Why is alendronate (Fosamax) typically discontinued after 5 years of treatment?

From the Guidelines

Fosamax (alendronate) is typically discontinued after 5 years of treatment due to the potential for diminishing benefits and increasing risks with long-term use, as recommended by the American College of Physicians 1. After 5 years of treatment, patients have already gained significant fracture risk reduction, and the medication remains active in bone tissue for years after discontinuation, providing ongoing protection. Continuing beyond 5 years offers minimal additional fracture prevention benefits for most patients while potentially increasing the risk of rare but serious side effects such as atypical femur fractures and osteonecrosis of the jaw, as noted in studies 1. However, this recommendation isn't universal - patients at very high fracture risk (such as those with very low bone density, previous fractures, or other significant risk factors) may benefit from longer treatment. Some guidelines suggest that the decision to stop should be based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications 1. After stopping Fosamax, patients should continue calcium and vitamin D supplementation, maintain regular bone density monitoring (typically every 2-3 years), and follow healthy bone practices including weight-bearing exercise. The most recent and highest quality study on this topic is from 2017, which provides a strong recommendation for the treatment of low bone density or osteoporosis to prevent fractures in men and women 1. Key points to consider when making the decision to discontinue Fosamax include:

• The patient's specific fracture risk profile
• The potential benefits and harms of continued treatment
• The patient's preferences and values
• The cost of continued treatment It is essential to individualize the decision to stop Fosamax based on the patient's unique situation and to make this decision in consultation with their healthcare provider.

From the FDA Drug Label

The decrease in the rate of bone resorption indicated by these markers was evident as early as one month and at three to six months reached a plateau that was maintained for the entire duration of treatment with alendronate sodium Long-term treatment of osteoporosis with alendronate sodium 10 mg/day (for up to five years) reduced urinary excretion of markers of bone resorption, deoxypyridinoline and cross-linked N-telopeptides of type I collagen, by approximately 50% and 70%, respectively, to reach levels similar to those seen in healthy premenopausal women

Alendronate (Fosamax) is typically discontinued after 5 years of treatment because long-term treatment has been shown to maintain a plateau in the reduction of bone resorption markers, indicating that the maximal therapeutic effect is achieved within this timeframe 2.

From the Research

Discontinuation of Alendronate (Fosamax) Treatment

Alendronate (Fosamax) is typically discontinued after 5 years of treatment due to several reasons:

• The medication accumulates in bone and is released for months or years after treatment is stopped, providing some residual antifracture reduction 3
• Studies suggest that if treatment is stopped after 3-5 years, there is persisting antifracture efficacy, at least for 1-2 years 3
• The risk of adverse effects, such as osteonecrosis of the jaw and atypical femoral fractures, increases with long-term use of bisphosphonates, including alendronate 3, 4, 5, 6
• Discontinuation of bisphosphonates, including alendronate, should be considered in patients who have been treated for more than 5 years, especially if the fracture risk is low 4

Factors to Consider for Discontinuation

The decision to discontinue alendronate treatment should be based on individual patient factors, including:

• Fracture risk: patients with low fracture risk may be eligible for a drug holiday, while those with high fracture risk may need to continue treatment 3, 4, 5
• Bone mineral density (BMD): patients with stable or improved BMD may be eligible for a drug holiday, while those with low BMD may need to continue treatment 3, 4, 6
• History of fractures: patients with a history of fractures may need to continue treatment, while those without a history of fractures may be eligible for a drug holiday 4, 5

Duration of Drug Holiday

The optimal duration of a drug holiday for alendronate has not been established, but existing data suggest:

• Up to 5 years for alendronate 4, 6
• Regular reassessment of BMD and fracture risk is necessary to determine the need to resume treatment 4, 6