MRONJ

Question 1

Is MRONJ Avascular? Is osteomyelitis involved?

Answer 1

Dr. F says that vasculature is still present and should not be called avascular necrosis.

Yes osteomyelitis usually detected

Question 2

What is MRONJ?

Answer 2

Medication related osteonecrosis of the jaw

Patient had history of antiresorptives or antiangiogenics

No history of radiation of mets to jaw

Exposed bone of fistula >8 weeks

Question 3

What are other clnical and radiographic signs of MRONJ?

Answer 3

Pain/paresthesia

Osteosclerosis

PDL widening

Question 4

What scan is useful in identifying MRONJ “hotspots”?

Answer 4

PET CT - used to guide diagnosis and surgery

1 mm cuts of mandible and maxilla

Question 5

what are 3 theoretical etiologies of MRONG?

Answer 5

1. infection/biofilm
2. altered bone remodeling
3. altered host immune system

Question 6

Altered bone remodeling/ Over Suppression Hypothesis? What is it?

What doesn’t work with this theory?

Answer 6

The hypothesis contends that jaw bones undergoes a higher remodeling/bone turnover rate compared to other bones. So antireportives are preferential to the jaws = increased MRONJ risk.

This theory doesn’t work because bone turnover in the jaws was found to be no different than bone turnover elsewhere in the body

Question 7

What are biofilms? How are they involved in MRONJ?

Answer 7

they produce and polymeric polysaccharide “shield” making them resistant to host defenses. The cell colonies have increased antibiotic resistance. Also host has altered immune response leading to increased pathologic bacteria.

Question 8

Are bisphosphonates worth it?

Answer 8

YES!!!

They maintain normal bone health in osteoporosis (preventing fractures and pain) and in metastatic bone cancers.

they also treat hypercalcemia possibly improving survival in patients.

Benefits»> Risks

Question 9

Can MRONJ occur without antiresorptives?

Answer 9

yes as ONJ but usually on other chemotherapeutics that affect immune response

VEGF inhibitors, steroids,

Question 10

Does poor oral health (perio and caries) correlate with MRONJ?

Answer 10

No, oral health is not correlated.

there is some association with periodontal disease

Question 11

How long after starting chemo therapy does MRONJ occur?

Answer 11

IV group within 1-2 years… not as clear with oral antiresorptives

Question 12

Triggers for MRONJ?

Answer 12

Extraction and spontaneous (infected tooth without surgery) are about equal risk

Question 13

What is denosumab?

Answer 13

Monoclonal antibody against RANKL (activates osteoclast) - may suppress immune response

Subcutaneous administration

Half life = 1 month - not retained in bone

Prolia = Osteoporosis
Xgeva = Metastasis

Question 14

Does fleischer use “drug holiday”? Avoiding extractions?

Answer 14

No and No - no data to support. He is film believer that infection causes MRONJ - requires removal of source and debridement as needed.

Question 15

Is CTX a useful correlate/diagnostic lab for risk of MRONJ?

What is CTX?

Answer 15

No it is not associated.

CTX is a normal byproduct of collagen after osteoclast metabolizes it. So the idea was increased BP = decreased osteoclasts and the effect can be measure via CTX an osteoclast byproduct. But it is unfounded and not to be used with the current science.

Question 16

Is biopsy recommended?

Is hematopathology testing (flow cytometry) recommended?

Answer 16

Yes - 5% incidence of metastatic disease.

Sometimes!

• flow cytometry analyzes quantity and characterics of cells and can find malignant plasma cells indicative of multiple myeloma.
• Immunohistochemistry can detect abnormal proteins like lambda protein excess secreted by multiple myeloma plasma cells.

Cytologists requires viable bone that surrounds the necrotic bone in particulate fashion - not block. Submit if fresh saline and send to lab asap.

Question 17

what is treatment for MRONJ?

What are the 5 goals of treatment?

Answer 17

Start conservatively - rinse and antibiotics with toothbrush daily debridement.

If no improvement or worsening symptoms consider debridement

1. Remove infection nidus.
2. Remove necrotic bone.
3. Remove of manage hypovascular bone.
4. Promote healing
5. Improve function

Question 18

What are the 4 stages of MRONJ?

Answer 18

Stage 0 = asymptomatic pain/symptoms - no bone

Stage 1= exposed bone > 8 weeks - asymptomatic

Stage 2 = Bone exposure and pain

Stage 3 = necrotic bone with pathologic fx or fistula (extraoral)

Question 19

Can cone beam be sued in the management of MRONJ?

Answer 19

Can be used to evaluate PDL widening, sequestration and sclerosis

Question 20

How are MMPs involved? (matrix metalloproteinase)

Answer 20

Chronic infection and inflammation (TMJ!) can increase MMP production which break down wounds and prevent healing.

Question 21

How is Doxycycline used to MRONJ?

Answer 21

Doxy is deposited in bone and reduces inflammatory destruction by reducing MMPs, collagenase and super oxide radicals.

It can aid in the MRONJ to delineate itself facilitating debridement/resection as the antibiotic won’t go to the dead or dying/hypovascular bone (dependent on osteoblasts and vasculature)

Question 22

Osteosclerosis a complication of MRONJ?

Answer 22

More likely a reaction to infection - body reacts by increasing density and decreasing vascularity of bone.

Decreasing vascularity allows bacteria to seed in bone = increased risk of infection long term.

Makes identifying healthy bone very difficult in surgery.

LONG TERM FOLLOW UP NEEDED IN PATIENTS WITH SCLEROSIS

Question 23

Is HBO a useful adjunctive treatment to MRONJ?

Answer 23

YES! HBO - stimulates angiogenesis and oxygenates sclerotic areas

• good for severe cases, sclerosis, 1 cm of inferior border is unaffected, smokers.
• 5-10 dives preop; 20-25 dives postop= likes more postop so it can stimulate healthy tissue.
• contraindicated on patients with near pathologic fx, patients unable to tolerate HBO, or end of life pts
• contraindicated on patients on Doxil, Cis-platinum, and bleomycin - must cessate drugs prior
• get through insurance by submitting biopsy to rule out osteomyelitis - if they can’t rule it out then insurance will pay for dives

Question 24

Does HBO affect cancers?

Answer 24

HBO has no impact on tumor growth as per current evidence

Question 25

Avelox? What is it? When is it used?

Answer 25

Oral abx for acute exacerbations and symptomatic infections - not primary therapy

4th generation fluoroquinolone

very broad spectrum and good against odontogenic pathogens

good bone penetration

Rx- 400mg qd

Risks = elevates INR - check with cardiologist a few days after

Question 26

What is Ertapenam used for in MRONJ?

Answer 26

Invanz/ertapenam = for patients with significant sclerosis who aren’t candidates for segmental resection.

• beta lactamase inhibitor and very broad spectrum > unasyn
• requires ID consult and picc line

Question 27

Is PRP useful for MRONJ?

Answer 27

Yes it is useful to promote soft tissue healing - but platelets may be compromised by chemotherapy making it less likely to be effective.

Likes to make splint with PRP as biologic dressing! and can’t hurt prognosis.

Question 28

Does Implant surgery increase risk of MRONJ?

Answer 28

Read with care - oral and IV BP use is not an absolute contraindication for dental implant placement

Question 29

What is AAOMS’s position on surgeries on patients taking antiresorptives?

Answer 29

Oral bp’s < 4 years = ok to do surgery

Oral bp’s > 4 years or with steroids = drug holiday of 2-3 months pre and post op.

IV bp’s should avoid surgery

Question 30

Fleischer implant protocol?

Answer 30

No drug holiday

If extraction heals with patient is probably OK for implant. Staged process. Extract - heal - graft - heal- implant - heal.

Cancer patients - only if it will improve oral function.

Avoid sclerotic areas - increase infection risk!

BMP is contraindicated in active cancer.