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 the patient is being treated for
- Cumulative drug dose (and duration of drug treatment)
- Concurrent treatment with systemic glucocorticoids
- Dentoalveolar surgery and mucosal trauma
- Cancer patients
- Osteoporosis patients being treated with oral anti-resorptive drugs
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
- Delays onset of disease or treatment complications like bone fractures and bone pain
How do bisphosphonates work?
- Reduce bone resorption by inhibiting enzymes essential to formation, recruitment and function of osteoclasts
- Have high affinity for hydroxyapatite and persist in skeletal tissue for sig length of time
What is the half life of alendronate?
- Approx 10 years
What are bisphosphonates used for?
- 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
- Inhibits osteoclast function and associated bone resorption
- By binding to receptor activator nuclear factor kB ligand (RANKL)
What is denosumab used for?
- Prophylaxis and treatment of osteoporosis
- Reduce skeletal -related events related to metastasis ( breast cancer etc)
- Subcutaneously every 6 months for osteoporosis
- 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
How are some 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?
- 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 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
- Stopping 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
