MRONJ and Chemo Flashcards
- Chemotherapy is administered before locoregional surgery or radiotherapy.
- Sequential therapy generally refers to chemotherapy followed by radiation with concurrent chemotherapy.
Neoadjuvant therapy or induction chemotherapy.
*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.
Chemotherapy
- Chemotherapy and radiotherapy are simultaneously administered after surgery in high‐risk patients, reducing metastatic burden.
Adjuvant therapy
- 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.
Concurrent chemoradiation for cure or organ preservation.
What is the most common type of chemotherapy agent?
Alkylating agents: cisplatin
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
Bisphosphonates
How do bisphosphonates work?
Prevent osteoclastic activity
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
Bisphosphonates ( non nitrogen)
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
Bisphosphonates (nitrogen containing)
Approved for use in the treatment of Paget’s disease
and osteoporosis
Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)
Oral nitrogen containing bisphosphonates
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
IV nitrogen containing bisphosphonates
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
Antiresorptive agents
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
Antiangiogenic meds
At what point does risk increase for someone taking antiresorptive or antiangiogenic meds?
18 months
After how long of taking an antiresorptive or antiangiogenic med does the risk of MRONJ persist for the rest of pt life?
5 years
__% increased risk of MRONJ with each passing decade
9%
What primary diagnosis has the highest risk for ONJ?
Multiple myeloma
Limit the amount of use
Place silicone liners if necessary (GC reline)
Educate the patient
3 month recall intervals
Removable appliances
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
3 month
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
Denosumab
What is the drug holiday recommended for denosumab?
2 months pre surg
4-8 months post surg
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
CTX testing
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
Dx of MRONJ
Stage ___ MRONJ
No exposed bone, but pt. is symptomatic
Radiographic changes may be present
Treatment
Periodic monitoring
Systemic management (antibiotics and pain meds)
Stage 0
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
Stage 1
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
Stage 2
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?
Stage 3
Resolve MRONJ in osteoporotic patients
May be used to treat osteoporosis
Contraindicated in pts. with bone metastases or
previous radiation (risk of osteogenic sarcoma)
Forteo
