When to discontinue alendronate (bisphosphonate) therapy in patients with osteoporosis?

When to Discontinue Alendronate Therapy

Clinicians should consider stopping alendronate after 5 years of treatment unless the patient has a strong indication for continuation, as extending therapy beyond this period reduces vertebral fracture risk but not other fractures, while increasing the risk of rare but serious long-term adverse effects. 1, 2

Primary Decision Point: The 5-Year Mark

After 5 years of alendronate therapy, the decision to continue or discontinue hinges on reassessing fracture risk 1, 2:

• Discontinue if fracture risk is LOW: Patients who have not experienced fractures before or during therapy and whose fracture risk assessment is low should take a drug holiday 1, 3
• Continue if fracture risk remains HIGH or VERY HIGH: Patients with ongoing high fracture risk should continue treatment 1, 2

Specific Criteria for Discontinuation

Favorable candidates for stopping alendronate after 5 years include: 2, 4

• No fractures during treatment
• Femoral neck T-score > -2.5 at time of discontinuation 3, 4
• Age < 80 years (older age is the strongest predictor of fracture after discontinuation) 4
• No ongoing high-dose glucocorticoid use 1

Specific Criteria for Continuation Beyond 5 Years

Continue alendronate beyond 5 years if: 1, 2

• History of vertebral fractures (especially during treatment)
• Femoral neck T-score ≤ -2.5 at discontinuation 3, 4
• Age > 80 years 4
• Ongoing use of aromatase inhibitors or high-dose glucocorticoids (≥7.5 mg prednisone equivalent daily) 1, 2
• Previous fracture on therapy suggesting treatment failure 1

Duration of Drug Holiday

If discontinuing, suggested drug holiday duration is 3-5 years for alendronate 3, after which the patient should be reassessed for fracture risk 1, 2, 3

What NOT to Monitor During Drug Holiday

Do not use the following to guide decisions after discontinuation, as they do not predict fracture risk: 4

• Follow-up DXA measurements at 1 year after stopping
• Bone turnover markers (NTX, BAP) at 1-2 years after stopping

These measurements showed no association with subsequent fracture risk in the FLEX study 4

When to Resume Treatment After Holiday

Restart alendronate if any of the following occur during the drug holiday: 2, 3

• New fracture occurs
• Fracture risk assessment increases
• BMD remains low (femoral neck T-score ≤ -2.5) 3

Critical Safety Considerations for Long-Term Use

Rare but serious adverse effects increase with duration beyond 5 years: 1, 5

• Atypical femoral fractures: Risk increases with prolonged exposure; patients may report prodromal thigh or groin pain weeks to months before fracture 5, 6
• Osteonecrosis of the jaw (ONJ): Risk increases with duration, especially with invasive dental procedures 1, 5

For patients requiring invasive dental procedures, discontinuation should be considered to reduce ONJ risk 5

Evidence on Fracture Risk After Discontinuation

The FLEX study demonstrated that after 5 years of alendronate followed by 5 years of placebo, there was only a modest absolute increase in clinical vertebral fractures (5.3% vs 2.4%) but no difference in morphometric vertebral fractures or non-vertebral fractures 2, 7. Real-world data from Denmark showed no increased risk of any fracture type in patients discontinuing versus continuing alendronate after 5 years 8.

Special Populations

Glucocorticoid-induced osteoporosis: For patients discontinuing glucocorticoids, stop alendronate if fracture risk is assessed as low; otherwise complete the treatment course 1

Cancer survivors: Similar principles apply, though consider ongoing cancer treatments that affect bone health 1