MRONJ Flashcards
Chemotherapy for Oral Malignancies
* used primarily for …
* may be used for …
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.
Chemotherapy for HNSCC
Three possible strategies.
- Neoadjuvant therapy or induction chemotherapy.
- Adjuvant therapy
- Concurrent chemoradiation for cure or organ preservation.
- Neoadjuvant therapy or induction chemotherapy.
(2)
- Chemotherapy is administered before locoregional surgery or
radiotherapy. - Sequential therapy generally refers to chemotherapy followed by
radiation with concurrent chemotherapy.
- Adjuvant therapy
- Chemotherapy and radiotherapy are
simultaneously administered after surgery in
high‐risk patients, reducing metastatic
burden
- 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 —.
chemotherapy and radiotherapy
laryngeal
cisplatin and 5‐fluorouracil
oropharynx
Types of chemotherapy agents
(5)
- Alkylating agents
- Antibiotics
- Antimetabolites
- Alkaloids
- Taxanes
- Alkylating agents
(1)
- cisplatin;
- Antibiotics—
(3)
derivatives of antimicrobial compounds from Streptomyces
eg. doxorubicin,
bleomycin
mitomycin
- Antimetabolites
(2)
- methotrexate
- 5‐fluorouracil;
- Alkaloids
(2)
- vincristine
- vinblastine;
- Taxanes
(2)
- paclitaxel
- docetaxel
Types of chemotherapy agents
Bisphosphonates – being used more for management of
— in addition to systemic management of
osteoporosis
malignancies
-
Systemic agents
-
-
Antiresorptive Medications
(2)
Antiangiogenic Medications
Bisphosphonates
RANK Ligand Inhibitors
Bisphosphonates
Initially used for the treatment of (3)
More recently, they have been used as an
adjunctive treatment of —
Decrease — activity
osteoporosis,
Paget’s disease, and osteogenesis imperfecta
cancer
osteoclastic
Bisphosphonates (Non-Nitrogen)
Oral only
(2)
Primarily used for the treatment of —
— potency
Prevents …
Etidronate – Didronel
Clodronate – Bonefos, Clasteon, Loron
Paget’s disease
Low
osteoclast proliferation by inhibiting ATP
(adenine triphosphate) dependent enzymes
Bisphosphonate
(Nitrogen Containing)
(2)
Mechanism of action
(2)
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
Oral Nitrogen Containing
Bisphosphonates
Approved for use in the treatment of (2)
ex (3)
Paget’s disease
and osteoporosis
Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)
IV Nitrogen Containing
Bisphosphonates
Used in the treatment of osteoporosis
(1)
Used in the treatment of bone metastases
(1)
Zolendronate (Reclast) – 5mg/year
Zolendronate (Zometa) – 4mg/3 weeks
Pamidronate (Aredia) – 90mg/3 weeks
Antiresorptive Agents
Denosumab (Monoclonal antibody)
Osteoporosis –
Bone Metastases –
Mechanism of action
(2)
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
ANTIANGIOGENIC MEDICATIONS
(2)
Tyrosine kinase inhibitor
Humanized monoclonal antibody
Tyrosine kinase inhibitor
(2)
Sunitinib (Sutent)
Sorafenib (Nexavar)
Humanized monoclonal antibody
(1)
Bevacizumab (Avastin)
ANTIANGIOGENIC MEDICATIONS
ANTIANGIOGENIC MEDICATIONS
Mechanism of action
(1)
Used in the treatment of (3)
Recognizes and blocks vascular endothelial growth
factor (VEGF), a protein necessary for angiogenesis
gastrointestinal tumors,
renal cell carcinomas,
and neuroendocrine tumors
Drug Related Risks
Potency
(5)
Duration
Increased risk after —
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
Local Risk Factors
Surgery/trauma
(3)
Dental extractions
Osseous surgery (periodontal, apicoectomy)
Implant placement
Local Risk Factors
Anatomy
(3)
Mandible vs. Maxilla (2:1 ratio)
Tori, exostoses
Mylohyoid ridge
Demographic Factors
Age
(1)
Race
(1)
9% increased risk of MRONJ with each passing decade
Caucasian
Systemic Factors
Primary cancer diagnosis
(2)
Concurrent (2) diagnosis
Multiple myeloma – highest risk
Breast cancer – 2nd highest risk
osteopenia or osteoporosis
Prior to starting therapy
(3)
Extract non-restorable and questionable teeth along
with alveoplasty, tori removal, etc.
Complete necessary periodontal therapy
Complete any endodontic and restorative work
Wearing Removable Appliances
(4)
Limit the amount of use
Place silicone liners if necessary (GC reline)
Educate the patient
3 month recall intervals
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
3
Denosumab and the Body
Osteoclasts decreased by –% in 3 days
½ life of denosumab is – days
–% degraded in 2 months
Denosumab only affects the …
85
25
80
RANK ligand
Not incorporated in the bone
The Denosumab Vacation
2 month presurgical holiday
(1)
Average 4 month postsurgical holiday (ideally 8
months)
(1)
80% degradation
No needed alteration in denosumab therapy if planned
correctly
Predicting Complications?
CTX testing
Measures serum levels of —
Marker for — activity
Normal is —
— or less is at risk for MRONJ
C-terminal telopeptide
osteoclastic
>300 (average 400-550)
150
Measures serum levels of C-terminal telopeptide
(1)
Metabolite of bone matrix degradation
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 …
surgical procedures
completing RTC
and covering with composite or amalgam to avoid
extraction
Diagnosis of MRONJ
3 things necessary
(3)
Current or previous antiresorptive medication therapy
Exposed necrotic bone for longer than 8 weeks
No history of radiation to the jaws
If MRONJ is present:
Stage 0
(2)
Treatment
(2)
No exposed bone, but pt. is symptomatic
Radiographic changes may be present
Periodic monitoring
Systemic management (antibiotics and pain meds)
If MRONJ is present:
Stage 1:
(1)
Treatment:
(3)
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
If MRONJ is present:
Stage 2:
(1)
Treatment:
(3)
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
If MRONJ is present:
Stage 3:
Exposed bone with pain and one of the following:
(3)
Treatment:
(3)
Pathologic fracture
Extra-oral fistula
Necrotic lesion extends to the inferior border
Surgical debridement or resection
Antibiotic therapy
Possible hyperbaric oxygen?
Forteo
(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)
