When to Take Alendronate Drug Holiday
Bisphosphonate drug holidays should be considered after 5 years of alendronate therapy for most patients, with continuation only for those at very high fracture risk. 1
Patient Risk Stratification for Drug Holiday Decisions
Patients Who Should Continue Alendronate Beyond 5 Years
- Patients at very high fracture risk:
Patients Who Should Take a Drug Holiday After 5 Years
- Patients with moderate to low fracture risk
- Patients who have shown good response to therapy
- Patients with stable or improved BMD measurements
- Patients without recent fractures 1
Duration of Drug Holiday
The American College of Physicians recommends considering stopping bisphosphonate treatment after 5 years due to increased risk of long-term harms 1. The optimal duration of the drug holiday depends on the specific bisphosphonate used:
- Alendronate: Up to 3-5 years drug holiday 3
- Zoledronic acid: Up to 3 years drug holiday 3
- Risedronate: Up to 1 year drug holiday 3
This difference in duration reflects the varying half-lives of these medications, with risedronate having a shorter half-life than alendronate, resulting in potentially shorter residual fracture protection during a drug holiday 4.
Monitoring During Drug Holiday
Regular monitoring is essential during a bisphosphonate drug holiday:
- Bone Mineral Density (BMD): Reassess after 1-2 years of drug holiday
- Bone Turnover Markers: Monitor for increases that may indicate loss of bisphosphonate effect
- Fracture Risk Assessment: Regularly evaluate using risk assessment tools
- Clinical Evaluation: Watch for height loss, back pain, or other signs of vertebral fractures 1
When to Resume Bisphosphonate Therapy
Treatment should be resumed if any of the following occur during the drug holiday:
- New fracture
- Significant BMD decline (>5% at hip)
- Increase in fracture risk factors
- T-score falls to ≤ -2.5 1
- Bone turnover markers return to pre-treatment levels 5
Special Considerations
Atypical Femoral Fractures
Drug holidays are particularly important for reducing the risk of atypical femoral fractures (AFFs), which are associated with long-term bisphosphonate use. These fractures can occur anywhere in the femoral shaft with minimal trauma and are often preceded by prodromal thigh pain 6.
Osteonecrosis of the Jaw
Another concern with long-term bisphosphonate use is osteonecrosis of the jaw (ONJ). Risk factors include invasive dental procedures, cancer diagnosis, poor oral hygiene, and concomitant therapies like chemotherapy or corticosteroids 6. The risk of ONJ increases with duration of bisphosphonate exposure 2.
Fracture Risk During Drug Holiday
Recent research indicates that discontinuing alendronate beyond 2 years is associated with increased risk of hip, humerus, and clinical vertebral fractures compared to continuing therapy 7. A study comparing drug holidays after long-term risedronate versus alendronate therapy found that risedronate drug holidays were associated with a small increase in risk for hip fracture compared with alendronate drug holidays (HR, 1.18 [95% CI, 1.04 to 1.34]) 4.
Clinical Decision Algorithm
- Assess baseline fracture risk before considering drug holiday
- If patient has taken alendronate for ≥5 years:
- Evaluate T-score, fracture history, and other risk factors
- If T-score > -2.5 AND no recent fractures: Initiate drug holiday
- If T-score ≤ -2.5 OR recent fracture: Continue treatment
- During drug holiday:
- Ensure adequate calcium and vitamin D intake
- Monitor BMD every 1-2 years
- Assess for new fractures or risk factors
- Resume treatment if:
- New fracture occurs
- Significant BMD decline
- T-score falls to ≤ -2.5
Remember that the decision regarding bisphosphonate drug holidays must balance the benefits of reducing rare but serious adverse events against the risk of fractures that may occur when treatment is discontinued.