Bisphosphonate Drug Holiday Recommendations
When to Consider a Drug Holiday
Clinicians should consider stopping bisphosphonate treatment after 5 years in patients without strong indications for continuation, as the risk of long-term harms (osteonecrosis of the jaw and atypical femoral fractures) increases with prolonged use while benefits beyond vertebral fracture reduction are limited. 1
Specific Timing Based on Bisphosphonate Type
The FDA label for risedronate explicitly states that for patients at low-risk for fracture, drug discontinuation should be considered after 3 to 5 years of use. 2
Duration Guidelines by Agent:
- Oral bisphosphonates (alendronate, risedronate): Consider drug holiday after 5 years of treatment 1
- Intravenous zoledronic acid: Consider drug holiday after 3 years of treatment 3, 4
- Denosumab: Drug holidays are NOT recommended due to risk of rebound fractures; if discontinued, bisphosphonate therapy must be initiated within 6 months 1, 5
Risk Stratification for Drug Holiday Decision
LOW-RISK patients (eligible for drug holiday):
- No previous hip or vertebral fractures during treatment 1, 4
- Hip BMD T-score > -2.5 after treatment 6, 4, 5
- No new fractures experienced during therapy 5
- Stable bone mineral density 7
HIGH-RISK patients (continue treatment beyond 5 years):
- Previous hip or vertebral fractures 1, 4
- Multiple non-spine fractures 4
- Hip BMD T-score ≤ -2.5 despite treatment 6, 5
- New fractures during therapy 5
The decision should be individualized based on baseline fracture risk, medication type and half-life, duration of treatment, and the balance of benefits versus harms. 1
Duration of Drug Holiday
Recommended Holiday Length by Agent:
- Alendronate: 3-5 years off therapy 6, 5
- Risedronate: 1-2 years off therapy 6, 5
- Zoledronic acid: 3-6 years off therapy 6, 5
The American College of Physicians notes that bisphosphonates provide residual antifracture efficacy for 1-2 years after discontinuation due to bone accumulation. 7
Monitoring During Drug Holiday
- Do NOT perform routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases 1, 8
- During the drug holiday, reassess patients regularly for:
When to Resume Treatment
Resume bisphosphonate therapy if:
- A new fracture occurs during the holiday 5
- Fracture risk increases significantly 5
- BMD remains low (femoral neck T-score ≤ -2.5) 5
Critical Pitfalls to Avoid
- Never discontinue denosumab without immediately starting bisphosphonate therapy (within 6 months), as rebound vertebral fractures can occur 1, 5
- Do not automatically continue bisphosphonates beyond 5 years without reassessing fracture risk, as this exposes patients to unnecessary rare adverse events without proven additional benefit in low-risk individuals 3, 8
- Ensure dental work is completed before initiating or continuing bisphosphonate therapy to reduce osteonecrosis of the jaw risk 1
- Do not treat beyond 10 years (6 years for IV bisphosphonates) except in patients at very high fracture risk 4
Special Considerations
Patients initially treated with anabolic agents (teriparatide, romosozumab) must be offered an antiresorptive agent after discontinuation to preserve gains and prevent serious rebound vertebral fractures. 1
The risk of atypical femoral fractures falls rapidly after bisphosphonates are discontinued, supporting the rationale for drug holidays in appropriate patients. 4