When to stop Alendronate (Alendronate sodium) therapy?

When to Stop Alendronate Therapy

Alendronate therapy should generally be discontinued after 5 years for most patients, with continued treatment beyond 5 years only considered for patients at very high fracture risk. 1

Duration of Treatment Recommendations

• The American College of Physicians (ACP) recommends treating osteoporotic women with pharmacologic therapy for 5 years, after which the benefits of continued therapy should be reassessed 1
• For patients with very high fracture risk (prior osteoporotic fractures, BMD T-score ≤−3.5, or high FRAX scores), continuing alendronate beyond 5 years may be beneficial 1
• After discontinuing alendronate following 5 years of treatment, there is a modest absolute increase in clinical vertebral fractures (5.3% vs 2.4%) but no significant difference in morphometric vertebral fractures or non-vertebral fractures 1

Assessment for Treatment Discontinuation

• Before stopping alendronate, perform a comprehensive fracture risk reassessment including:

  • BMD measurement with vertebral fracture assessment (VFA) or spinal x-ray 1
  • Updated FRAX score (for patients ≥40 years) 1
  • Evaluation of any new fractures since treatment initiation 1

• Factors favoring continuation beyond 5 years:

  • Very high fracture risk: prior osteoporotic fracture(s), BMD T-score ≤−3.5, FRAX 10-year risk of major osteoporotic fracture ≥30% or hip ≥4.5% 1
  • Ongoing high-dose glucocorticoid therapy (≥30 mg/day for >30 days or cumulative doses ≥5 g/year) 1
  • Significant bone loss during treatment 1

Residual Effects After Discontinuation

• Alendronate has a residual effect on bone mass after treatment withdrawal 2
• The efficacy in preventing bone loss is proportional to the duration of treatment, with effects persisting up to 7 years after discontinuation 2
• After stopping alendronate, the rate of bone loss corresponds to the normal postmenopausal rate of bone loss 2

Monitoring After Discontinuation

• BMD with VFA or spinal x-ray should be performed every 1-2 years after osteoporosis therapy is discontinued 1
• Current evidence does not support bone density monitoring during the 5-year pharmacologic treatment period 1
• Bone turnover markers tend to reverse back to normal levels after discontinuation but may remain affected for several years 2

Risks of Long-Term Therapy

• Prolonged bisphosphonate use raises concerns about potential adverse effects of chronic suppression of bone turnover 1
• Rare but serious adverse events associated with long-term bisphosphonate use include:
  • Atypical subtrochanteric femoral fractures 3
  • Osteonecrosis of the jaw (ONJ), particularly in patients undergoing invasive dental procedures 3
  • These risks, while uncommon, increase with duration of exposure 1

Special Considerations

• For patients on glucocorticoid therapy: Those who discontinue alendronate but continue taking glucocorticoids (>6 mg/day) may experience substantial loss of BMD in the lumbar spine and hip 4
• For patients with continued risk factors for bone loss (e.g., ongoing aromatase inhibitor use for breast cancer), the optimal duration may need to be extended 1

Algorithm for Decision-Making

1. Complete 5 years of alendronate therapy
2. Reassess fracture risk with BMD measurement and clinical risk factors
3. If patient has very high fracture risk (prior fractures, T-score ≤−3.5, very high FRAX score), consider continuing therapy
4. If patient has moderate-to-low fracture risk, discontinue alendronate
5. Monitor BMD every 1-2 years after discontinuation
6. Resume therapy if significant bone loss occurs or new fractures develop