MRONJ Flashcards
1
Q
what is chemotherapy used for
A
- head and neck squamous cell cancer for organ preservation in advanced disease
- may be used for palliative treatment as well as in combination with radiotherapy for postoperative high risk cases
2
Q
what are the 3 possible strategies for chemotherapy for HNSCC
A
- neoadjuvant therapy or induction chemotherapy
- adjuvant therapy
- concurrent chemoradiation for cure or organ preservation
3
Q
describe neoadjuvant therapy or induction chemotherapy
A
- chemotherapy is administered before locoregional surgery or radiotherapy
- sequential therapy generally refers to chemotherapy followed by radiation with concurrent chemotherapy
4
Q
describe adjuvant therapy
A
- chemotherapy and radiotherapy are simultaneously administered after surgery in high risk patients, reducing metastatic burden
5
Q
describe concurrent chemoradiation for cure or organ preservation
A
- simultaneous chemotherapy and radiotherapy are a definitive and curative treatment for instances in layrngeal 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
6
Q
what are the types of chemotherapy agents
A
- alkylating agents: cisplatin
- antibiotics- derivatives of antimicrobial compounds from streptomyces - doxorubicin, bleomycin, mitomycin
- antimetabolites: methotrexate and 5-fluorouracil
- alkaloids: vincristine or vinblastine
- taxanes: paclitaxel or docetaxel
7
Q
what are the types of chemotherapy agents
A
- bisphosphonates
- oral agents
- systemic agents
8
Q
what are bisphosphonates used for
A
management of malignancies in addition to systemic management of osteoporosis
9
Q
what are the antiresorptive medications
A
- bisphosphonates
- RANK ligand inhibitors
10
Q
what are bisphosphonates used to treat
A
osteoporosis
- paget’s disease
- osteogenesis imperfecta
- adjunctive cancer treatment
11
Q
what do bisphosphonates do
A
decrease osteoclastic activity
12
Q
describe non nitrogen bisphosphonates
A
- oral only: etidronate- didronel and clodronate- bonefos, clasteon, and loron
- primarily used for the treatment of Paget’s disease
- low potency
- prevents osteoclast proliferation by inhibiting ATP dependent enzymes
13
Q
describe nitrogen containing bisphosphonates and mechanism of action
A
- Oral or IV
- MOA: 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
14
Q
oral nitrogen containing bisphosphonates are approved to treat:
A
paget’s disease and osteoporosis
15
Q
what are the oral nitrogen containing bisphosphonates
A
- alendronate (Fosamax)
- risedronate (Actonel)
- Ibandronate (Bonvia)
16
Q
what are IV nitrogen containing bisphosphonates are used for and what drugs for each
A
- osteoporosis: zolendronate (Reclast) - 5mg/year
- bone metastases: zolendronate (Zometa)- 4mg/3 weeks and pamidronate (Aredia) - 90mg/3 weeks
17
Q
what are the antiresorptive agents
A
- denosumab (monoclonal antibody)
- osteoporosis - prolia - 60mg/6 months
- bone metastases - Xgeva - 120mg/4 weeks
18
Q
what is the MOA of antiresorptive agents
A
- 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 and prevents osteoclast proliferation
19
Q
what are the antiangiogenic medications
A
- tyrosine kinase inhibitor: sunitinib (Sutent) and Sorafenib (nexavar)
- humanized monoclonal antibody (bevacizumab (Avastin)
20
Q
what is the MOA of antiangiogenic medications
A
- recognizes and blocks vascular endothelial growth factor (VEGF) , a protein necessary for angiogenesis
21
Q
what are antiangiogenic medications used to treat
A
GI tumors, renal cell carcinomas, and neuroendocrine tumors
22
Q
what are the drug related risks for MRONJ
A
- oral non nitrogen containing bisphosphonates
- oral nitrogen containing bisphosphonates (0.4%-4%)
- IV bisphosphonates (4%-12%)- aredia and Zometa
- XGEVA
- IV bisphosphonates plus an antiangiogenic medication
23
Q
what is the duration of drug use that puts you at risk for MRONJ
A
increased risk after 18 months
24
Q
what are the local risk factors for MRONJ
A
- surgery/trauma: dental extractions, osseous surgery (periodontal, apicoectomy), implant placement
- anatomy: mandible vs maxilla (2:1 ratio), tori, exostoses, mylohyoid ridge
25
what are the demographic risk factors for MRONJ
- age: 9% increased risk of MRONJ with each passing decade
- race: caucasian
26
what are the systemic factors that are risk factors for MRONJ
- primary cancer diagnosis: multiple myeloma- highest risk
- breast cancer-2nd highest risk
- concurrent osteopenia or osteoporosis diagnosis
27
prior to starting antiresorptive medications:
- extract non restorable and questionable teeth along with alveoplasty, tori removal
- complete necessary periodontal therapy
- complete any endodontic and restorative work
28
what is the protocol for patients wearing removable appliances
- limit amount of use
- place silicone liners if necessary (GC reline)
- educate the patient
- 3 month recall intervals
29
while on antiresorptive/antiangiogenic agent therapy what should be done prior to therapy
any surgery or invasive procedure requires 3 month drug holiday prior to therapy and use of antiresorptive/antiangiogenic agents should not be started again until after osseous healing has occurred
30
how does Denosumab affect the body
- osteoclasts deceased by 85% in 3 days
- 1/2 life of denosumab is 25 days
- 80% degraded in 2 months
- denosumab only affects the RANK ligand
- not incorporated in the bone
31
describe the denosumab vacation
- 2 month presurgical holiday: 80% degradation
- average 4 month post surgical holiday (ideally 8 months)
- no needed alteration in denosumab therapy if planned correctly
32
how do you predict complications
CTX testing
33
what is CTX testing and what does it show
- measures serum levels of C-terminal telopeptide
- metabolite of bone matrix degradation
- marker for osteoclastic activity
- normal is greater than 300 (average 400-550)
- 150 or less is at risk for MRONJ
34
how do you avoid complications of MRONJ
- when there is significant risk of MRONJ or previous/current MRONJ present, avoid all surgical procedures if possible
- even if teeth are not restorable by traditional methods, roots can be retained by completing RTC and covering with composite or amalgam to avoid extraction
35
what 3 things are needed to dx MRONJ
- current or previous antiresorptive medication therapy
- exposed necrotic bone for longer than 8 weeks
- no history of radiation to the jaws
36
what is stage 0 and what is the treatmetn
- no exposed bone but pt is symptomatic
- radiographic changes may be present
- tx: systemic monitoring, systemic management (antibiotics and pain meds)
37
what is stage 1 and what is the tx
- bone is exposed, asymptomatic, no infection present
- tx: monitor closely for the first 8 weeks, if no change monitor every 3 months. meticulous home care. antimicrobial oral rinses such as peridex
38
what is stage 2 and what is the treatment
- exposed bone with associated pain and erythema
- purulent exudate may be present
- tx: same treatment as stage 1
- addition of systemic antibiotics (penicillin, clindamycin, doxycycline)
- pain management
- superficial debridement to relieve soft tissue irritation
39
what is stage 3 and what is the treatment
- 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
40
describe Forteo and who it is contraindicated in
- resolve MRONJ in osteoporotic patients
- may be used to treat osteoporosis
- contraindicated in pts with bone metastases or previous radiation (risk of osteogenic sarcoma)
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