When to take a break from alendronate (bisphosphonate) treatment?

When to Take a Break from Alendronate Treatment

Clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation, as increasing the duration beyond this period likely reduces risk for vertebral fractures but not other fractures while increasing risk for long-term adverse effects. 1

Factors to Consider When Deciding on Alendronate Discontinuation

Baseline Risk Assessment

• Evaluate the patient's current fracture risk based on bone mineral density (BMD), history of fractures, and response to prior alendronate treatment 1
• Age is a significant determinant of fracture risk after discontinuation, with patients over 80 years having nearly three times higher risk compared to those 50-60 years old 2
• Femoral neck T-score at the time of discontinuation is a strong predictor of future fracture risk 3

Indications for Continuing Beyond 5 Years

• Patients with femoral neck T-scores of -2.5 or less after 5 years of treatment benefit from continued therapy with reduced nonvertebral fracture risk 4
• Patients at very high fracture risk may benefit from continuing beyond 5 years 1
• Patients with ongoing risk factors for bone loss, such as continued use of aromatase inhibitors for more than 5 years 1

Indications for Discontinuation (Drug Holiday)

• Patients with T-scores better than -2.5 after 5 years of treatment show no significant reduction in nonvertebral fracture risk with continued therapy 4
• Patients with low fracture risk after initial treatment period 1
• Concerns about long-term adverse effects such as atypical femoral fractures or osteonecrosis of the jaw 1, 5

Long-Term Effects and Persistence After Discontinuation

• After discontinuation of alendronate, BMD remains higher than pre-treatment baseline values for up to 5 years 6
• Bone turnover markers remain suppressed compared to pre-treatment values even after discontinuation 6
• The Fracture Intervention Trial Long-term Extension (FLEX) study showed 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 after discontinuing alendronate for 5 years following 5 years of treatment 1
• A recent population-based cohort study found no increased risk of any fracture, vertebral fracture, hip fracture, or major osteoporotic fracture in patients discontinuing versus continuing alendronate after 5 years of treatment 2

Monitoring After Discontinuation

• Follow-up measurements of BMD one year after discontinuation are not associated with fracture risk and cannot be recommended 3
• Similarly, bone turnover markers (BAP or NTX) measured 1-2 years after discontinuation do not predict fracture risk 3
• The strongest predictors of fracture after discontinuation are age and hip BMD at the time of discontinuation 3

Risks of Long-Term Alendronate Use

• Bisphosphonates are associated with higher risk for osteonecrosis of the jaw and atypical femoral fractures in observational studies, with higher risk after longer treatment duration 1
• Atypical femur fractures can occur with minimal or no trauma and may be bilateral 5
• Patients may report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs 5
• The risk of ONJ may increase with duration of exposure to bisphosphonates 5

Practical Recommendations

• For most patients, consider a drug holiday after 5 years of alendronate therapy 1
• The decision to discontinue should be individualized based on fracture risk factors, medication half-life in bone, and potential benefits versus harms 1
• Patients with T-scores ≤ -2.5 after 5 years of treatment may benefit from continued therapy 4
• For patients who discontinue, no special monitoring of BMD or bone turnover markers in the first few years is necessary as these do not predict fracture risk 3
• If discontinuing alendronate, ensure adequate calcium and vitamin D intake continues 1