Mandibular molar extraction in a patient on high-dose denosumab

Risk category: high. The drivers are:

• Drug and indication – denosumab at the oncology dose (120 mg monthly) for bone metastases carries the highest risk of any antiresorptive regimen; lower-dose osteoporosis therapy carries far less risk.
• Duration – 26 months of continuous therapy. Risk rises with time and with cumulative exposure.
• Modifiable co-factors – HbA1c 7.8% and 10 cigarettes/day both impair mucosal healing and add independent risk.
• Local factors – chronic periapical infection with a sinus tract, which cannot be left indefinitely.

She does not have MRONJ today. There is no exposed bone, so this is a high-risk patient needing a dentoalveolar procedure, not a staged osteonecrosis. Treating it as MRONJ and refusing surgery would leave an infected tooth as an ongoing inflammatory stimulus, which is itself a recognised trigger.

Decision: proceed, but proceed well. Extraction is reasonable in a primary oral surgery setting because the tooth is a single-rooted-format molar with accessible anatomy, no acute spreading infection and no need for extensive bone removal. What matters is technique: adequate anaesthesia, atraumatic elevation, sectioning rather than force, minimal periosteal stripping, smoothing of sharp bone edges, primary soft-tissue closure and haemostasis. Many clinicians add a 0.12% chlorhexidine rinse starting the day before and continuing for 2 weeks, and some give a short perioperative antibiotic course, although the evidence for the latter is weak. Referral to a hospital OMFS unit is reserved for teeth requiring significant bone removal, multi-rooted teeth with divergent roots, or where primary closure cannot be achieved.

What the pharmacology tells us. Denosumab is a fully human monoclonal antibody against RANKL with a half-life of roughly 26–28 days. Unlike bisphosphonates, it is not incorporated into bone, so its effect on bone turnover reverses within about 6–9 months of the last dose. That cuts both ways: any theoretical benefit of interrupting therapy disappears quickly, and so does protection against skeletal-related events (pathological fracture, spinal cord compression, hypercalcaemia).

What the evidence tells us. There is no high-quality evidence that a drug holiday before oral surgery reduces the incidence of MRONJ. Guidance bodies are cautious: an interruption may be considered in selected patients after discussion with the treating physician, but it is not a routine requirement, and it is least attractive in patients on high-dose therapy for malignancy, where the oncological stakes are highest. Serum CTX is not validated for denosumab and should not be used to justify a delay.

What I would say to her. "Stopping the injection has not been shown to make this safer, and your cancer treatment matters. I do not want to delay removing an infected tooth to gain a benefit we cannot demonstrate. I will write to your oncologist so the decision is shared and documented, but I would plan to go ahead."

Who decides. The decision to interrupt antiresorptive therapy belongs to the prescribing oncologist. Your role is to communicate the dental plan, the urgency, the local risk factors and the lack of evidence for a holiday - then operate on agreed timing.

Consent should cover:

• The diagnosis and why the tooth cannot be retained.
• The quantified risk of MRONJ - quote a range for high-dose antiresorptive patients (commonly several percent), and say clearly that the risk is not zero and is not abolished by any drug holiday.
• Alternatives: root canal treatment plus restoration (possible but the tooth is heavily broken down and the long-term prognosis is guarded), long-term antibiotics (suppresses but does not resolve), or doing nothing (progression of infection).
• The possibility of further surgery, sequestration or, rarely, resection if osteonecrosis develops.
• Post-operative instructions, chlorhexidine use, and the need to report non-healing immediately.

Review plan: telephone or clinical review at 1 week (soft tissue healing, pain, no bone visible), 4 weeks, and 8 weeks; then 6-monthly for at least a year, since MRONJ can present late. Photograph and document any mucosal defect.

At 8 weeks with 5 mm of exposed bone: this now meets the case definition of MRONJ (exposed bone persisting beyond 8 weeks in a patient on antiresorptive therapy).

1. Stage it. If there is no pain, erythema or purulence, it is Stage 1 - manage conservatively: continue 0.12% chlorhexidine, gentle debridement of the socket, avoid trauma, review 8-weekly, do not perform aggressive resection.
2. If there is infection (purulence, erythema, pain) it is Stage 2 - add systemic antibiotics (amoxicillin with metronidazole, or clindamycin if penicillin-allergic), superficial debridement and analgesia.
3. Reserve Stage 3/4 measures (segmental resection, reconstruction) for extensive disease, and refer to a specialist unit if it progresses.

Document the staging, inform the oncologist, and record the timeline carefully.