100%
Swelling
9/14
64.3%
Delayed healing wound (sockets)
11/14
78.6%
neurosensory changes
3/14
21.4%
Pus
13/14
92.9%
Intraoral sinus tract
extraoral fistula
8/14
57.1%
Tooth mobility
5/14
35.7%
X ray finding
14/14
100%
1
3
2
1
Clinical characteristics
• Radiographic features
Radiolucency
RO
mixed
10 (71.4%)
0
4 (28.6 %)
• Lesion size
Maxium: 5*3 cm
Minimum: 1*1 cm
•ONJ staging
0
0
1
1/14
(7.1%)
2
12/14
(85.7%)
3
2/14
(14.3%)
• Special events
none
2/14
(14.3%)
extraction
Other
11/14 (78.6%) 1/14
(tooth Fx)
(7.1%)

Event~ BRONJ
< 1m
2
1m
4
2~3m
1
12m
1
• 使用bisphosphonate 到發病時間
11~30m
31~50m
51~70m
71~90m
91~110m
4
4
2
1
1
Minima: 12 Maxima: 94 Average: 44.8
Clincal procedures & treatments
• Biopsy: 7/14 (50%)
• Bacterial culture: 6/14 (42.9%)
Clostridium bifermentans
staphylococus epidermidis
propionibacterium species
• Antibiotic: 14/14 (100%)
amoxicillin, clindamycin, metronidazole, clindamycin,
• Local irrigation and debridement: 12/14 (85.7%)
• Operation (in OR) : 6/14 (42.9%)
• HBO : 4/14 (28.6%)
• Periodontitis: 12/14
(85.7%)
• 感染性骨髓炎:
Upper
anterior
Upper
premolar
Upper
molar
Lower
anterior
Lower
premolar
Lower
molar
3 site
0 site
0 site
3 site
7 site
8 site
conclusion
• 更年期過後的婦女因為罹患乳癌和骨質疏鬆症的
機率增加，用藥機率增加，所以為高危險群
• 藥物本身副作用不明顯，所以使用普遍
• 11/14 (78.6%)的病人是因為拔牙傷口不癒合，且
大多數病灶部位都在下顎後牙區
• 病患大多在服藥後1~5年內發病，平均44.8m
• 所有來診的患者皆有疼痛(100%)的情況，其次為
化膿(92.9%) ，可見一般民眾會因為疼痛尋求解
決，或是化膿意識到嚴重性求診
Discussion
INDICATIONS AND BENEFITS OF
BISPHOSPHONATE
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Bps. have high affinity for hydroxyapatite , remaining
unmetabolized for long periods of time.
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During bone remodeling, the drug is taken up by
osteoblast and internalized in the cell cytoplasm.
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Reducing recruitment and proliferation of osteoclast
precursors and inducing osteoclast apoptosis.
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As a result, bone turnover becomes
profoundly suppressed, and over time the
Bps. also have antiangiogenic properties and may be
bone shows
little physiologic remodeling.
directly
tumoricidal.
INDICATIONS AND BENEFITS OF
BISPHOSPHONATE THERAPY
• IV Bisphosphonates
cancer-related conditions
1.hypercalcemia of malignancy
2.bone metastases (breast cancer, prostate cancer ,
lung cancer)
3.lytic lesions of multiple myeloma
• Pamidronate(Aredia), Zoledronic acid(Zometa),
Zoledronate(Reclast), Ibandronate(Boniva)
J Oral Maxillofac Surg 67:2-12, 2009, Suppl
• Oral Bisphosphonates
1. most prevalent and common indication  osteoporosis
2. Paget’s disease of bone and osteogenesis imperfecta of
childhood.
• Off-label uses
 Numerous other conditions where a decrease in bone
remodeling by bisphosphonates might aid in disease
management:
– giant cell lesions of the jaw
– pediatric osteogenesis imperfecta
– fibrous dysplasia
– Gaucher’s disease
J Oral Maxillofac Surg 67:2-12, 2009, Suppl
Common bisphosphonates
Relative Potency
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Etidronate (Didronel)
Tiludronate (Skelide)
Pamidronate (Aredia)
Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)
Zolendronic acid (Zometa)
*Relative
1
10
100
1,000
10,000
10,000
>100,000
to etidronate (a non-nitrogen-containing
bisphosphonate with relative potency of 1).
BRONJ Case Definition
Patients may be considered to have
BRONJ
1. Current or previous treatment
with a bisphosphonate.
2. Exposed bone in the maxillofacial
region that has persisted for
more than 8 weeks.
3. No history of radiation therapy to
the jaws
J Oral Maxillofac Surg 67:2-12, 2009, Suppl
Incidence of BRONJ
Independent
epidemiological efforts from clinicians and
• IV BISPHOSPHONATES
the International Myeloma Foundation reported
• 0.8% estimates
to 12% between 5% ~ 10%.
incidence
• ORAL BISPHOSPHONATES
 0.7/100,000 person-years of
exposure(Merck)underreporting.
 Surveillance data from Australia (patients treated weekly with
alendronate )  0.01% to 0.04%
 13,000 Kaiser-Permanente members( long-term oral bps)
0.06%
 IV>>oral.
J Oral Maxillofac Surg 67:2-12, 2009, Suppl
RISK FACTORS
1. Drug-related risk factors
A. Bisphosphonate potency
zoledronate (Zometa)> pamidronate(Aredia)> oral bps.
B. Duration of therapy
2. Local risk factors
A. Dentoalveolar surgery: 5-~21-fold increased risk in IV Bps.
treated cancer patients.
B. Local anatomy : Mandible : Maxilla=2:1
(Thin mucosa overlying bony prominences such as tori , bony
exostoses, and the mylohyoid ridge)
C. Concomitant oral disease: history of inflammatory dental
disease are at a 7-fold increased risk.
J Oral Maxillofac Surg 67:2-12, 2009, Suppl
3. Demographic and systemic factors
A. increasing age ; whites.
B. systemic factor (renal dialysis, low hemoglobin, obesity,
and diabetes)
C. chemotherapeutic agents (cyclophosphamide,
erythropoietin, and steroids)
D. tobacco users, alcohol exposure(X)
…Wessel et al
4. Genetic factors
single nucleotide polymorphisms, in the cytochrome
P450-2C gene [CYP2C8]
……… Sarasquete et al
J Oral Maxillofac Surg 67:2-12, 2009, Suppl
Staging of BRONJ
• Patient at risk :
no apparent necrotic bone in asymptomatic patients who
have been treated with IV or oral Bps.
• Stage 0 : no clinical evidence of necrotic bone, present with
nonspecific symptoms or findings, include
Clinical
findings:
Symptoms:
1. Loosening
teeth
not explained
1. Odontalgia
not byofan
odontogenic
cause
2. Fistula not associated with pulpal necrosis
2. Dull, aching
bone pain in the body of the mandible
Radiographic
findings:
3. Sinus
pain
1. Persistence
of unremodeled bone in sockets
2. Thickening/obscuring
of periodontal ligament
4. Altered
neurosensory function
3. Inferior alveolar canal narrowing
• Stage1 : exposed and necrotic bone in patients
who are asymptomatic and have no evidence of
infection.
• Stage2 : exposed and necrotic bone in patients
with pain and clinical evidence of infection(pain,
erythema , purulent drainage.)
• Stage3: exposed and necrotic bone in patients with
pain, infection, and one or more of the following:
1. Exposed necrotic bone extending beyond the region of
alveolar bone
2. Pathologic fracture
3. Extraoral fistula
4. Oral antral/oral nasal communication
5. Osteolysis extending to the inferior border of the
mandible or sinus floor
Treatment stretagy
At risk: Not require any treatment.
Patient education.
Stage 0:
Systemic management, including
use of pain medication and antibiotics
Stage 1:
Antibacterial mouth rinse(0.12% CHX)
Clinical follow-up
No surgical treatment is indicated.
Stage2:
• Symptomatic treatment with oral antibiotics
(adjusted according to culture )
• Oral antibacterial mouth rinse
• Pain control
• Superficial debridement to relieve soft tissue
irritation.
Stage3:
• Antibacterial mouth rinse
• Antibiotic therapy and pain control
• Surgical debridement / resection for longer term
palliation of infection and pain.
Treatment strategy and advisements
Patients About to Initiate IV:
• If systemic conditions permit, initiation of Bps. therapy
should be delayed until the dental health has been
optimized.
• if systemic conditions permit, until the extraction site has
mucosalized (14 to 21days) or until adequate osseous
healing has occurred.
• Patients be educated as to the importance of dental
hygiene and regular dental evaluations and specifically
instructed to report any pain, swelling , or exposed.
Asymptomatic Patients Receiving IV Bisphosphonates:
• Avoid direct osseous injury .
• The efficacy of a drug holiday for patients receiving yearly
zoledronic acid therapy and the appropriate timing of
dentoalveolar surgery is unknown.
Asymptomatic Patients Receiving Oral
Bisphosphonate :
• A. Patients are adequately informed of the small risk of
compromised bone healing.
• B. The use of bone turnover marker levels, in conjunction
with a drug holiday, has been reported as an additional
tool to guide treatment decision.
C. For individuals taken an oral bps. for fewer than 3 years and
have no clinical risk factors.
no alteration or delay in the planned surgery is necessary.
D. For fewer than 3 years and have also taken corticosteroids
concomitantly
 consider discontinuation of the oral bps. for at least 3
months before & after oral surgery.
Patients with BRONJ
• Treatment objectives eliminate pain, control infection of
the soft and hard tissue, and minimize the progression or
occurrence of bone necrosis.
• Surgical debridement is variably effective
Difficult to obtain a surgical margin in early stage.
 Surgical treatment should be delayed if possible.
• Stage 3 disease might require resection and immediate
reconstruction with a reconstruction plate or an obturator .
• Hyperbaric oxygen therapy has some
improvement in wound healing and long-term
pain scores, but its use as the sole treatment
modality for BRONJ cannot be supported at this
J Oral Maxillofac Surg 67:96-106, 2009, Suppl 1
time.
• Other non-invasive treatment:
platelet-rich plasma, parathyroid hormone, and
bone morphogenic protein..-->need more study.
J Oral Maxillofac Surg 2007; 65: 573- 80.
• Mobile segments of bony sequestrum should be
removed .
• Extraction of symptomatic teeth within exposed,
necrotic bone should be considered because it is unlikely
that extraction will exacerbate established necrotic
process.
• Long-term discontinuation of IV Bps might be beneficial.
(1~2 years)
• Discontinuation of oral Bps for 6-12 months may result in
either spontaneous sequestration or resolution after
debridement surgery.
Thank you for your attention!!