What is the diagnostic criteria for the MRONJ?
The definition and diagnostic criteria for this condition require that all four criteria be met: the patient must have current or previous treatment with antiresorptive or antiangiogenic agents; there must be exposed bone, or bone that can be probed through a fistula in the maxillofacial region; the exposed or probed bone must have persisted for at least 8 weeks; and there should be no history of radiation therapy to the jaw or metastatic disease involving the jaw.
What are anti-resorptive drugs?
Antiresorptive drugs inhibit osteoclastic activity and come in two main types: bisphosphonates and Denosumab (a RANK-L inhibitor). Bisphosphonates, such as Alendronate, Risedronate, and Zoledronic acid, work by impairing osteoclastic bone resorption and promoting osteoclast apoptosis. They bind to hydroxyapatite in the bone, leading to a long-term effect even after the treatment is stopped. Denosumab targets the RANK receptor on pre-osteoclasts, which, when bound by RANK ligand on osteoblast surfaces, promotes osteoclast differentiation, activity, and survival. Denosumab blocks RANK-L from binding to pre-osteoclasts, reducing osteoclast numbers and activity; however, since it does not bind to bone, its effects diminish within six months. These drugs are used to treat osteoporosis, Paget’s disease, and certain cancer-related conditions, including hypercalcemia and skeletal-related events.
Although medication - related osteonecrosis of the jaw has significant consequences for the patient and can be difficult to treat the benefits of antiresorptive therapy outweight the risk of harm in most patients. |
What are antiangiogenic drugs?
Antiangiogenic drugs (e.g. beavacizumab, sunitinib, zoledronic acid) interfere with the formation of new blood vessels by disrupting the angiogenesis-signaling cascade, and are used in the treatment of some malignancies and cancers.
What is the pathophysiology?
The pathophysiology of medication-related osteonecrosis of the jaw (MRONJ) is unknown, but several theories have been proposed. One theory suggests that inhibition of bone remodeling impairs the healing process, while another theory posits that inhibition of angiogenesis disrupts the blood supply, leading to avascular necrosis in the bone. Additionally, inflammation or infection from the mouth may cause bone necrosis, particularly affecting the jaw.
What is the incidence of MRONJ?
The incidence is up to 12 222 per 100 000 patient - years for bisphosphonates, and up to 2316 per 100 000 patient - years for denosumab. The incidence of medication - related osteonecrosis of the jaw in patients treated with anti-resorptive drugs for osteoporosis is significantly lower than oncology population. The incidence of MRONG in patients taking anti-resorptive drugs for osteoporosis may be ip to 150 per 100 000 patient years, which is only slightly higher than the general population. This means 150 people taking the medication for 1 year out of 100,000 will be diagnosed with MRONJ.
Below are some patients awho are at an increased risk:
● Cancer patients > Osteoporosis patient (cancer-related skeletal events requires higher dosages)
● Anatomic Factors – mandible and denture-wearing
● Oral surgery (e.g. Extraction)
● Pre-existing oral inflammatory disease (e.g. periodontal disease or periapical pathology)
● Immunocompromise (e.g. diabetes, corticosteroids, anaemia)
● Older age
● Longer duration, higher dosage, and higher potency of medication (IV > Oral)
What are the risk indications?
All patients at high risk of medication-related osteonecrosis of the jaw (MRONJ) should be referred to a specialist (oral surgeon or maxillofacial surgeon) for curettage and resection. Indications of high risk include:
● History of MRONJ/BRONJ
● Cancer management included antiresorptive or antiangiogenic medication
● Duration ≥4years of bisphosphonate therapy (cancer or non-cancer indication)
● Patient on Denosumab or bisphosphonates with additional risk factors (e.g. immune compromise, diabetes, corticosteroids, periodontal disease, dentures)
However, patients at low risk of MRONJ can be managed by a dentist with proper precautions. For the management of low-risk patients undergoing oral surgery, it is important to inform them of the MRONJ risk and to note that there is no evidence suggesting that a "drug holiday" reduces this risk. Antibiotic prophylaxis should not be used for low-risk patients. Dentists should ensure optimal oral hygiene, minimize trauma, and suture all mucoperiosteal flaps. Additionally, using chlorhexidine (CHX) mouth rinse and removing plaque both pre- and post-operatively are recommended, along with monitoring the patient until the wound heals. Non-healing wounds should not be debrided, and if bone remains visible after 8 weeks, the patient should be referred to a specialist.
What are the stages of MRONJ and relevant management?
Stage | Features | Management |
0 | Symptomatic (e.g. pain), radiographic changes, no exposed bone | Follow up and monitoring, systemic managment via antibiotics or analgesics |
1 | asymptomatic, exposed bone, no inflammation or infection | Follow up and monitoring, CHX mouth rinse, review indications of drugs |
2 | symptomatic (e.g. pain), exposed bone, adjacent soft tissue inflammation or secondary infection | CHX mouth rinse, oral antibiotics, analgestics, local debridement |
3 | symptomatic (e.g. pain), full thickness bone involvement, pathological fracture, extensive soft tissue infection and fistulae | CHX mouth rinse, roal antibiotics, analgesics, resection |
Note: - Removal of mobile, necrotic bone sequestrate always occurs regardless of stage
For patients taking despecific drugs, are there any precautions?
There is no evidence that drug holidays reduce the risk of medication - related osteonecrosis of the jaw. |
Denosumab is a reversible antireportive administrered every 6 months for soteoporosis. If it is possible to delaty a bone - invasive dental procedure in a patient taking denosumab for osteoporosis, ideally schedule the procedure just before the next dose of denosumab. It is never appropriate to interrupt or delay the dose, as withdrawal of denosumab has been associated with a an increased risk of spontaneous vertebral fractures.
For patients with cancer, the decision to alter antiresorptive therapy lies with the oncology team.
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