A quick MRONJ refresh for new graduates

As new graduates embark on their early dental careers, it's essential for them to be prepared for conditions like medication-related osteonecrosis of the jaw (MRONJ), which can have significant implications if not managed appropriately. Antiresorptive and antiangiogenic therapies are used to manage common medical conditions, so staying informed about MRONJ helps manage patients safely. I’ve provided a quick refresh on the essential information required to safely manage patients at risk of MRONJ. 

What is MRONJ? 

Medication-related osteonecrosis of the jaw (MRONJ) involves the incidence of exposed bone within the maxillofacial region that has not healed within eight weeks in patients with a history of antiresorptive or antiangiogenic drug therapy, and no history of radiation therapy to the jaw (Aldhalaan et al., 2020). The term MRONJ replaced bisphosphonate-related osteonecrosis of the jaw (BRONJ) to include a wider range of medications beyond bisphosphonates. 

Who is at risk of MRONJ? 

Patients undergoing treatments that influence bone metabolism. These medications include: 

• Bisphosphonates (e.g., alendronate, zoledronic acid) – Prescribed for osteoporosis, Paget’s disease, and metastatic bone disease. 

• RANKL inhibitors (e.g., denosumab) – Used for osteoporosis and cancer-related bone loss. 

• Antiangiogenic agents (e.g., bevacizumab, sunitinib) – Employed in cancer therapy to inhibit tumor blood supply. 

Risk factors can be categorized into drug-related, local, and systemic factors: 

• Drug-related: Higher doses, intravenous administration, and prolonged usage increase risk. Recent studies have highlighted that combining antiresorptive and antiangiogenic therapies can elevate the risk of developing MRONJ compared to single-drug regimens (Srivastava et al., 2021).

• Local factors: Dental procedures like tooth extractions, implants, or trauma to the oral mucosa can precipitate MRONJ. Yes, that means even something as simple as an ill-fitting denture.

• Systemic factors: Conditions such as cancer, steroid use, diabetes, and smoking further predispose patients. Systematic reviews indicate that MRONJ is more common in females than males, with the mandible being the most frequently affected site (Frutuoso et al., 2024). 

Clinical risk assessment and diagnosis 

MRONJ is staged based on severity, guiding management strategies: 

• Stage 0: No clinical evidence of necrotic bone but presents with non-specific symptoms (e.g., jaw pain, sinus tract formation). 

• Stage 1: Exposed necrotic bone without signs of infection or inflammation. 

• Stage 2: Exposed necrotic bone accompanied by pain, infection, and erythema. 

• Stage 3: Extensive necrosis with pathological fractures, extraoral fistula, or osteolysis extending beyond the alveolar bone. 

Don’t forget education and informed consent. When treating patients on medications like denosumab (Prolia) or other antiresorptive drugs, it's imperative to discuss MRONJ risks before performing invasive dental procedures. The informed consent process should clarify that: 

• There is a continued need for updated, comprehensive medical history taking at each appointment, with consideration of additional medications that may elevate MRONJ risk, such as systemic glucocorticoids. 

• The patient may need to consider other treatment options for dental infections, including endodontic therapy, as an alternative to extraction if achievable. 

• That tooth extractions significantly increase MRONJ risk, emphasizing alternative, lower-risk treatments when applicable. 

• That MRONJ means dead bone due to compromised healing after invasive procedures and that the medications (such as Prolia) are responsible for that delayed healing, increasing the risk of osteonecrosis. 

• A drug holiday isn’t usually advocated, primarily due to the benefits of continued drug therapy outweighing the minor risk for MRONJ development. 

• There is a potential need for oral surgeon referral for complex extractions or high-risk cases. 

• That primary prevention, encouraging collaboration with the patient's GP and diligent follow-up post-extraction to detect complications early. 

Prevention is the primary focus 

Prevention is paramount to moderate MRONJ risk: 

1. Identify at-risk patients: Conduct thorough medical histories, specifically asking about bisphosphonates and antiresorptive therapies. 
2. Dental clearance before therapy: Ensure necessary extractions, periodontal therapy, or other invasive procedures are completed before starting these medications. Other considerations can include inspecting any oral devices or prosthesis that the patient is using and ensuring they are not causing trauma to the oral mucosa.
3. Minimize surgical trauma: Atraumatic techniques should be used during extractions. Aim for primary closure and consider antibiotic prophylaxis when appropriate.
4. Educate patients: Advise at-risk patients on maintaining excellent oral hygiene, scheduling routine dental checkups, and promptly reporting any jaw pain or non-healing wounds. 

A systematic review and meta-analysis by Srivastava et al. in 2021 highlights that the variations in MRONJ prevalence were the result of oral examinations carried out prior to initiating drug therapy; meaning that preventative treatment with strict protocols resulted in lower MRONJ prevalence.

Managing MRONJ within the practice  

Management of MRONJ varies by stage: 

• Stage 0 & 1: Conservative measures such as regular dental recalls, regular oral hygiene instruction and modification, topical antiseptics (e.g., chlorhexidine), and regular monitoring and inspection of dental prostheses. Chlorhexidine 0.12% is a frequently used mouth rinse reported in recent systematic reviews.

• Stage 2: Administration of systemic antibiotics (e.g., penicillin or clindamycin for allergic patients) along with pain management. The most used antibiotics for treatment are amoxicillin with clavulanic acid (875 mg + 125 mg) administered orally twice a day, for 5 days.

• Stage 3: Surgical debridement or resection may be necessary, often requiring referral to an oral surgeon. Surgical debridement is the most reported approach for more severe cases (Frutuoso et al., 2024). 

Understanding MRONJ is vital for delivering optimal patient care. Recognizing at-risk individuals and emphasizing prevention are two of the most important aspects to withdraw from this article. As always, keep up to date with your knowledge through research articles and CPD. Don’t forget to communicate with an oral surgeon and the patient’s GP.

Additional references

AlDhalaan, N. A., BaQais, A., & Al-Omar, A. (2020). Medication-related Osteonecrosis of the Jaw: A Review. Cureus, 12(2), e6944. https://doi.org/10.7759/cureus.6944