Management of patients at Risk of Medication-Related Osteonecrosis of Jaw Flashcards
What does MRONJ stand for?
- Medication related osteonecrosis of the jaw
What is MRONJ?
- Rare side effect of anti-resorptive and anti-angiogenic drugs
- Exposed bone or bone that can be probed through an intraoral or extraoral fistula in maxillofacial region that has persisted more than 8 weeks
What are the signs and symptoms of MRONJ?
- Delayed healing following dental extraction or other oral surgery
- Pain
- Soft tissue infection or swelling
- Numbness
- Paraesthesia
- Exposed bone
What are the current hypotheses of MRONJ mechanisms?
- Suppression of bone turnover
- Inhibition of angiogenesis
- Toxic effects on soft tissues, inflammation or infection
- Likely cause is multifactorial with both genetic and immunological elements
What are the risk factors for MRONJ?
- Underlying medical condition :
- cancer
- osteoporosis
- Cumulative drug dose (and duration of drug treatment)
- Concurrent treatment with systemic glucocorticoids
- Dentoalveolar surgery and mucosal trauma
How do anti-resorptive drugs work?
- Osteoclasts break down (resorb) bone tissue
- Inhibit osteoclast differentiation and function
- Leads to decreased bone resorption and remodelling
What anti-resorptive drugs have been linked to MRONJ and what are they used for?
- Bisphosphonates
- Denosumab
- Used for management of osteoporosis and other non malignant and malignant conditions
How do bisphosphonates work?
- Reduce bone resorption
/ - high affinity for hydroxyapatite of bone and persist in skeletal tissue for a long time
- ingested by osteoclast
- inhibiting enzymes essential to formation, recruitment and function of osteoclasts
What is the half life of alendronate?
- Approx 10 years
What are bisphosphonates used for(conditions)?
- Reduce symptoms and complications of metastatic bone disease (breast cancer, prostate cancer and multiple myeloma) - high dose Intravenous
- Osteoporosis
- Paget’s disease
- Osteogenesis imperfecta
- Fibrous dysplasia
What is denosumab?
-
Human monoclonal antibody
/ - Acts like OPG- RANKL inhibitor
- Binds to RANKL
- So that it can’t bind to RANK
- Inhibits osteoclast function and associated bone resorption
( RANKL binding to RANK on osteoclast precursor to promotes the differentiation and maturation of osteoclast)
What is denosumab used for?
- Prophylaxis and treatment of osteoporosis
- Subcutaneously every 6 months for osteoporosis
/ - Reduce SKE skeletal -related events related to metastasis ( breast cancer etc)
- Higher dose monthly in metastatic disease
/ - Effects on bone turnover diminish within 9months after treatment completion
What are anti-angiogenic drugs?
- Target the processes by which new blood vessels formed
- Used in cancer treatment to restrict tumour revascularisation
what are some types anti-angiogenic drugs related to MRONJ?
- Vascular endothelial growth factor (VEGF) inhibitors:
- bevacizumab
- and aflibercept
/ - Receptor tyrosine kinase inhibitor
- sunitinib
What are bisphosphonates used for in children?
- Osteogenesis imperfecta
- Fibrous dysplasia
- Neuromuscular disorders
- Bone dysplasia
- Idiopathic juvenile osteoporosis
- Rheumatologic disorders
- Crohn’s disease
What is considered low risk of patient getting MRONJ?
- Patient treated for osteoporosis or other non-malignant diseases of bone (Paget’s disease) with oral bisphosphonates for less than 5 years and not concurrently treated with systemic glucocorticoids
- Patient treated for osteoporosis or other non-malignant diseases of bone (Paget’s disease) with quarterly or yearly IV infusions bisphosphonates for less than 5 years and not concurrently treated with systemic glucocorticoids
- Treated with denosumab and not being treated with systemic glucocorticoids
What is considered a high risk patient of MRONJ?
- Patients being treated for osteoporosis or other non-malignant disease of bone with oral or IV infusions of bisphosphonates more than 5 years
- Patients on bisphosphonates or denosumab for any length of time if concurrently treated with systemic glucocorticoids
- Patients treated with anti-resorptive or anti-angiogenic drugs (or both) as part of management of cancer
- Patients with previous diagnosis of MRONJ
What questions can you ask a patient to prompt them if the drug is anti-resorptive or anti-angiogenic?
- Have you ever been prescribed medicine for you bones?
- Do you take medicine once a week?
- Have you ever had drug infusion for your bones?
- Do you take long-term steroids for any condition?
What is the key recommendation for **treatment plan **of patients before commencement of anti-resorptive or anti-angiogenic drug therapy?
- Aim to get patient as **dentally fit as feasible **
- Prioritise preventative care
- Higher risk cancer patients undergo a thorough dental assessment
What is the advice you should give to patient about to commence anti-resorptive or anti-angiogenic drugs or those who have recently started?
- Advise patient that due to medication they are at risk of developing MRONJ but risk is small
- Don’t discourage form taking the medication or undergoing dental treatment
- Record advise
- Healthy diet and reduce sugary snack and drinks
- Maintain excellent oral hygiene
- Using fluoride toothpaste and mouthwash
- Stop smoking
- Limiting alcohol intake
- Regular dental checks
- Report an symptoms such as exposed bone, loose teeth, non-healing sores or lesions, pus or discharge, tingling, numbness or altered sensations, pain or swelling as soon as poss
What are some examples of care you can do that will reduce mucosal trauma or help avoid future extractions or any oral surgery that may impact bone?
- Use appropriate radiographs to identify possible areas of infection and pathology
- Undertake any remedial dental work
- Extract any teeth of poor prognosis without delay
- Focus on minimising periodontal/dental infection or disease
- Adjust or replace** poorly fitting dentures** to minimise future mucosal trauma
- Consider prescribing high fluoride toothpaste
What to do for low risk patient if they require extraction and have been made as dentally fit as feasible?
- Discuss risks and benefits
- Proceed with treatment as clinically indicated
- Don’t prescribe antibiotic or antiseptic prophylaxis unless required for other clinical reasons
- Advise patient to contact practice if any concerns like unexpected tingling, pain, numbness, altered sensation or swelling in extraction area
- Review healing
- If extraction not healed in 8 weeks and suspect MRONJ = Refer to special care dentistry/oral surgery
- Reporting to **yellow card scheme **and encourage patient to as well
What are some bisphosphonates and their indication?
Alendronic acid = Binosto = Osteoporosis
/
Risedronate sodium = Actonel = Osteoporosis / Paget’s disease
/
Zoledronic acid = Aclasta = Osteoporosis/ Paget’s disease/ Treatment of cancer
/
Ibandronic acid = Osteoporosis/ Treatment of cancer
/
Pamidronate disodium = Paget’s disease/ Bone pain/ Treatment of cancer
/
Sodium clodronate = Bone pain/ Treatment of cancer
What is the RANKL inhibitors and their indication?
Denosumab = Prolia = Osteoporosis/ Treatment of cancer
What are some anti-angiogenic drugs and their indication?
Bevacizumab = avastin = Treatment of cancer
Sunitinib = Sutent = Treatment of cancer
Aflibercept = Zaltrap = Treatment of cancer
What can you do before treatment for medically complex patients?
- Consider** seeking advice** from oral surgery/ special care dentistry specialist with regard to clinical assessment , treatment planning and ongoing management
What are the benefits of anti-resorptive or anti-angiogenic drugs and why should the patient not stop the drugs?
- Anti-resorptive drugs reduce risk of fractures and subsequent chronic pain in pts treated for osteoporosis
- Anti-angiogenic drugs restrict growth of tumour blood vessels and important in some cancer treatments/ Reduce bone pain and risk of fractures
- **Drug holidays **not recommended as drugs benefits likely to outweigh risk of MRONJ and in case of bisphosphantes and denosumab it doesn’t affect risk
