Osteonecrosis of the jaw
Medication related osteonecrosis of the jaw (MRONJ)
Common indications:
- osteoporosis
- cancer with bone metastasis (commonly breast, prostate, lung, renal, thyroid, bowel)
- cancer without metastasis
- multiple myeloma
- hypercalcaemia
Drug Names and formulations
- Zolendronate (Zometa/Aclasta) - IV
- Pamidronate (Pamidronate/Aredia) -IV
- Risedronate (Actonel/Atelvia) - oral
- Ibandronate (Bonviva) - oral & IV
- Alendronate (Alendronic Acid, Fosamax, Fosavance) - oral
- Clodronate (Loron 520, BoneFos) - oral
Overall MRONJ risk
- Oral: < 1%
- IV related to 6 monthly/yearly regime: 1-2%
- IV related to monthly regime: 1-16%
Risk factors associated with MRONJ
- Formulation: oral vs intravenous
- Duration/Number of infusions
- Invasive dental treatment e.g oral surgery
- Mandible > Maxilla
- Posterior jaw > Anterior jaw
- Immunosuppresion medication e.g corticosteroids, azathioprine, methotrexate
- Immunocompromised conditions e.g diabetes mellitus, HIV
- Additional medications: chemotherapy, anti-angiogencic medication (see others tab)
Common indications:
- osteoporosis
- cancer with bone metastasis (commonly breast, lung)
Drug Names and formulations
- Denosumab (Prolia, Xgeva) - subcutaneosus
Overall MRONJ risk
- IV related to 6 monthly/yearly regime: <1%
- IV related to monthly regime: 2-16%
Risk factors associated with MRONJ
- Formulation: oral vs intravenous
- Duration/Number of infusions
- Invasive dental treatment e.g oral surgery
- Mandible > Maxilla
- Posterior jaw > Anterior jaw
- Immunosuppresion medication e.g corticosteroids, azathioprine, methotrexate
- Immunocompromised conditions e.g diabetes mellitus, HIV
- Additional medications: previous bisphopshonate use, chemotherapy, anti-angiogencic medication (see others tab)
A number of other drugs have been implicated in MRONJ.
The risk of MRONJ is <1% in these drugs .
https://www.ncbi.nlm.nih.gov/pubmed/30713092
- Selective estrogen receptor modulator (SERM) - Raloxifene
- Radiopharmaceuticals - Radium 223
- Fusion Protein - Aflibercept
- Tyrosine Kinase Inhibitors - sunitinib, cabozantinib, imatinib, sorafenib, regorafenib, axitinib, pazopanib, dasatinib
- Monoclononal antibodies - bevacizumab, rituximab, adalimumab, ipilimumab, infliximab, romosozumab
- mammalian target of rapamycin (mTOR) - sirolimus, temsirolimus, everolimus
- Immunsuppressants - methotrexate, corticosteroids, thalidomide
Some of these drugs may be used in conjuction with bisphophonates and denosumab which will increase the risk of MRONJ
Osteoradionecrosis (ORN)
Each year around 7,800 new cases of mouth and oropharyngeal cancer are diagnosed in the UK. (Cancer Research UK)
Oropharyngeal cancer is on the rise the rise with the vast majority related to human papilloma virus (HPV)
A novel radiation delivery system (IMRT - intensity modulated radiation therapy) is now routinely used for head and neck radiotherapy
Head and neck radiotherapy can cause early and late effects such as:
- mucositis (inflammation of the mouth) and oral ulceration
- xerostomia (dry mouth)
- trismus (limited/stiff mouth opening)
- dysphagia (swallowing difficulties)
- neck fibrosis (neck stiffness/tightness)
- radiation caries (dental decay as a subsequence following radiotherapy)
- osteoradionecrosis
The subsite oral cavity and oropharyngeal cancer patients have the highest risk of ORN
ORN factors:
- Radiation delivery e.g external beam therapy, brachytherapy
- Radiation dose - Regions of the jaw recieivng >40Gy
- The additional use of chemotherapy
- Increasing time following completion of radiotherapy
- Dental interventions - e.g: extractions, infections
- Immunosuppresion medication e.g corticosteroids, azathioprine, methotrexate
- Immunocompromised conditions e.g diabetes mellitus, HIV
- Concomitant bisphosphonate use
- Human papilloma virus status
ORN prevention is the main focus and therefore a pre-radiotherapy assessment if key
Post-radiotherapy effects should be discussed
Good oral hygiene, regular dental attendance and smoking cessation (if applicable) should be encouraged
High fluoride toothpaste should be prescribed and considered as life long in those suffering from dry mouth
Dubious or poor prognosis teeth should be considered for dental extraction prior to radiotherapy
A mimimum of 10 days of healing is recommended for dental extraction before the commencement of radiation treatment
Additional teeth in areas of 'high risk' of ORN may also be considered for extraction to avoid the complication in the future from occuring
Regular dental check up should be maintained to avoided dental disease and the need for dental extractions
Routine dental treatment such as restorations (fillings), prosthesis (dentures), endodontics (roots canal treatment) and peridontal scaling (gum cleaning) are not risk factors for ORN and can be provided.
Dental extractions should be avoided if possible to reduce the risk of ORN
Dental implants carry the same risk as dental extractions for an indivudal tooth site
Not all extractions and all dental sites carry the same risk of developing ORN
There is no agreed concensus on the management of ORN
Numerous treatment modalities have been proposed with varying success. Multiple treatments may be used in conjunction. Those commonly used include:
- Antibiotics therapy - this treatment aims to help when the ORN area is infected.
- Surgery - there are various options within this category. This includes sequestrectomy (removal of sharp edges or loose bone fragments), debridement (smoothing and removing a dead bone in the region), resection & reconstruction (removing a large section of the jaw and rebuilding it with bone from elsewhere in the body)
- Hyperbaric oxygen therapy (HBOT) - This is not a sole treatment and is usually used to supplement ORN surgery or as prophylaxis for dental extraction after radiotherapy to reduce the risk of ORN. A recent UK study (HOPON trial) found HBOT did not provide any advantage in avoidance of ORN
- PENTOCLO (PENtoxifylline, TOcopherol, CLOdronate) - More recently the use of 3 medicines jointly has been proposed as a non-invasive medical management approach for ORN. A similar medical regime has also been used as prophylaxis for dental extraction after radiotherapy to reduce the risk of ORN. A recent retrospective case series highlighted potential promise.
