Bisphosphonate Drug Holiday Guidelines
Duration Before Drug Holiday
Patients should be on bisphosphonates for 5 years (oral agents) or 3 years (intravenous zoledronic acid) before considering a drug holiday. 1
- The American College of Physicians strongly recommends 5 years as the standard treatment duration for oral bisphosphonates like alendronate and risedronate 1, 2
- For intravenous zoledronic acid, 3 years of treatment is sufficient before reassessing the need for continuation 3, 4
- All patients receiving bisphosphonate therapy should have the need for continued therapy reevaluated periodically after this initial treatment period 1
Who Should Take a Drug Holiday
Patients at low-to-moderate fracture risk should be considered for drug discontinuation after the initial treatment period. 1
Eligible for Drug Holiday (3-5 years off therapy):
- No previous hip or vertebral fractures during treatment 2, 4
- Hip BMD T-score > -2.5 after treatment 2, 4
- No multiple non-spine fractures 4
- Age considerations and stable fracture risk profile 2
Should Continue Treatment (NOT eligible for drug holiday):
- Previous hip or vertebral fractures 2, 4
- Multiple non-spine fractures 4
- Hip BMD T-score ≤ -2.5 despite treatment 2, 4
- Age >80 years 2
- Ongoing glucocorticoid use (≥7.5 mg prednisone daily) 2, 5
- Multiple risk factors for fracture 2
Duration of Drug Holiday
The drug holiday should last 2-5 years depending on the bisphosphonate used and patient risk factors. 6, 3, 4
- Alendronate: Up to 5 years off therapy for low-risk patients 3, 7
- Zoledronic acid: Up to 3 years off therapy 3, 7
- Risedronate: Up to 1 year off therapy (shorter due to lower bone retention) 3, 7
- High-risk patients should have shorter holidays of 1-2 years maximum 2, 6
Monitoring During Drug Holiday
Reassess patients regularly for new fractures, changes in fracture risk profile, and BMD changes, particularly at the femoral neck. 2, 4
- Do NOT perform routine BMD monitoring during the initial 5-year treatment period, but DO monitor during the drug holiday 2
- Evaluate for new fractures clinically at each visit 2
- Reassess fracture risk every 1-3 years during the holiday 8, 4
- Monitor femoral neck T-score changes specifically 2
- Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) supplementation throughout the holiday 2
When to Restart Bisphosphonates
Resume bisphosphonate therapy if any of the following occur during the drug holiday: 2, 4
- A new fracture occurs (any type) 2
- Femoral neck T-score falls to ≤ -2.5 2, 4
- Fracture risk increases significantly based on clinical assessment 2
- Significant BMD decline (≥10% per year) 5
- New high-risk features develop (e.g., initiation of glucocorticoids) 5
Before Restarting:
- Complete any necessary dental work before resuming therapy, as osteonecrosis of the jaw risk increases with cumulative exposure beyond 5 years total treatment 2
- Consider alternative agents (denosumab, anabolic agents) if fracture occurred after ≥18 months of prior bisphosphonate therapy, suggesting treatment failure 2, 5
Critical Pitfalls to Avoid
- Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound vertebral fractures can occur 1, 2
- Do not automatically continue bisphosphonates beyond 5 years without reassessing fracture risk, as this exposes patients to unnecessary rare adverse events (atypical femoral fractures, osteonecrosis of the jaw) without proven additional benefit in low-risk individuals 2, 4
- Do not use denosumab as a switch option during or after a bisphosphonate holiday without understanding that it cannot be stopped without transitioning back to bisphosphonates 2
- Bisphosphonates beyond 5 years reduce vertebral fractures but NOT hip or other non-vertebral fractures, while increasing long-term harm risk 2