What is the duration of a drug holiday for patients on Fosamax (alendronate)?

Duration of Fosamax (Alendronate) Drug Holiday

After 5 years of alendronate treatment, patients at low-to-moderate fracture risk should take a drug holiday of up to 5 years, while high-risk patients should continue therapy or take a shorter holiday of 1-2 years with close monitoring. 1, 2, 3

Initial Treatment Duration Before Drug Holiday

• Treat for 5 years before considering discontinuation in most osteoporotic patients, as recommended by the American College of Physicians 1
• The FDA label explicitly states that patients at low fracture risk should be considered for drug discontinuation after 3-5 years of use 3
• All patients on bisphosphonate therapy require periodic re-evaluation for the need to continue treatment 3

Drug Holiday Duration Based on Risk Stratification

Low-to-Moderate Risk Patients

• Drug holiday can extend up to 5 years after completing 5 years of alendronate therapy 4, 5
• These patients can remain off therapy as long as bone mineral density (BMD) remains stable and no fractures occur 6
• After discontinuation, there is only a modest absolute increase in clinical vertebral fractures, with no significant difference in morphometric vertebral fractures or non-vertebral fractures 2

High-Risk Patients (Should NOT Take Extended Holidays)

• Continue therapy beyond 5 years OR take a holiday of no more than 1-2 years 6, 5
• High-risk factors favoring continuation include: T-score ≤ -2.5, prevalent vertebral fractures, ongoing high-dose glucocorticoid therapy (≥7.5 mg prednisone daily equivalent), or significant bone loss during treatment 2, 5
• Five years of alendronate was insufficient in preventing vertebral fractures in high-risk patients during drug holidays 4
• Resurgent bone turnover becomes problematic in high-risk patients, with fractures recurring as early as 12 months following discontinuation 4

Pre-Holiday Assessment Requirements

Before stopping alendronate, perform comprehensive fracture risk reassessment including:

• BMD measurement with vertebral fracture assessment (VFA) or spinal x-ray 2
• Updated FRAX score calculation 2
• Review of additional risk factors: older age, low hip BMD, underweight status, low medication adherence, and prevalent/incident fractures 4

Monitoring During Drug Holiday

• Perform BMD with VFA or spinal x-ray every 1-2 years after discontinuation 2
• Monitor for increases in bone turnover markers (BTMs) and reductions in BMD, which are generally observed during holidays 4
• Lumbar spine BMD typically decreases approximately 1.5% over 5 years, while femur BMD decreases less than 3% over 5 years 7

Pharmacologic Rationale for Extended Holidays

• Alendronate has a skeletal half-life exceeding 10 years due to high bone retention and slow release during bone resorption 7
• This prolonged retention provides continued antifracture efficacy for 1-2 years after stopping treatment 6
• The drug accumulates in bone, creating a reservoir that continues releasing for months or years after discontinuation 3, 6

Critical Caveats

• These recommendations apply specifically to alendronate and cannot be extrapolated to other bisphosphonates due to molecular differences in affinity and antiresorptive potency 7
• Zoledronic acid confers more durable fracture reduction (holidays up to 3 years), while risedronate shows faster offset of effect (holidays only 1 year) 4, 5
• Drug holidays aim to reduce rare adverse events (atypical femoral fractures and osteonecrosis of the jaw) while maintaining fracture protection, though direct evidence that holidays reduce these complications is lacking 4, 8