When to discontinue alendronate (bisphosphonate) in patients?

When to Discontinue Alendronate (Bisphosphonate) in Patients

Alendronate should be discontinued after 5 years of treatment in most patients, with consideration for continuation only in those at very high fracture risk. 1

Decision Algorithm for Alendronate Discontinuation

Patients Who Should Discontinue After 5 Years:

• Patients with moderate fracture risk
• Patients who have achieved good BMD response (T-score > -2.5)
• Patients without recent fractures

Patients Who Should Continue Beyond 5 Years:

• Patients at very high risk of fracture:
  • T-score ≤ -3.5
  • History of osteoporotic fracture while on treatment
  • High-dose glucocorticoid use 2
  • Patients with multiple myeloma with bone metastases 3
  • Patients with cancer and bone metastases 3

Evidence Supporting Discontinuation

Research shows that after 5 years of alendronate treatment, discontinuation does not significantly increase fracture risk compared to continued treatment. A population-based cohort study found no difference in fracture rates between patients who discontinued versus those who continued alendronate after 5 years of treatment 1. This suggests that the drug's protective effects persist after discontinuation.

The persistence of alendronate's effects is due to its long half-life in bone (>10 years) 4. When treatment is stopped after 5 years, BMD decreases slowly (approximately 1.5% in the spine and <3% in the femur over 5 years), but remains higher than pre-treatment levels 5, 4.

Monitoring After Discontinuation

After discontinuing alendronate:

• Monitor BMD every 1-2 years
• Assess for new fractures
• Evaluate for changes in risk factors
• Consider restarting treatment if:
  • Significant BMD decline (>5%)
  • New fracture occurs
  • Risk factors for fracture significantly worsen

Special Considerations

Cancer Patients

For patients with cancer and bone metastases, bisphosphonate therapy should be continued throughout the course of the disease 3. In multiple myeloma, bisphosphonates should be initiated at diagnosis and can be interrupted after 2 years in patients in remission 3.

Adverse Effects Requiring Discontinuation

Discontinue alendronate immediately if patients develop:

• Dysphagia, odynophagia, or retrosternal pain
• New or worsening heartburn
• Atypical femoral fractures (consider discontinuation based on risk/benefit assessment) 6
• Osteonecrosis of the jaw (consider discontinuation based on risk/benefit assessment) 6

Renal Impairment

Alendronate is not recommended for patients with creatinine clearance less than 35 mL/min 6. If discontinued due to renal dysfunction, do not restart until renal function returns to baseline 2.

Drug Holiday Considerations

The concept of a "drug holiday" after 5 years of treatment is supported by evidence showing that alendronate's effects persist after discontinuation 5, 4. This approach may help reduce the risk of rare but serious adverse effects associated with long-term use, such as atypical femoral fractures and osteonecrosis of the jaw, while maintaining fracture protection.

Resuming Treatment

If alendronate is restarted after a drug holiday, patients should follow proper administration guidelines:

• Take on an empty stomach with a full glass (6-8 oz) of plain water
• Remain upright for at least 30 minutes after taking
• Avoid food, beverages, and other medications for at least 30 minutes after taking 2, 6

For patients who cannot tolerate oral bisphosphonates after restarting, consider alternative treatments such as intravenous bisphosphonates or other medication classes 2.