When can bisphosphonates be safely restarted after a 5-year treatment period?

Restarting Bisphosphonates After 5 Years of Treatment

After completing 5 years of bisphosphonate therapy, treatment can be safely restarted based on an individualized fracture risk assessment, with most patients benefiting from a 2-3 year drug holiday before resumption of therapy if they remain at moderate-to-high fracture risk.

Factors Determining When to Restart Bisphosphonates

Fracture Risk Assessment

• Low-risk patients: May remain off bisphosphonates for up to 5 years after the initial 5-year treatment period 1
• Moderate-to-high risk patients: Should consider restarting after a 2-3 year drug holiday 1, 2

Risk Stratification Criteria

• High risk (requiring shorter drug holiday or immediate continuation):

  • T-score ≤ -2.5 at hip or spine
  • History of fragility fracture during or after therapy
  • New fracture while on drug holiday
  • Continuing glucocorticoid therapy ≥7.5mg prednisone daily 1
  • Significant BMD loss (≥10% per year) during the holiday period 1

• Moderate risk:

  • T-score between -2.0 and -2.5
  • FRAX score indicating elevated 10-year fracture risk
  • Multiple clinical risk factors

• Low risk:

  • T-score > -2.0
  • No history of fractures
  • No significant clinical risk factors

Monitoring During Drug Holiday

• Bone mineral density (BMD) testing every 1-2 years 1
• Bone turnover markers (if available)
• Clinical assessment for new fractures
• Reassess overall fracture risk annually

Special Considerations

Continuing Glucocorticoid Therapy

For patients who continue glucocorticoid treatment after a 5-year course of bisphosphonates, active treatment should be continued rather than implementing a drug holiday if they remain at moderate-to-high risk of fracture 1.

Type of Bisphosphonate

The duration of the drug holiday may vary based on the specific bisphosphonate used:

• Alendronate: 3-5 year holiday 3, 4
• Zoledronic acid: 3-6 year holiday 4
• Risedronate: 1-2 year holiday (shorter due to lower bone retention) 4

Breast Cancer Patients

For patients receiving bisphosphonates as part of breast cancer treatment, the standard recommendation is 3-5 years of treatment, with continuation only if fracture risk remains elevated 5.

Potential Risks of Long-Term Therapy

• Atypical femoral fractures: Rare but serious complication (3.0-9.8 cases per 100,000 patient-years) 5
• Osteonecrosis of the jaw: Very rare (<1 case per 100,000 person-years) 5
• Upper GI complications: More common with oral formulations 6

Algorithm for Restarting Therapy

1. After completing 5 years of initial therapy:

   • Perform BMD testing and fracture risk assessment
   • Review history of fractures during treatment

2. Decision pathway:

   • If high risk: Continue therapy or restart after 1-2 year holiday
   • If moderate risk: Implement 2-3 year drug holiday, then reassess
   • If low risk: Implement 3-5 year drug holiday, then reassess

3. During drug holiday:

   • Continue calcium and vitamin D supplementation
   • Monitor BMD every 1-2 years
   • Assess for new fractures

4. Indications for restarting therapy:

   • Significant BMD decline (≥10%)
   • New fracture
   • Increased fracture risk due to new medications (e.g., glucocorticoids)
   • End of recommended drug holiday period with persistent moderate-to-high risk

Conclusion

The decision to restart bisphosphonates after a 5-year treatment period should be based on a thorough assessment of fracture risk. For most patients, a drug holiday of 2-3 years is appropriate before restarting therapy, though this period may be shorter for high-risk patients and longer for those at lower risk. Regular monitoring during the drug holiday is essential to detect changes in fracture risk that would warrant resumption of therapy.