Bisphosphonates Flashcards
What are the types of drugs that increase risk of MRONJ?
- Anti-resorptive drugs - bisphosphonates or denosumab
- Anti-angiogenic drugs - bevacizumab or sunitinib
What is MRONJ?
Medication Related Osteonecrosis of the Jaw
exposed bone that has persisted for more than 8 weeks
What are the symptoms of MRONJ?
- swelling
- numbness
- pain
- altered taste or sensation
- signs of infection
What are the signs of MRONJ?
- delayed healing following extraction
- Exposed bone
- soft tissue infection
What are the risk factors for MRONJ?
- medical conditions affecting bone turnover (e.g. osteoporosis)
- malignancy
- chemotherapy/radiotherapy
- Previous diagnosis of MRONJ
- antiresorptive or antiangiogenetic drugs
- Duration of drug treatment
- concurrent treatment with systemic glucocorticoids
What is indicative of high risk for MRONJ?
- previous diagnosis of MRONJ
- if the patient is taking anti-resorptive or anti-angiogenic drugs
- undergoing cancer treatment
- if the patient was/is taking RANKL inhibitor (denosumab) AND steroids
- If the patient has been taking/ has taken bisphosphonates for 5 years or more
How do anti-resorptive drugs work?
they inhibit osteoclast differentiation and function, leading to decreased bone resorption and remodelling
What is the function of bisphosphonates?
They inhibit osteoclast formation decreasing bone resorption
Bisphosphonates have a high affinity for bone minerals and bind strongly to hydroxyapatite in bone
They persist for a period of time (half life of 10 years)
How does bisphosphonates affect soft tissues ?
They inhibit proliferation and increase apoptosis which can lead to delayed soft tissue healing
What conditions are treated by bisphosphonates?
non malignant conditions - Osteoporosis and Paget’s disease
malignant conditions - myeloma and breast cancer
What type of drug is Denosumab?
A Monoclonal Antibody
What is the function of Denosumab?
it inhibits osteoclast function and associated bone resorption by binding to RANKL
What conditions are treated by Denosumab?
- osteoporosis
- metastatic disease (cancer)
What is an advantage of Denosumab compared to a bisphosphonate?
it does not bind to bone so its effect on bone turnover diminish within 9 months of treatment completion
How do anti-angiogenic drugs work?
they target the processes which create new blood vessels
they are used in cancer treatment to restrict tumour vascularisation
What three anti-angiogenic drugs are associated with MRONJ risk?
bevacizumab - vascular endothelial growth factor inhibitor (VEGF)
aflibercept - VEGF inhibito
sunitinib - receptor tyrosine kinase (RTK) inhibitor
What conditions in children are treated by bisphosphonates?
- osteogenesis imperfecta
- fibrous dysplasia
- crohn’s disease
- bone dysplasia
- juvenile osteoposrosis
- rheumatologic disorders
Why is temporarily stopping bisphosphonates not successful in reducing MRONJ risk?
the drug persists in the skeletal tissue for years after due to long half life
What risk group for MRONJ are patient being treated for cancer?
High Risk
What risk group for MRONJ are patients taking bisphosphonates for <5 years?
Lower Risk
What risk group for MRONJ are patients taking denosumab
Lower risk
What risk group for MRONJ are patients that took denosumab > 9 months ago with no systemic glucocorticoids
Lower risk
What risk group for MRONJ are patients taking denosumab and concurrent systemic glucocorticoids?
High Risk
What risk group for MRONJ are patient taking bisphosphonates for > 5 years?
High Risk
What risk group for MRONJ are patient taking bisphosphonates for < 5 years and taking systemic glucoscorticosteroids?
High Risk
What risk group for MRONJ are patients who have previously had MRONJ?
High Risk
How do you assess MRONJ risk in patients who previously took bisphosphonates?
Assess as though they are still taking the medication and determine risk from duration of medication
If a patient has MRONJ who do you refer them to?
Oral surgery
OR
Special care dentistry
What are the key elements of a treatment plan for patients at risk of MRONJ?
Ideally make patients dentally fit before medications starts
Extraction is a last resort - try every other option first
Prevention is essential to prevent future treatment
What are modifiable factors to reduce risk of MRONJ?
- oral hygiene
- smoking
- alcohol consumption
- diet
