Case reports of BRONJ

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Case reports of BRONJ

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General data
Case 1

• Name ?x?
• Gender Female
• Age 76 y/o
• Native ???
• Marriage status Married
• Occupation ?

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Chief Complaints

• Rt submandibular swelling for 2 months

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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 57cm

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Past History

• Past Medical History
• Hypertension() DM(-) denied other systemic
  illness
• Hospitalized???????
• osteoporosis
• drug or food allergy penicillin
• Medication
• drug for hypertension control
• ?????
• Forsamax (alendronate(??) ?/? for 45 yrs )

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• Past Dental History
• Extraction ,CB,OD,RCT
• Attitude to Dental TxFair
• Oral Habits
• Alcohol (-)
• Betel quid (-)
• Cigarette (-)

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• 3x3 cm
• Mixed RL with RO, irregular shape bony
• destruction

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Differential Diagnosis
?Infection Osteomylities

• ?Tumor
• Benign (X)
• Malignancy
• osteosacoma
• odontogenic malignancy tumor

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Clinical impression

• Bisphosphonate- related osteonecrosis of jaw
  (BRONJ)

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Treatment course

• 97.12.11 (first visit) refer from LDC
• ID
• anaerobic culture, aerobic culture
• Rx amoxicillin/ panadol / suwell
• 97.12.18
• pus culture report
• Clostridium bifermentans
• ?metronidazole() Ampicillin ()
• Clindamycin ()

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• 97.12.1297.12.31
• N/S irrigation
• Antibiotic
• 98.1.7
• arrange OP
• 98.1.15
• OP sequestrectomy saucerization

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• 98.3.4

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• 98.5.6
• Remove sequestrum (in OPD)

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• 98.9.16 F/U

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General data
Case 2

• Name ????
• Gender Female
• Age 51 y/o
• Native Kaohsiung
• Marriage status Married
• First Visit 97/12/18

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Chief Complaints

• Ask for oral examination for dental care after ??
  application
• Bad smell from wound of extraction for more
  than 1 year.

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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.
  

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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

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• Past Dental History
• Extraction, CB fabrication, OD, scaling
• Attitude to Dental TxFair
• Oral Habits Related to Malignancy
• Alcohol (-)
• Betel quid (-)
• Cigarette (-)

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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

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Panorex findings
There is an ill-defined bony destruction area
about 2x2cm in diameter over edentulous ridge of
teeth 15 and 16 .
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Differential diagnosis

• Bisphosphonate related osteomyelitis over Rt
  post. Maxilla
• Breast carcinoma with bone metastasis of jaw
• Osteoradionecrosis of the jaw (ORN)

Clinical Impression Bisphosphonate-Related
Osteonecrosis of the Jaw (BRONJ)
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Treatment Plan

• Antibiotic therapy
• Local debridement
• Advanced surgical management

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98.8.13
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• Cases review of BRONJ (KMUH)

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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

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General data

• Sex
• Male Female 014 (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 )

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Used form of BP

• BC

Z PZ BZ
Oral
IV 3 2
OralIV 1

• O
• A 8 (oral)
• P pamidronate

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Using time of BP(months)

• 11-30m 3
• 31-50m 6
• 51-70m 1
• 71-90m 2
• 101-110m 1
• Minimum 13m (A/oral)
• Maximum103m (A/oral)
• Average 47m

• Side effect
• not obvious

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Lesion characteristics

• Bony exposure12/14(85.7)
• Lesion Numbers

0 1 2 3
1(7.1) 8(57.1) 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)
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Symptoms and signs
Clinical characteristics
Pain 14/14 100 1
Swelling 9/14 64.3
Delayed healing wound (sockets) 11/14 78.6 3
neurosensory changes 3/14 21.4
Pus 13/14 92.9 2
Intraoral sinus tract extraoral fistula 8/14 57.1
Tooth mobility 5/14 35.7
X ray finding 14/14 100 1
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Clinical characteristics

• Radiographic features

Radiolucency RO mixed
10 (71.4) 0 4 (28.6 )

• Lesion size
• Maxium 53 cm
• Minimum 11 cm

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ONJ staging
0 1 2 3
0 1/14 (7.1) 12/14 (85.7) 2/14 (14.3)

• Special events

none extraction Other
2/14 (14.3) 11/14 (78.6) 1/14 (tooth Fx) (7.1)
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• Event BRONJ

lt 1m 1m 23m 12m
2 4 1 1

• ??bisphosphonate ?????

1130m 3150m 5170m 7190m 91110m
4 4 2 1 1
Minima 12 Maxima 94 Average 44.8
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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)

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• Periodontitis 12/14 (85.7)
• ??????

Upper anterior Upper premolar Upper molar Lower anterior Lower premolar Lower molar
3 site 0 site 0 site 3 site 7 site 8 site
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conclusion

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• ??????????,??????
• 11/14 (78.6)?????????????,???????????????
• ????????15????,??44.8m
• ???????????(100)???,?????(92.9)
  ,???????????????,????????????

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Discussion
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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.
• Bps. also have antiangiogenic properties and may
  be directly tumoricidal.

As a result, bone turnover becomes profoundly
suppressed, and over time the bone shows little
physiologic remodeling.
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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 672-12, 2009, Suppl
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• Oral Bisphosphonates
• most prevalent and common indication ?
  osteoporosis
• Pagets 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
• Gauchers disease

J Oral Maxillofac Surg 672-12, 2009, Suppl
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Common bisphosphonates
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Relative Potency

• Etidronate (Didronel) 1
• Tiludronate (Skelide) 10
• Pamidronate (Aredia) 100
• Alendronate (Fosamax) 1,000
• Risedronate (Actonel) 10,000
• Ibandronate (Boniva) 10,000
• Zolendronic acid (Zometa) gt100,000

Relative to etidronate (a non-nitrogen-containing
bisphosphonate with relative potency of 1).
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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 672-12, 2009, Suppl
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Incidence of BRONJ
Independent epidemiological efforts from
clinicians and the International Myeloma
Foundation reported incidence estimates between
5 10.

• IV BISPHOSPHONATES
• ?0.8 to 12
• ORAL BISPHOSPHONATES
• 0.7/100,000 person-years of exposure(Merck)?underr
  eporting.
• 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
• IVgtgtoral.

J Oral Maxillofac Surg 672-12, 2009, Suppl
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RISK FACTORS

• 1. Drug-related risk factors
• A. Bisphosphonate potency
• zoledronate (Zometa)gt
  pamidronate(Aredia)gt 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 Maxilla21
• (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 672-12, 2009, Suppl
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• 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 672-12, 2009, Suppl
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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
• Symptoms
• 1. Odontalgia not by an odontogenic cause
• 2. Dull, aching bone pain in the body of
  the mandible
• 3. Sinus pain
• 4. Altered neurosensory function

Clinical findings 1. Loosening
of teeth not explained 2. Fistula
not associated with pulpal necrosis Radiographic
findings 1. Persistence of
unremodeled bone in sockets
2. Thickening/obscuring of periodontal
ligament 3. Inferior alveolar
canal narrowing
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• Stage1 exposed and necrotic bone in patients
  who are asymptomatic and have no evidence of
  infection.

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• Stage2 exposed and necrotic bone in patients
  with pain and clinical evidence of
  infection(pain, erythema , purulent drainage.)

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• Stage3 exposed and necrotic bone in patients
  with pain, infection, and one or more of the
  following
• 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

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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.

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• 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.
•  

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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.

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• 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.

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• 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.

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• 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 .

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• 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 time.
• Other non-invasive treatment
• platelet-rich plasma, parathyroid hormone,
  and bone morphogenic protein..--gtneed more study.

J Oral Maxillofac Surg 6796-106, 2009, Suppl 1
J Oral Maxillofac Surg 2007 65 573- 80.
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• 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.
• (12 years)
• Discontinuation of oral Bps for 6-12 months may
  result in either spontaneous sequestration or
  resolution after debridement surgery.

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Thank you for your attention!!