How many years should a woman remain off alendronate (bisphosphonate) after being on it for five years?

Duration of Alendronate Holiday After Five Years of Treatment

After completing five years of alendronate therapy, women should remain off the medication for up to five years, as data from the FLEX study suggests continued fracture protection during this period. 1

Evidence-Based Rationale for Drug Holiday

The recommendation for a five-year drug holiday after five years of alendronate therapy is supported by multiple high-quality guidelines:

• The American Geriatrics Society notes that women who have taken alendronate for five years can stop the medication and still have fracture protection for up to five more years 1
• The American College of Physicians (ACP) recommends treating osteoporotic women with pharmacologic therapy for 5 years, with consideration of stopping bisphosphonate treatment after this period 1
• Current evidence suggests that increasing bisphosphonate therapy beyond 5 years probably reduces risk for new vertebral fractures but not other fractures, while increasing risk for long-term harms 1

Factors Influencing Duration of Drug Holiday

The decision regarding the length of the drug holiday should be based on:

1. Baseline Fracture Risk: Women with higher baseline fracture risk may benefit from shorter drug holidays
2. Bone Mineral Density (BMD) at Discontinuation: The FLEX study demonstrated that women with femoral neck T-scores ≤ -2.5 after 5 years of alendronate had greater fracture risk after discontinuation 2, 3
3. Age: Older age at the time of discontinuation is significantly related to increased fracture risk 2

Monitoring During Drug Holiday

• BMD monitoring during the initial 5-year treatment period is not recommended 1
• Follow-up measurements of DXA 1 year after discontinuation and bone turnover markers 1-2 years after discontinuation are not associated with fracture risk and cannot be recommended 2
• Regular reassessment of fracture risk is essential during the drug holiday period 4

When to Consider Resuming Treatment

Consider resuming bisphosphonate therapy before completing the full 5-year holiday if:

• Significant bone loss occurs (>5% at hip)
• New fracture occurs during the holiday period
• The patient's T-score falls below -2.5 at the femoral neck 3

Risks of Long-Term Alendronate Use

Extending alendronate therapy beyond 5 years increases the risk of rare but serious adverse events:

• Osteonecrosis of the jaw: less than 1 case per 100,000 person-years 4
• Atypical femoral fractures: 3.0-9.8 cases per 100,000 patient-years 4

Benefits of the Drug Holiday Approach

1. Reduces risk of rare but serious adverse events associated with long-term bisphosphonate use
2. Maintains fracture protection due to alendronate's persistence in bone tissue
3. After discontinuation, BMD remains higher and reduction in bone turnover remains greater than pre-treatment values 5

Common Pitfalls to Avoid

• Pitfall: Monitoring BMD during the first year of drug holiday to guide decisions

  • Avoid by: Recognizing that 1-year changes in hip DXA after discontinuation are not predictive of subsequent fracture risk 2

• Pitfall: Continuing alendronate indefinitely without consideration of drug holiday

  • Avoid by: Implementing a structured approach to evaluate the need for continued therapy after 5 years

• Pitfall: Failing to identify patients who may benefit from continued therapy

  • Avoid by: Recognizing that women with femoral neck T-scores ≤ -2.5 after 5 years of therapy may benefit from continued treatment 3

In conclusion, the optimal approach is to provide a 5-year drug holiday after 5 years of alendronate therapy, with consideration for earlier resumption of treatment based on individual fracture risk factors.