MRONJ

Question 1

Chemotherapy for Oral Malignancies
* used primarily for …
* may be used for …

Answer 1

Head and Neck
Squamous Cell Cancer (HNSCC) for organ
preservation in advanced disease

palliative treatment as well
as in combination with radiotherapy for
postoperative high‐risk cases.

Question 2

Chemotherapy for HNSCC
Three possible strategies.

Answer 2

1. Neoadjuvant therapy or induction chemotherapy.
2. Adjuvant therapy
3. Concurrent chemoradiation for cure or organ preservation.

Question 3

1. Neoadjuvant therapy or induction chemotherapy.
   (2)

Answer 3

• Chemotherapy is administered before locoregional surgery or
  radiotherapy.
• Sequential therapy generally refers to chemotherapy followed by
  radiation with concurrent chemotherapy.

Question 4

2. Adjuvant therapy

Answer 4

• Chemotherapy and radiotherapy are
  simultaneously administered after surgery in
  high‐risk patients, reducing metastatic
  burden

Question 5

3. Concurrent chemoradiation for cure or organ preservation.
   * Simultaneous (2) are a definitive and
   curative treatment for instances in – tumors.
   * Radiation is used with (2) for the additive (or
   supra‐additive) radiosensitizing effect of chemotherapy to enhance the
   effectiveness of the radiation treatment.
   * considered a standard of care for tumors of the —.

Answer 5

chemotherapy and radiotherapy
laryngeal
cisplatin and 5‐fluorouracil
oropharynx

Question 6

Types of chemotherapy agents
(5)

Answer 6

• Alkylating agents
• Antibiotics
• Antimetabolites
• Alkaloids
• Taxanes

Question 7

• Alkylating agents
  (1)

Answer 7

• cisplatin;

Question 8

• Antibiotics—
  (3)

Answer 8

derivatives of antimicrobial compounds from Streptomyces
eg. doxorubicin,
bleomycin
mitomycin

Question 9

• Antimetabolites
  (2)

Answer 9

• methotrexate
• 5‐fluorouracil;

Question 10

• Alkaloids
  (2)

Answer 10

• vincristine
• vinblastine;

Question 11

• Taxanes
  (2)

Answer 11

• paclitaxel
• docetaxel

Question 12

Types of chemotherapy agents
Bisphosphonates – being used more for management of
— in addition to systemic management of
osteoporosis

Answer 12

malignancies

-
Systemic agents
-
-

Question 13

 Antiresorptive Medications
(2)
 Antiangiogenic Medications

Answer 13

 Bisphosphonates
 RANK Ligand Inhibitors

Question 14

Bisphosphonates
 Initially used for the treatment of (3)
 More recently, they have been used as an
adjunctive treatment of —
 Decrease — activity

Answer 14

osteoporosis,
Paget’s disease, and osteogenesis imperfecta
cancer
osteoclastic

Question 15

Bisphosphonates (Non-Nitrogen)
 Oral only
(2)
 Primarily used for the treatment of —
 — potency
 Prevents …

Answer 15

 Etidronate – Didronel
 Clodronate – Bonefos, Clasteon, Loron

Paget’s disease
Low
osteoclast proliferation by inhibiting ATP
(adenine triphosphate) dependent enzymes

Question 16

Bisphosphonate
(Nitrogen Containing)
 (2)
 Mechanism of action
(2)

Answer 16

Oral or IV

 Prevents binding of essential proteins to the cell
membrane leading to apoptosis
 Prevents adhesion of the osteoclasts to the
hydroxyapatite crystals by altering the cell cytoskeleton

Question 17

Oral Nitrogen Containing
Bisphosphonates
 Approved for use in the treatment of (2)

ex (3)

Answer 17

Paget’s disease
and osteoporosis

 Alendronate (Fosamax)
 Risedronate (Actonel)
 Ibandronate (Boniva)

Question 18

IV Nitrogen Containing
Bisphosphonates
 Used in the treatment of osteoporosis
(1)
 Used in the treatment of bone metastases
(1)

Answer 18

 Zolendronate (Reclast) – 5mg/year

 Zolendronate (Zometa) – 4mg/3 weeks
 Pamidronate (Aredia) – 90mg/3 weeks

Question 19

Antiresorptive Agents
 Denosumab (Monoclonal antibody)
 Osteoporosis –
 Bone Metastases –
 Mechanism of action
(2)

Answer 19

Prolia – 60mg/6 months
Xgeva – 120mg/4 weeks

 Tumor cell promote the release of RANK Ligand from
the osteoblast with in turn promote the production of
osteoclasts
 Denosumab binds to the RANK Ligand an prevents
osteoclast proliferation
Antiresorptive Agents

Question 20

ANTIANGIOGENIC MEDICATIONS
(2)

Answer 20

 Tyrosine kinase inhibitor
 Humanized monoclonal antibody

Question 21

 Tyrosine kinase inhibitor
(2)

Answer 21

 Sunitinib (Sutent)
 Sorafenib (Nexavar)

Question 22

 Humanized monoclonal antibody
(1)

Answer 22

 Bevacizumab (Avastin)
ANTIANGIOGENIC MEDICATIONS

Question 23

ANTIANGIOGENIC MEDICATIONS
 Mechanism of action
(1)
 Used in the treatment of (3)

Answer 23

 Recognizes and blocks vascular endothelial growth
factor (VEGF), a protein necessary for angiogenesis

gastrointestinal tumors,
renal cell carcinomas,
and neuroendocrine tumors

Question 24

Drug Related Risks
 Potency
(5)
 Duration
 Increased risk after —

Answer 24

 Oral non-nitrogen containing bisphosphonates
 Oral nitrogen containing bisphosphonates (0.4% to 4%)
 IV bisphosphonates (4% to 12%)
- Aredia
- Zometa
 XGEVA
 IV bisphosphonates plus an antiangiogenic medication

18 months

Question 25

Local Risk Factors  Surgery/trauma (3)

Answer 25

 Dental extractions  Osseous surgery (periodontal, apicoectomy)  Implant placement

Question 26

Local Risk Factors  Anatomy (3)

Answer 26

 Mandible vs. Maxilla (2:1 ratio)  Tori, exostoses  Mylohyoid ridge

Question 27

Demographic Factors  Age (1)  Race (1)

Answer 27

 9% increased risk of MRONJ with each passing decade  Caucasian

Question 28

Systemic Factors  Primary cancer diagnosis (2)  Concurrent (2) diagnosis

Answer 28

 Multiple myeloma – highest risk  Breast cancer – 2nd highest risk osteopenia or osteoporosis

Question 29

Prior to starting therapy (3)

Answer 29

 Extract non-restorable and questionable teeth along with alveoplasty, tori removal, etc.  Complete necessary periodontal therapy  Complete any endodontic and restorative work

Question 30

Wearing Removable Appliances (4)

Answer 30

 Limit the amount of use  Place silicone liners if necessary (GC reline)  Educate the patient  3 month recall intervals

Question 31

While on Antiresorptive/Antiangiogenic Agent Therapy If any surgery or invasive procedures are necessary, a -- month “drug holiday” should be completed prior to therapy and use of the antiresorptive/antiangiogenic agents should not be started again until after osseous healing has occurred

Answer 31

3

Question 32

Denosumab and the Body  Osteoclasts decreased by --% in 3 days  ½ life of denosumab is -- days  --% degraded in 2 months  Denosumab only affects the ...

Answer 32

85 25 80 RANK ligand  Not incorporated in the bone

Question 33

The Denosumab Vacation  2 month presurgical holiday (1)  Average 4 month postsurgical holiday (ideally 8 months) (1)

Answer 33

 80% degradation  No needed alteration in denosumab therapy if planned correctly

Question 34

Predicting Complications? CTX testing  Measures serum levels of ---  Marker for --- activity  Normal is ---  --- or less is at risk for MRONJ

Answer 34

C-terminal telopeptide osteoclastic >300 (average 400-550) 150

Question 35

 Measures serum levels of C-terminal telopeptide (1)

Answer 35

 Metabolite of bone matrix degradation

Question 36

AVOIDING COMPLICATIONS  If possible, when there is a significant risk for MRONJ or previous/current MRONJ present, avoid all --- if possible  Even if teeth are not restorable by traditional methods, roots can be retained by ...

Answer 36

surgical procedures completing RTC and covering with composite or amalgam to avoid extraction

Question 37

Diagnosis of MRONJ 3 things necessary (3)

Answer 37

 Current or previous antiresorptive medication therapy  Exposed necrotic bone for longer than 8 weeks  No history of radiation to the jaws

Question 38

If MRONJ is present:  Stage 0 (2)  Treatment (2)

Answer 38

 No exposed bone, but pt. is symptomatic  Radiographic changes may be present  Periodic monitoring  Systemic management (antibiotics and pain meds)

Question 39

If MRONJ is present:  Stage 1: (1)  Treatment: (3)

Answer 39

 Bone is exposed, asymptomatic, no infection present  Monitor closely for the first 8 weeks - If no change, monitor every 3 months  Meticulous home care  Antimicrobial oral rinses - Peridex

Question 40

If MRONJ is present:  Stage 2: (1)  Treatment: (3)

Answer 40

 Exposed bone with associated pain and erythema  Purulent exudate may be present  Same treatment as Stage 1 - Addition of systemic antibiotics(Penicillin, Clindamycin, Doxycycline)  Pain Management  Superficial debridement to relieve soft tissue irritation

Question 41

If MRONJ is present:  Stage 3:  Exposed bone with pain and one of the following: (3)  Treatment: (3)

Answer 41

 Pathologic fracture  Extra-oral fistula  Necrotic lesion extends to the inferior border  Surgical debridement or resection  Antibiotic therapy  Possible hyperbaric oxygen?

Question 42

Forteo (3)

Answer 42

 Resolve MRONJ in osteoporotic patients  May be used to treat osteoporosis  Contraindicated in pts. with bone metastases or previous radiation (risk of osteogenic sarcoma)