How long do you continue bisphosphonates (bone resorption inhibitors) therapy?

Duration of Bisphosphonate Therapy

For patients at moderate-to-high fracture risk who have completed 5 years of oral bisphosphonate treatment and are continuing glucocorticoid treatment, continuation of active osteoporosis treatment is recommended rather than discontinuing therapy. 1

Risk-Based Approach to Bisphosphonate Duration

• For adults ≥40 years who have completed 5 years of oral bisphosphonate treatment and continue glucocorticoid treatment with moderate-to-high fracture risk, continued active treatment is recommended 1
• Options for continued treatment include:
  • Continuing oral bisphosphonate for up to 10 years total
  • Switching to IV bisphosphonate if absorption or adherence is problematic
  • Switching to another class of osteoporosis medication (teriparatide or denosumab) 1
• For patients who discontinue glucocorticoid treatment:
  • If assessed to be at low fracture risk: discontinue bisphosphonate but continue calcium and vitamin D 1
  • If assessed to be at moderate-to-high fracture risk: complete the treatment course with the bisphosphonate 1

Duration Considerations Based on Treatment Response

• For patients who experience fracture after ≥18 months of oral bisphosphonate therapy or significant bone mineral density decline (≥10%/year), switching to another class of osteoporosis medication or IV bisphosphonate is recommended 1
• The FDA label for alendronate notes that "patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use" 2
• The optimal duration of bisphosphonate use has not been definitively determined according to the FDA label 2

Drug Holiday Considerations

• For lower-risk patients, a drug holiday of 2-3 years can be considered after 3-5 years of bisphosphonate therapy 3
• During a drug holiday, bone health should be reevaluated every 1-3 years, including bone mineral density measurements 4
• Bisphosphonates create a reservoir in bone that continues to provide some residual anti-fracture effect after discontinuation 5, 6
• Patients who discontinue therapy should have their fracture risk periodically reassessed 2

Risk Considerations for Extended Therapy

• The risk of rare adverse events such as atypical femoral fractures and osteonecrosis of the jaw may increase with longer duration of bisphosphonate therapy 1, 3
• For high-risk patients (older age, low hip T-score, previous major osteoporotic fracture, or fracture while on therapy), the benefits of continued treatment for up to 10 years likely outweigh these rare risks 3, 7
• Extended studies with alendronate (10 years) and zoledronic acid (6 years) have demonstrated continued BMD gains and vertebral fracture risk reduction 7

Special Populations

• For cancer patients with bone metastases, the National Comprehensive Cancer Network recommends reconsidering continuation of bisphosphonate therapy at 2 years 4
• For multiple myeloma patients, bisphosphonate therapy should be administered monthly for a period of 2 years 4
• For postmenopausal women at intermediate or high risk of breast cancer recurrence, the European Society for Medical Oncology recommends bisphosphonate treatment for 3-5 years 4

The decision regarding bisphosphonate duration requires balancing the proven benefits of fracture reduction against the rare but serious risks of prolonged therapy, with consideration of individual patient fracture risk factors and response to treatment.