What is the overall risk of osteonecrosis of the jaw (ONJ) in patients on bisphosphonates?

Risk of Osteonecrosis of the Jaw (ONJ) with Bisphosphonate Therapy

The overall risk of ONJ in patients on bisphosphonates varies significantly by medication type and duration, with cumulative incidence ranging from 0.1% for oral bisphosphonates to up to 13% after 4 years of intravenous zoledronic acid treatment in cancer patients. 1

Risk Stratification by Medication Type and Patient Population

Intravenous Bisphosphonates (Higher Risk)

• Zoledronic acid: Highest risk among bisphosphonates

  • 10% cumulative incidence at 36 months (vs. 4% with pamidronate) 1
  • Relative risk of 9.5 compared to pamidronate alone 1
  • Cumulative hazard increases from 1% after 12 months to 11-13% at 4 years 1

• Multiple myeloma patients:

  • 7.4-11% incidence with intravenous bisphosphonates 1
  • 2.4% incidence reported in one study 2
  • 1% incidence in another study (attributed to less frequent use of zoledronic acid) 3

• Breast cancer patients:

  • 1.2% incidence with intravenous bisphosphonates 2
  • 2.9% incidence in breast cancer patients in another cohort 1

Oral Bisphosphonates (Lower Risk)

• Significantly lower risk: 0.1% prevalence (95% CI: 0.05% to 0.20%) 4
• Approximately 1 in 952 to 1 in 1,537 patients 4

Risk Factors for ONJ Development

Major Risk Factors

1. Bisphosphonate type:

   • Zoledronic acid carries highest risk 1, 5
   • Sequential therapy (pamidronate followed by zoledronic acid) has intermediate risk 1

2. Duration of exposure:

   • Risk increases with time: 1% at 12 months to 11-13% at 4 years 1
   • Higher cumulative doses significantly increase risk 2

3. Dental procedures:

   • Dental extractions increase risk dramatically (HR 53.19,95% CI: 18.20-155.46) 2
   • 60% of ONJ cases are preceded by dental surgical procedures 6

4. Underlying condition:

   • Cancer patients receiving IV bisphosphonates represent 94% of published cases 6
   • Patients with multiple myeloma and metastatic bone disease at highest risk 6
   • Osteoporosis is an independent risk factor (HR 6.11,95% CI: 1.56-23.98) 2

5. Anatomical site:

   • Mandible more commonly affected than maxilla (2:1 ratio) 6
   • Palatal tori can be sites of spontaneous ONJ 4

Additional Risk Factors

• Previous or concomitant chemotherapy, radiotherapy, corticosteroids 1
• Poor oral health 2
• Sequential therapy (prior BP therapy before switching to denosumab) 7

Prevention Strategies

• Pre-treatment dental evaluation: All cancer patients should receive comprehensive dental examination and preventive dentistry before starting bisphosphonate therapy 1

• Eliminate infection sources: All sites of potential jaw infection should be eliminated before initiating bisphosphonate therapy 6

• Ongoing dental care: Regular dental check-ups during treatment to monitor for oral infections and periodontal disease 8

• Avoid invasive dental procedures: When possible, especially in high-risk patients 1, 5

• Proper administration: For oral bisphosphonates, take on empty stomach with full glass of water, remain upright for 30 minutes 8, 9

Management of Established ONJ

• Conservative approach is preferred: débridement of necrotic bone, pain control, infection management, antimicrobial oral rinses 6

• Consider discontinuation of bisphosphonate therapy based on individual benefit/risk assessment 9, 5

• Resolution is possible but often prolonged: Only 23% of ONJ cases resolved with conservative therapy during median follow-up of 17.1 months 2

Important Caveats

• ONJ risk must be balanced against the benefits of bisphosphonate therapy in preventing skeletal-related events in cancer patients and fractures in osteoporosis

• For an 82-year-old female patient, consider her specific risk factors (dental health, planned procedures, comorbidities) when assessing individual ONJ risk

• The decision to stop bisphosphonates before dental procedures should be made collaboratively between the oral surgeon and primary care physician 8

• Patients should be informed about the risk of ONJ and instructed to report any oral symptoms promptly