What are the guidelines for an Alendronate (bisphosphonate) holiday in patients on long-term therapy?

Alendronate Holiday Guidelines for Long-Term Therapy

Patients on long-term alendronate therapy should be considered for a drug holiday after 3-5 years of treatment, with the decision based primarily on fracture risk assessment. 1, 2

Risk Assessment for Drug Holiday Decisions

High-Risk Patients (Continue Therapy)

• T-score ≤ -2.5 at hip
• Previous major osteoporotic fracture
• Fracture while on therapy
• Older age with multiple risk factors

Moderate to Low-Risk Patients (Consider Drug Holiday)

• T-score > -2.5
• No history of fractures
• Younger patients with fewer risk factors

Duration of Drug Holiday

• Alendronate: 2-3 year holiday after 5 years of treatment 2, 3
• Monitoring during holiday: Reassess BMD after 1-2 years 1
• Resume therapy if:
  • New fracture occurs
  • Significant BMD decline (>5% at hip)
  • T-score falls to ≤ -2.5
  • Increase in fracture risk factors 1

Evidence Supporting Drug Holidays

The concept of bisphosphonate holidays emerged from concerns about rare but serious adverse events associated with long-term use, including:

• Atypical femoral fractures (AFF)
• Osteonecrosis of the jaw (ONJ) 4, 2

The American Society for Bone and Mineral Research Task Force suggests that after 5 years of oral bisphosphonate therapy, risk reassessment should be conducted 2. This recommendation is based on evidence from key trials:

• FLEX trial: Women receiving alendronate for 10 years had fewer clinical vertebral fractures than those switched to placebo after 5 years 2
• HORIZON extension: Continued benefit for vertebral fracture reduction with extended therapy 2

Rationale for Drug Holidays

1. Persistent effect: Bisphosphonates incorporate into bone matrix and continue to provide anti-resorptive effects after discontinuation 4
2. Risk reduction: May allow normal bone turnover to resume, potentially reducing risk of adverse events 4
3. Benefit-risk balance: For low-risk patients, the benefits of continued therapy may not outweigh potential risks 2

Monitoring During and After Drug Holiday

• BMD testing every 1-2 years
• Bone turnover markers may be useful for monitoring response
• Regular fracture risk assessment using validated tools 1

Special Considerations

• Cancer patients with bone metastases: Should continue bisphosphonate therapy throughout the course of disease 1
• Glucocorticoid-induced osteoporosis: Similar approach may be applicable with some adaptations 2
• Dental procedures: Low-risk dental procedures do not require discontinuation of alendronate, while moderate to high-risk procedures may require temporary discontinuation 1

Important Caveats

• The FDA label notes: "The optimal duration of use has not been determined. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis." 5
• Drug holidays are not appropriate for denosumab due to risk of rebound fractures upon discontinuation 3
• Most evidence for drug holidays comes from studies in postmenopausal women and may not be directly applicable to all populations 2

Remember that the decision to initiate a drug holiday should be based on a thorough assessment of individual fracture risk, and patients should continue calcium (1,000-1,200 mg/day) and vitamin D (600-800 IU/day) supplementation during the holiday period 1.