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
Download
Report
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
•
•
•
•
•
•
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
•
•
•
•
•
•
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)
•
•
•
•
•
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
•
Bps. have high affinity for hydroxyapatite , remaining
unmetabolized for long periods of time.
•
During bone remodeling, the drug is taken up by
osteoblast and internalized in the cell cytoplasm.
•
Reducing recruitment and proliferation of osteoclast
precursors and inducing osteoclast apoptosis.
•
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
•
•
•
•
•
•
•
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!!