MRONJ Flashcards
Medical Indications for Bisphosphonates
- Osteoporosis
- Cancer treatment-induced bone loss
- Skeletal-related events in patients with malignancies that involve bone
- Giant cell tumor of bone
- Hypercalcemia of malignancy
- Paget disease of bone
Bisphosphonates are ____ absorbed in the GI tract
Poorly
Bisphosphonates are excreted _____ by the kidneys
Unchanged
Bisphosphonates have a high affinity for ______ within the bone
Hydroxyapatite
Bisphosphonates are ____ within the bone
Inactive
Bisphosphonates are released during ____ ____
Bone resorption
Bisphosphonates ____ osteoclast activity and ____ osteoclast apoptosis
Inhibit; promote
Two classes of bisphosphonates
Non-nitrogen containing BPs
Nitrogen containing BPs
Non-nitrogen containing BPs function
Osteoclast apoptosis
Nitrogen containing BPs: ____ mevalonate pathway and has ____ effects
Inhibits; antitumor
Nitrogen containing BPs: What three processes do these affect?
Affect osteoclastogenesis, apoptosis and cytoskeletal dynamics
Nitrogen containing BPs: Function of Zoledronate
- Inihibits human endothelial cell proliferation
- Modulates endothelial cell adhesion and migration
Denosumab/Prolia: Function
Acts against RANKL and inhibits osteoclast function
Function of Antiangiogenic medications
- Interfere with the formation of new blood vessels
- Used for various tumors/malignancies
Antiangiogenic Inhibitors:
Function of Tyrosine Kinase Inhibitors
-Reduce the blood supply to the tumor thereby impacting the tumor’s ability to grow.
“-nib”=
Tyrosine kinase Inhibitors
“-mab”=
Monoclonal antibody
Definition of MRONJ
Bone necrosis associated with pharmacologic therapies
First criteria to establish diagnosis of MRONJ
Current or previous treatment with BMA or angiogenic inhibitor
Second criteria to establish diagnosis of MRONJ
Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for longer than 8 weeks.
Third criteria to establish diagnosis of MRONJ
No history of radiation therapy to the jaws or metastatic disease to the jaws
MONJ can be caused by a _____ of bone resportion
Supression
MONJ can be caused by soft tissue ______
Toxicity
MONJ can be caused by ___-angiogenesis and subsequent _____ vascularity
Anti; decreased
MONJ can be caused by a local infection, with the presence of _______
Biofilm
MONJ can be caused by an exposure of the oral cavity to the _____ _____ through the teeth and PDL
Outside environment
High dose therapy for treatment of malignancy accounts for ___% of MRONJ cases
90%
The incidence of patients taking BP for osteoporosis is low, and 100 times lower with ____ patients
Cancer
What are the top two medical comorbidities leading to MRONJ
Chemotherapy and corticosteroids
What is the most common dental reason for MRONJ
Extractions
What are the two most offending meds leading to MRONJ
BPs and denosumab
A longer duration (>___ years) increases risk for MRONJ
2 years
Which route increases risk for MRONJ? IV or oral?
IV
What type of surgery is a major risk factor for MRONJ
Dentoalveolar surgery
Is the mandible or maxilla more at risk for MRONJ? Which parts specifically?
Mandible; mylohyoid ridge, lingual tori, palatal tori
There is a ___ fold increase in risk for developing MRONJ in patients receiving IV therapy for cancer and have inflammatory dental disease
7
What immune suppressing conditions increase risk for MRONJ?
Diabetes, autoimmune diseases, renal dialysis
What type of chemotherapeutic agents increase risk for MRONJ?
Corticosteroids, cyclophosphamde
What are two genetic factors that increase risk for MRONJ?
- Single nucleotide polymorphism in the cytochrome P450-2C gene
- MHC Class II polymorphism
MRONJ: Worse with ____ vs osteoporosis
Cancer
MRONJ: Worse with ___ meds vs. oral meds
IV
Stage 0 MONJ
- No clinical evidence of necrotic bone
- Nonspecific symptoms or clinical or radiographic findings present.
Stage 1 of MRONJ
- Exposed and necrotic bone present
- Asymptomatic with no evidence of infection
Stage 2 of MRONJ
Exposed and necrotic bone present
Painful and clinical evidence of infection
Stage 3 of MRONJ
Exposed and necrotic bone present.
Non-exposed bisphosphonate-related osteonecrosis of the jaw
- History of BP use
- Lack of bone exposure
- Deep periodontal pockets
- Drainage with or without sinus tracts
- Pain
- Advanced bone loss around involved teeth
- Radiographic involvement: osteolytic changes
What can a pano show with MRONJ?
Can identify sequestra
MRONJ: When is CT helpful?
Useful when MRONJ is suspected in the differential diagnosis; allows for 3D reconstruction
MRONJ: The CBCT has ____ radiation than CT
Less
MRONJ: MRI can detect what?
Histopathologic changes of necrotic bone
MRONJ: What are some goals for management?
Elimination of pain
Control infection
Reduce progression of bone necrosis
Prevent of reinfection
MRONJ: What procedure do we want to avoid if possible with active MRONJ?
Dental extractions
MRONJ: Stage 0 Suggested Treatment Strategy
- Patient education
- Systemic management, including the use of pain medication and antibotics
MRONJ: Stage 1 Suggested Treatment Strategy
- Antibacterial mouth rinses
- Clinical follow up on a quarterly basis
MRONJ: Stage 2 Suggested Treatment Strategy
- Patient education and review of indications for continued BP therapy
- Symptomatic treatment with oral antibotics.
MRONJ: Stage 3 Suggested Treatment Strategy
- Pain Control
- Debridement to relieve soft tissue irradiation and control the infection
- Antibacterial mouth rinse
- Antibiotic therapy and pain control
- Surgical debridement or resection for long-term palliation of infection and pain
Three ways to prevent MRONJ
- OHI
- Patient Education: MRONJ
- Dental Exam and Treatment
Prevention of quality of life with patients with MRONJ include
- Patient education and reassurance
- Control of pain
- Control of secondary infection
- Prevention of extension of lesion and development of new areas of necrosis
For patients initiating or receiving therapy for osteoporosis or a nonmalignant bone disorder for >3 years (low-dose therapy)
- Recommend non-surgical perio but modest bone recontouring may be done if needed
- Prefer endo vs extraction
- Dental implants are not contraindicated
For patients initiating or receiving therapy for a malignancy (high-dose therapy)
- Avoid elective surgical procedures
- Consider nonsurgical endo or perio therapy for symptomatic teeth
- Procedures that involve direct osseous injury should be avoided. non-restorable teeth may be treated by removal of crown and endodontic treatment of remaining roots
Treatment recommendation for those receiving oral antiresportive meds: Elective treatment is _____ contraindicated; what should we inform the patient of?
Not; small risk
There are ___ studies to show benefits of drug holidays in reducing MRONJ risk
No
Half life of BP drugs exceeds how many years
10
Treatment recommendation for those receiving oral antiresportive meds: What if I have to perform an extraction?
- Informed consent
- Atraumatic technique
- Primary closure
- use of semipermeable membrane
- CHX twice daily one week prior and continue afterwards depending on healing
- Consider administration of antibiotic beginning one day prior to ext extending until completion of 7-10 day course
Oral or IV BP use is not an absolute contraindicating to placing _____
Implants
Which biomarker stood out in assessing risk for developing MRONJ?
PTH
What is the CTX test?
A potential diagnostic blood test that could be used to predict risk for MRONJ
What is looked for in CTX test? Which marker?
C-terminal cross-linking telopeptide level in blood; the first marker
What is correlated in the CTX test?
The c-terminal cross-linking telopeptide and the osteoclastic activity with clinical healing or response to surgical debridement
How is the CTX test conducted
With the morning fasting blood test
What value indicates a high risk for oral MRONJ with the CTX test?
100 pg/ml or less
CTX Test Moderate risk value
100-150 pg/ml
CTX testing minimal risk
Greater than 150 pg/ml
FOr patients taking oral BP >3 years, get CTX:
If value is below 150, what should be done?
Drug holiday
After 4-6 months, repeat CTX
If still below 150 -> extend drug holiday
Rate of osteoclast activity averages ____ pg/ml per month
25
Level of CTX in blood recovers to value in excess of 150 pg/ml in how many months?
6 to 9 months