MRONJ and Chemo

Question 1

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

Answer 1

Neoadjuvant therapy or induction chemotherapy.

Question 2

*used primarily for Head and Neck Squamous Cell Cancer (HNSCC) for organ preservation in advanced disease
*may be used for palliative treatment as well as in combination with radiotherapy for postoperative high‐risk cases.

Answer 2

Chemotherapy

Question 3

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

Answer 3

Adjuvant therapy

Question 4

• Simultaneous chemotherapy and radiotherapy are a definitive and curative treatment for instances in laryngeal tumors.
• Radiation is used with cisplatin and 5‐fluorouracil 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 oropharynx.

Answer 4

Concurrent chemoradiation for cure or organ preservation.

Question 5

What is the most common type of chemotherapy agent?

Answer 5

Alkylating agents: cisplatin

Question 6

 Initially used for the treatment of osteoporosis,
Paget’s disease, and osteogenesis imperfecta
 More recently, they have been used as an
adjunctive treatment of cancer
 Decrease osteoclastic activity

Answer 6

Bisphosphonates

Question 7

How do bisphosphonates work?

Answer 7

Prevent osteoclastic activity

Question 8

 Oral only
 Etidronate –Didronel
 Clodronate –Bonefos, Clasteon, Loron
 Primarily used for the treatment of Paget’s disease
 Low potency
 Prevents osteoclast proliferation by inhibiting ATP
(adenine triphosphate) dependent enzymes

Answer 8

Bisphosphonates ( non nitrogen)

Question 9

 Oral or IV
 Mechanism of action
 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

Answer 9

Bisphosphonates (nitrogen containing)

Question 10

 Approved for use in the treatment of Paget’s disease
and osteoporosis
 Alendronate (Fosamax)
 Risedronate (Actonel)
 Ibandronate (Boniva)

Answer 10

Oral nitrogen containing bisphosphonates

Question 11

 Used in the treatment of osteoporosis
 Zolendronate (Reclast) –5mg/year
 Used in the treatment of bone metastases
 Zolendronate (Zometa) –4mg/3 weeks
 Pamidronate (Aredia) –90mg/3 weeks

Answer 11

IV nitrogen containing bisphosphonates

Question 12

 Denosumab (Monoclonal antibody)
 Osteoporosis –Prolia –60mg/6 months
 Bone Metastases –Xgeva –120mg/4 weeks
 Mechanism of action
 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

Answer 12

Antiresorptive agents

Question 13

 Tyrosine kinase inhibitor
 Sunitinib (Sutent)
 Sorafenib (Nexavar)
 Humanized monoclonal antibody
 Bevacizumab (Avastin)
 Mechanism of action
 Recognizes and blocks vascular endothelial growth
factor (VEGF), a protein necessary for angiogenesis
 Used in the treatment of gastrointestinal tumors,
renal cell carcinomas, and neuroendocrine tumors

Answer 13

Antiangiogenic meds

Question 14

At what point does risk increase for someone taking antiresorptive or antiangiogenic meds?

Answer 14

18 months

Question 15

After how long of taking an antiresorptive or antiangiogenic med does the risk of MRONJ persist for the rest of pt life?

Answer 15

5 years

Question 16

__% increased risk of MRONJ with each passing decade

Answer 16

9%

Question 17

What primary diagnosis has the highest risk for ONJ?

Answer 17

Multiple myeloma

Question 18

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

Answer 18

Removable appliances

Question 19

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 19

3 month

Question 20

 Osteoclasts decreased by 85% in 3 days
 ½ life is 25 days
 80% degraded in 2 months
 only affects the RANK ligand
 Not incorporated in the bone

Answer 20

Denosumab

Question 21

What is the drug holiday recommended for denosumab?

Answer 21

2 months pre surg
4-8 months post surg

Question 22

 Measures serum levels of C-terminal telopeptide
 Metabolite of bone matrix degradation
 Marker for osteoclastic activity
 Normal is >300 (average 400-550)
 150 or less is at risk for MRONJ

Answer 22

CTX testing

Question 23

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

Answer 23

Dx of MRONJ

Question 24

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

Answer 24

Stage 0

Question 25

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

Answer 25

Stage 1

Question 26

 Stage ___ MRONJ
 Exposed bone with associated pain and erythema
 Purulent exudate may be present
 Treatment:
 Monitor closely for the first 8 weeks
 If no change, monitor every 3 months
 Meticulous home care
 Antimicrobial oral rinses
 Peridex
 Addition of systemic antibiotics(Penicillin, Clindamycin,
Doxycycline)
 Pain Management
 Superficial debridement to relieve soft tissue irritation

Answer 26

Stage 2

Question 27

 Stage ___ MRONJ
 Exposed bone with pain and one of the following:
 Pathologic fracture
 Extra-oral fistula
 Necrotic lesion extends to the inferior border
 Treatment:
 Surgical debridement or resection
 Antibiotic therapy
 Possible hyperbaric oxygen?

Answer 27

Stage 3

Question 28

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

Answer 28

Forteo