Drug Holiday Duration After 5 Years of Alendronate Therapy
For patients at low-to-moderate fracture risk after 5 years of alendronate, a drug holiday of 3-5 years is satisfactory, while high-risk patients should take a shorter holiday of 1-2 years with close monitoring. 1, 2, 3
Risk Stratification Determines Holiday Length
The duration of your drug holiday depends entirely on fracture risk after completing 5 years of therapy:
Low-to-Moderate Risk Patients (3-5 Year Holiday)
- No previous hip or vertebral fractures during treatment 4
- Hip BMD T-score > -2.5 after treatment 4
- No ongoing high-dose glucocorticoid use 4
- Age <80 years 4
For these patients, alendronate specifically allows a 3-5 year drug holiday due to its long skeletal retention time 3. The FLEX trial demonstrated that women who discontinued alendronate after 5 years had only a modest increase in clinical vertebral fractures (5.3% vs 2.4%) but no difference in non-vertebral or hip fractures over the subsequent 5 years 4.
High-Risk Patients (1-2 Year Holiday Maximum)
- Previous hip or vertebral fractures 4, 2
- Hip BMD T-score ≤ -2.5 despite treatment 4, 3
- Age >80 years 4
- Ongoing glucocorticoid therapy ≥7.5 mg prednisone daily 4
- Multiple non-spine fractures 4
These patients should have a maximum 1-2 year drug holiday with close monitoring 1, 2. Evidence shows that resurgent bone turnover becomes problematic in high-risk patients, with fractures recurring as early as 12 months following discontinuation 5.
Critical Timing Considerations
Do not extend drug holidays beyond 2 years without reassessment, as fracture risk increases significantly after this threshold 6. A large Medicare study of 81,427 women found that discontinuing alendronate for >2 years increased hip fracture risk (HR 1.3,95% CI 1.1-1.4), humerus fracture risk (HR 1.3,95% CI 1.1-1.66), and clinical vertebral fracture risk (HR 1.2,95% CI 1.1-1.4) compared to continuing therapy 6.
Monitoring During the Holiday
Perform BMD with vertebral fracture assessment every 1-2 years during the drug holiday 2. Resume treatment immediately if:
Agent-Specific Differences Matter
Alendronate provides the most durable protection during drug holidays compared to risedronate 5, 7. A 2024 Australian study found that postfracture mortality was higher in patients who discontinued risedronate for 1 year (HR 2.37) or 2 years (HR 3.08), but no increase was observed with alendronate discontinuation 7. This reflects alendronate's longer skeletal retention and more sustained antiresorptive effect 5, 8.
Common Pitfalls to Avoid
Never discontinue therapy without first performing comprehensive fracture risk reassessment including updated FRAX score, BMD measurement, and vertebral fracture assessment 2. Five years of alendronate was insufficient in preventing vertebral fractures in high-risk patients embarking on a drug holiday 5.
Do not apply the same holiday duration to all bisphosphonates—risedronate requires shorter holidays (1-2 years) due to relatively faster offset of antiresorptive effect, while alendronate allows 3-5 years 3. Zoledronic acid confers the most durable reduction (3-6 years possible) particularly after six annual infusions 5, 3.