7.5 Impaired Healing: MRONJ, Osteoradionecrosis and Systemic Risk

6. Systemic Factors Impairing Bone Healing and Clinical Governance

Medication-Related Osteonecrosis of the Jaw (MRONJ)

MRONJ is a severe, debilitating adverse drug reaction characterized by progressive destruction and exposure of necrotic bone in the maxillofacial region.

• Diagnostic Consensus Criteria (SDCEP / AAOMS):
  1. Exposed necrotic bone, or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region, that has persisted for >8 weeks.
  2. Current or previous treatment with antiresorptive agents (bisphosphonates, RANKL inhibitors) or antiangiogenic agents.
  3. No history of radiation therapy to the jaw bones and no metastatic disease to the jaws.
• Pathophysiology:
  • Nitrogen-containing bisphosphonates (e.g., zoledronic acid, pamidronate, alendronate) bind tenaciously to exposed hydroxyapatite crystals. During bone resorption, osteoclasts internalize the drug, which potently inhibits farnesyl pyrophosphate (FPP) synthase in the mevalonate pathway. This blocks protein prenylation of small GTPases (Ras, Rho, Rac), inducing osteoclast cytoskeletal collapse, loss of the ruffled border, and apoptosis.
  • Alveolar bone, possessing a high natural turnover rate, absorbs large drug concentrations. Surgical dental extractions or mucosal microtrauma cannot undergo physiological remodelling; the exposed bone becomes necrotic, colonized by oral biofilms (Actinomyces species), and fails to heal.
• Risk Stratification & UK SDCEP Guidance:
  • High Risk: Patients receiving intravenous antiresorptives or subcutaneous denosumab for oncology (malignancy/bone metastases); cumulative MRONJ risk post-extraction is 1% to 15%.
  • Low Risk: Patients receiving oral or subcutaneous antiresorptives for osteoporosis or non-malignant bone disease for <5 years (without systemic glucocorticoids); absolute MRONJ risk is negligible (~0.01% to 0.1%).
  • Clinical Management: Traumatic extractions must be avoided. Treatment includes atraumatic surgical technique, complete bone edge smoothing, primary tension-free mucosal closure, and follow-up at 8 weeks to confirm mucosal healing. Routine prophylactic systemic antibiotics are not indicated for low-risk patients under UK SDCEP guidance.

Osteoradionecrosis (ORN)

• Severe necrotic non-healing bone complication following radiotherapy for head and neck squamous cell carcinoma exceeding therapeutic doses of >50 to 60 Gy.
• Pathophysiology (Marx's Classical Triad): Radiation induces permanent microvascular damage characterized by endarteritis obliterans, endothelial cell death, and peri-arteriolar fibrosis, resulting in tissue that is profoundly: Hypovascular + Hypocellular + Hypoxic Delaval's radiation-induced fibroatrophy theory underscores that irradiated bone loses all capacity for normal BMU remodeling and physiological repair following extraction trauma.
• Clinical Prevention: Pre-radiation dental screening is mandatory. Unrestorable teeth or teeth with questionable prognosis must be extracted at least 14 to 21 days prior to the commencement of radiotherapy to ensure primary epithelial and initial osseous healing.

Diabetes Mellitus

• Chronic hyperglycaemia results in non-enzymatic glycation of circulating proteins, forming Advanced Glycation End-products (AGEs).
• AGEs bind to their cell-surface receptor RAGE on macrophages, endothelial cells, and osteoblasts, generating persistent intracellular reactive oxygen species (ROS) and sustaining continuous transcription of TNF-α and IL-1β.
• This locks wound macrophages into an unresolving pro-inflammatory M1 phenotype, impairing the transition to reparative M2 macrophages. Osteoblast apoptosis is accelerated, collagen synthesis is suppressed, angiogenesis is defective, and neutrophil chemotaxis and phagocytosis are blunted.
• Result: Markedly delayed socket epithelialization, delayed woven bone formation, and elevated risk of postoperative wound infection and dry socket (alveolar osteitis). Elective dentoalveolar surgery requires optimized glycaemic control (target HbA1c < 7.0% / 53 mmol/mol).

Tobacco Smoking

• Pharmacological Vasoconstriction: Nicotine rapidly triggers systemic release of catecholamines (adrenaline and noradrenaline), causing profound peripheral capillary vasoconstriction and reducing mucosal and alveolar microcirculation.
• Tissue Hypoxia: Carbon monoxide competitively binds haemoglobin, forming carboxyhaemoglobin and shifting the oxygen-haemoglobin dissociation curve to the left, inducing deep tissue hypoxia.
• Cellular Toxicity: Nicotine directly suppresses osteoblast alkaline phosphatase activity, blocks Type I collagen secretion, impairs fibroblast adhesion, and suppresses neutrophil oxidative burst.
• Alveolar Osteitis (Dry Socket): The physical negative intraoral pressure generated during cigarette inhalation, combined with microvascular ischemia and localized fibrinolysis, frequently dislodges the immature blood coagulum. The incidence of dry socket in smokers is 3 to 4 times higher than in non-smokers (~12–15% vs ~2–3%).

Worked Clinical SBA Scenario

Scenario: A 66-year-old female presents with severe pain and food stagnation associated with a non-restorable, fractured mandibular left first permanent molar (LL6 / 36). Her medical history reveals that she has been taking oral alendronic acid (70 mg once weekly) for 3 years to manage postmenopausal osteoporosis. She is not taking systemic corticosteroids. Periapical radiography shows extensive coronal and radicular caries with a localized apical radiolucency. The alveolar lamina dura is intact around adjacent teeth.

Question: Under UK SDCEP guidelines, what is this patient's MRONJ risk category, and what is the appropriate clinical extraction protocol?

Analysis and Clinical Governance: Under the Scottish Dental Clinical Effectiveness Programme (SDCEP) guidelines, a patient receiving oral bisphosphonates for osteoporosis for less than 5 years without concurrent systemic corticosteroids is classified as low risk for MRONJ (estimated incidence of ~1 in 1,000 to 1 in 10,000 extractions). Treatment should proceed in primary dental care:

1. Inform the patient of the very low risk of MRONJ and document informed consent.
2. Perform an atraumatic extraction avoiding unnecessary mucoperiosteal flap reflection or extensive bone removal.
3. Remove any sharp bony socket margins, achieve haemostasis with local pressure, and advise the patient on gentle post-extraction care.
4. Routine prophylactic systemic antibiotics are not recommended.
5. Schedule a review appointment at 8 weeks post-extraction to confirm complete mucosal coverage of the socket bed. If unhealed, exposed bone persists at 8 weeks, prompt referral to an oral and maxillofacial surgery specialist unit is indicated.