What are the guidelines for a drug holiday with bisphosphonates (bone resorption inhibitors)?

Bisphosphonate Drug Holiday Guidelines

After 5 years of bisphosphonate therapy, clinicians should consider stopping treatment (drug holiday) unless the patient has a strong indication for treatment continuation. 1

Risk Stratification for Drug Holiday Decision

The decision to implement a bisphosphonate drug holiday should be based on fracture risk assessment:

Low to Moderate Risk Patients (Consider Drug Holiday)

• T-score > -2.5
• No recent fragility fractures
• Stable BMD on treatment
• Completed 5 years of oral bisphosphonates or 3 years of IV zoledronic acid

High Risk Patients (Continue Treatment)

• T-score ≤ -2.5, especially at hip
• Recent fragility fractures
• Multiple risk factors for fracture
• History of vertebral fractures
• On long-term glucocorticoid therapy

Duration of Drug Holiday

The duration varies based on the specific bisphosphonate used due to differences in bone retention:

• Alendronate: 3-5 year holiday after 5 years of treatment 1, 2
• Risedronate: 1-2 year holiday after 5 years of treatment (shorter due to faster offset of effect) 2, 3
• Zoledronic acid: 3-6 year holiday after 3 years of treatment 2, 3

Monitoring During Drug Holiday

Regular monitoring is essential during the drug holiday period:

• BMD testing every 1-2 years 2
• Bone turnover markers (if available) to detect resurgent bone turnover 4
• Clinical assessment for new fractures
• Reassessment of FRAX score annually 2

When to Resume Treatment

Treatment should be resumed if any of the following occur during the drug holiday:

• Significant BMD decline (>5% at hip or spine)
• Bone turnover markers increase significantly above pre-treatment levels
• New fracture occurs
• FRAX score increases to ≥20% for major osteoporotic fracture or ≥3% for hip fracture 2

Special Considerations

Denosumab

Unlike bisphosphonates, denosumab should not be discontinued without follow-up therapy due to risk of rebound bone loss and multiple vertebral fractures 2, 3

High-Risk Patients

For patients at very high fracture risk, consider:

• Longer treatment duration (up to 10 years) 2, 5
• Shorter drug holidays (1-2 years) 5
• Alternative therapy during the holiday period (e.g., raloxifene) 6

Risks of Long-Term Bisphosphonate Use

• Atypical femoral fractures: Risk increases with duration of use beyond 5 years 1, 4
• Osteonecrosis of jaw: Risk increases with longer treatment duration 1

Fracture Risk During Drug Holiday

Studies show that fracture risk during bisphosphonate drug holidays:

• Remains relatively low in the first 1-3 years 4
• Increases in years 4-5 of the holiday (9.8-9.9% annual fracture incidence) 7
• Is higher in patients with lower femoral neck BMD at baseline 7

Practical Recommendations

1. Complete initial 5-year course of bisphosphonate therapy
2. Assess fracture risk using BMD, fracture history, and FRAX
3. Implement drug holiday in appropriate patients
4. Monitor regularly during holiday period
5. Resume treatment promptly if fracture risk increases

Remember that the primary goal is to balance the benefits of fracture prevention against the risks of rare but serious adverse events from prolonged bisphosphonate use.