What is the recommended duration of bisphosphonate therapy?

Duration of Bisphosphonate Therapy: Evidence-Based Recommendations

For most patients, bisphosphonate therapy should be continued for 3-5 years initially, followed by reassessment of fracture risk to determine whether to continue therapy, with a maximum recommended duration of 10 years for oral bisphosphonates or 6 years for intravenous bisphosphonates. 1

General Recommendations for Bisphosphonate Duration

• The optimal duration of bisphosphonate therapy has not been definitively established in clinical trials 2
• After 5 years of oral bisphosphonate or 3 years of intravenous bisphosphonate therapy, patients should undergo reassessment of fracture risk 1
• Patients at low risk for fracture should be considered for drug discontinuation after 3-5 years of use 2
• Patients who discontinue therapy should have their fracture risk periodically reassessed 2

Risk-Stratified Approach to Treatment Duration

High-Risk Patients

• For patients at high risk of fracture (older age, low hip T-score, previous major osteoporotic fracture, or fracture while on therapy), continuation of treatment for up to 10 years (oral) or 6 years (intravenous) should be considered 1
• For patients with 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 3
• Options for continued treatment include:
  • Continuing the oral bisphosphonate for 7-10 years
  • Switching to an IV bisphosphonate if absorption or adherence is a problem
  • Switching to another class of osteoporosis medication (teriparatide or denosumab) 3

Low-Risk Patients

• For patients at low fracture risk after 3-5 years of bisphosphonate treatment, a drug holiday of 2-3 years can be considered 1
• For patients who are discontinuing glucocorticoid treatment after receiving bisphosphonate therapy, discontinuation of the osteoporosis medication is recommended if fracture risk is assessed to be low 3
• If fracture risk remains elevated, the osteoporosis treatment course should be completed or continued until fracture risk is assessed to be low 3

Monitoring During Drug Holidays

• During a drug holiday, bone health should be reevaluated every 1-3 years 4
• Evaluation should include:
  • Serial bone mineral density measurements
  • Assessment of bone turnover markers
  • Fracture history evaluation 4
• If assessments during the drug holiday show increased risk of fracture, consider reinitiating treatment 4

Special Considerations for Specific Patient Populations

Cancer Patients with Bone Metastases

• For cancer patients with bone metastases, the NCCN Task Force recommends reconsidering continuation of bisphosphonate therapy at 2 years 3
• Continued bisphosphonate treatment should be considered in patients with active cancer or existing bone metastasis 3
• Discontinuation should be considered for patients with no active disease or who have experienced significant deterioration of renal function 3

Multiple Myeloma

• For multiple myeloma patients, therapy with bisphosphonates should be administered monthly for a period of 2 years 3
• At 2 years, physicians should consider stopping bisphosphonates in patients with responsive or stable disease 3
• For patients in whom bisphosphonates were withdrawn after 2 years, the drug should be resumed upon relapse with new-onset skeletal-related events 3

Breast Cancer Adjuvant Therapy

• For postmenopausal women at intermediate or high risk of recurrence, the duration of bisphosphonate treatment should be 3-5 years and only continued after 5 years if indicated by fracture risk 3
• For premenopausal women on adjuvant ovarian suppression, duration of bisphosphonate treatment should not exceed the duration of ovarian suppression unless indicated for low T-score (3-5 years) 3

Risks of Long-Term Bisphosphonate Therapy

• The risk of atypical femoral fracture increases with bisphosphonate therapy duration 1
• The risk of osteonecrosis of the jaw may increase with the duration of antiresorptive therapy 3
• These rare adverse events are generally outweighed by vertebral fracture risk reduction in high-risk patients 1

Rationale for Drug Holidays

• Bisphosphonates accumulate in bone and continue to be released for months or years after treatment is stopped 5
• Studies with risedronate and alendronate suggest persisting antifracture efficacy for 1-2 years after stopping treatment 5
• Meta-analyses have found no significant difference in fracture risk between patients who continued versus discontinued bisphosphonate therapy after 5 years of treatment 6, 7