Duration of Bisphosphonate Therapy Before Taking a Drug Holiday
Bisphosphonate therapy should be limited to 3-5 years before considering a drug holiday for most patients with osteoporosis. 1, 2, 3
Evidence-Based Recommendations
The optimal duration of bisphosphonate therapy depends on several factors, but current guidelines consistently recommend:
- For patients at low-risk for fracture: Consider drug discontinuation after 3-5 years 1, 2, 3
- For patients at high-risk for fracture (T-score ≤ -2.5 or previous fractures): Consider longer treatment (up to 10 years) with periodic reassessment 1, 4
Drug-Specific Considerations
Different bisphosphonates have varying half-lives in bone, affecting the recommended duration of drug holidays:
Alendronate
- Treatment duration: 3-5 years for most patients 2
- Drug holiday duration: Up to 5 years with monitoring 4, 5
- Residual effect: Continued anti-fracture efficacy for 1-2 years after discontinuation 4
Risedronate
- Treatment duration: 3-5 years 3
- Drug holiday duration: 1-2 years (shorter than alendronate due to faster offset) 5, 6
- Residual effect: Sustained effect through 5 years, with evidence suggesting benefit through 7 years 4
Zoledronic Acid
- Treatment duration: 3-5 years 1
- Drug holiday duration: Up to 3 years 5, 6
- Residual effect: Most durable reduction in fractures, particularly after six annual infusions 6
Risk Stratification for Drug Holiday Decisions
High-Risk Patients (Not Ideal for Drug Holiday)
- T-score ≤ -2.5 at femoral neck after treatment
- History of vertebral or hip fracture
- Older age (>70 years)
- Current use of medications that increase fracture risk (e.g., glucocorticoids)
- New fractures while on therapy
Low-Risk Patients (Good Candidates for Drug Holiday)
- T-score > -2.5
- No history of fractures
- Younger age
- Stable or improved BMD on treatment
Monitoring During Drug Holiday
- Bone mineral density testing: Every 1-2 years 7
- Bone turnover markers: Consider to assess return of bone resorption
- Fracture risk reassessment: Regular evaluation for new risk factors
- Resume therapy if: BMD significantly decreases, bone turnover markers significantly increase, or new fracture occurs 1, 8
Rationale for Drug Holidays
Drug holidays are recommended primarily to reduce the risk of rare but serious adverse events associated with long-term bisphosphonate use:
- Atypical femoral fractures (3.0-9.8 cases per 100,000 patient-years) 7, 6
- Osteonecrosis of the jaw (less than 1 case per 100,000 person-years) 7
Important Caveats
- Bisphosphonates accumulate in bone and continue to be released for months to years after discontinuation 4
- The risk of rebound fractures varies by medication, with denosumab having the highest risk (not a bisphosphonate but important to note) 8
- Patients on drug holidays should maintain adequate calcium and vitamin D intake 1
Remember that the decision to initiate a drug holiday should be based on a thorough assessment of the individual patient's fracture risk, response to therapy, and potential for adverse events from continued treatment.