MRONJ Flashcards
what is chemotherapy used for
- 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
what are the 3 possible strategies for chemotherapy for HNSCC
- neoadjuvant therapy or induction chemotherapy
- adjuvant therapy
- concurrent chemoradiation for cure or organ preservation
describe neoadjuvant therapy or induction chemotherapy
- chemotherapy is administered before locoregional surgery or radiotherapy
- sequential therapy generally refers to chemotherapy followed by radiation with concurrent chemotherapy
describe adjuvant therapy
- chemotherapy and radiotherapy are simultaneously administered after surgery in high risk patients, reducing metastatic burden
describe concurrent chemoradiation for cure or organ preservation
- 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
what are the types of chemotherapy agents
- 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
what are the types of chemotherapy agents
- bisphosphonates
- oral agents
- systemic agents
what are bisphosphonates used for
management of malignancies in addition to systemic management of osteoporosis
what are the antiresorptive medications
- bisphosphonates
- RANK ligand inhibitors
what are bisphosphonates used to treat
osteoporosis
- paget’s disease
- osteogenesis imperfecta
- adjunctive cancer treatment
what do bisphosphonates do
decrease osteoclastic activity
describe non nitrogen bisphosphonates
- 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
describe nitrogen containing bisphosphonates and mechanism of action
- 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
oral nitrogen containing bisphosphonates are approved to treat:
paget’s disease and osteoporosis
what are the oral nitrogen containing bisphosphonates
- alendronate (Fosamax)
- risedronate (Actonel)
- Ibandronate (Bonvia)
what are IV nitrogen containing bisphosphonates are used for and what drugs for each
- osteoporosis: zolendronate (Reclast) - 5mg/year
- bone metastases: zolendronate (Zometa)- 4mg/3 weeks and pamidronate (Aredia) - 90mg/3 weeks
what are the antiresorptive agents
- denosumab (monoclonal antibody)
- osteoporosis - prolia - 60mg/6 months
- bone metastases - Xgeva - 120mg/4 weeks
what is the MOA of antiresorptive agents
- 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
what are the antiangiogenic medications
- tyrosine kinase inhibitor: sunitinib (Sutent) and Sorafenib (nexavar)
- humanized monoclonal antibody (bevacizumab (Avastin)
what is the MOA of antiangiogenic medications
- recognizes and blocks vascular endothelial growth factor (VEGF) , a protein necessary for angiogenesis
what are antiangiogenic medications used to treat
GI tumors, renal cell carcinomas, and neuroendocrine tumors
what are the drug related risks for MRONJ
- 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
what is the duration of drug use that puts you at risk for MRONJ
increased risk after 18 months
what are the local risk factors for MRONJ
- surgery/trauma: dental extractions, osseous surgery (periodontal, apicoectomy), implant placement
- anatomy: mandible vs maxilla (2:1 ratio), tori, exostoses, mylohyoid ridge
what are the demographic risk factors for MRONJ
- age: 9% increased risk of MRONJ with each passing decade
- race: caucasian
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
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
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
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
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
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
how do you predict complications
CTX testing
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
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
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
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)
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
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
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
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)
