Makindo Medical Notes

Related Subjects: | Bisphosphonates | Osteoporosis | Osteonecrosis of the jaw

⚠️ Osteonecrosis of the Jaw (ONJ) is a rare but serious complication of drugs that inhibit bone resorption, notably bisphosphonates and denosumab. 🦷 It involves avascular necrosis of jawbone due to impaired osteoclastic activity and microvascular compromise, leading to exposed, non-healing bone and risk of secondary infection.

🧠 About

• First recognised in 2002 in patients receiving high-dose intravenous bisphosphonates for cancer-related bone disease.
• Occurs due to suppression of normal bone turnover and impaired healing after trauma or dental procedures.
• Incidence: up to 1–10% in oncology patients on IV bisphosphonates or denosumab, and <0.1% in osteoporosis treatment.
• Typically affects the mandible > maxilla (2:1 ratio), reflecting differences in vascularity.

⚙️ Pathophysiology

• Normal bone remodelling relies on osteoclast-mediated resorption and subsequent new bone formation.
• Bisphosphonates and denosumab inhibit osteoclasts → reduced bone turnover → accumulation of microdamage.
• Reduced angiogenesis and microcirculatory changes impair bone repair capacity.
• Local trauma, infection, or dental extraction then triggers exposure and necrosis of bone.

🧬 Aetiology

• Dental or surgical trauma (tooth extraction, implants, poorly fitting dentures).
• Suppression of osteoclasts by bisphosphonates or RANKL inhibitors (denosumab).
• Chemotherapy, corticosteroids, and poor oral hygiene further increase risk.
• Cancer patients, particularly with multiple myeloma or metastatic breast/prostate cancer, are at highest risk.

💊 Causes

• 💉 Drugs: Denosumab (RANKL inhibitors), IV or oral bisphosphonates, corticosteroids, antiangiogenic agents (bevacizumab, sunitinib).
• 🏥 Cancer-related: metastatic bone disease, myeloma, head and neck radiotherapy.
• 🦠 Infection or trauma: tooth extraction, ill-fitting dentures, periodontal disease.

🦷 Clinical Features

• Exposed bone: hallmark sign — non-healing exposed bone in oral cavity persisting >8 weeks.
• Pain and swelling: due to secondary infection or exposed bone edges.
• Loose teeth: teeth in affected region may become mobile.
• Numbness or heaviness: due to inferior alveolar nerve involvement.
• Pus or discharge: may indicate secondary osteomyelitis.

🔍 Investigations

• Clinical examination: exposed necrotic bone, mucosal ulceration, purulent discharge.
• Imaging: OPG, CT or MRI to assess bony involvement and sequestra.
• Microbiology: swabs/cultures if infection suspected.
• Blood tests: renal function, calcium, vitamin D, inflammatory markers.
• Medication and dental history: crucial to identify bisphosphonate or denosumab exposure.

🧩 Differential Diagnosis

• Osteomyelitis of the jaw.
• Metastatic bone disease.
• Chronic periodontitis.
• Post-radiation osteonecrosis (distinct pathogenesis).

🦷 Prevention

• Comprehensive dental assessment before starting bisphosphonates or denosumab.
• Complete any required dental extractions or invasive work prior to therapy.
• Maintain excellent oral hygiene and schedule regular dental check-ups.
• Inform dentists about antiresorptive therapy before any procedure.
• Avoid elective dental extractions or implants during therapy where possible.
• Encourage smoking cessation and good nutrition to promote mucosal healing.

🩺 Management

• Conservative (early stage): Chlorhexidine mouth rinses, analgesia, antibiotics if secondary infection, and avoidance of further dental trauma.
• Medical: Consider temporary interruption of antiresorptive therapy (in consultation with specialist). Correct calcium and vitamin D deficiency.
• Surgical (advanced cases): Surgical debridement or resection of necrotic bone; reconstructive surgery if extensive involvement.
• Multidisciplinary care: Coordinate between dentist, maxillofacial surgeon, oncologist/endocrinologist.

⚠️ Key Risks and Monitoring

• Higher risk with IV bisphosphonates and high-dose denosumab (120 mg monthly for cancer).
• Lower risk with oral bisphosphonates and osteoporosis-dose denosumab (60 mg 6-monthly).
• Monitor for jaw pain, loose teeth, or non-healing ulcers.
• Reinforce patient education — early reporting prevents progression.

💡 Teaching Tip

• Explain to students that ONJ represents the “double hit” of impaired bone turnover and reduced vascularity.
• Compare with osteoradionecrosis — both cause devitalised bone, but via different mechanisms (radiation vs osteoclast suppression).
• Mnemonic: “BRONJ” = Bisphosphonate-Related OsteoNecrosis of the Jaw, though denosumab now adds “DRONJ”.

📚 References

• BNF: Denosumab and Bisphosphonates
• MHRA Drug Safety Update (2015): Osteonecrosis of the jaw with antiresorptive agents
• Ruggiero SL et al. J Oral Maxillofac Surg 2014;72(10):1938–1956 — AAOMS Position Paper on ONJ.
• NICE CKS: Osteoporosis, Bone Health (2024).