What if there's no significant improvement in bone health after 5 years of alendronate (bisphosphonate) therapy?

From the Guidelines

If there's no significant improvement in bone health after 5 years of alendronate therapy, a drug holiday should be considered, especially for patients at moderate fracture risk. After 5 years of bisphosphonate treatment, the medication accumulates in bone and continues to provide some protective effect even after discontinuation, as suggested by the American College of Physicians guideline update 1. For patients at high fracture risk (previous hip or vertebral fractures, very low T-scores below -3.0), continuing therapy for up to 10 years may be appropriate, but with reassessment of risks and benefits. During a drug holiday, bone mineral density should be monitored every 2-3 years, and treatment should be restarted if there's significant bone loss, a fracture occurs, or high-risk factors develop. Some key points to consider in the management of patients on long-term bisphosphonate therapy include:

• The potential for rare but serious side effects such as osteonecrosis of the jaw and atypical subtrochanteric fractures, as noted in studies on bisphosphonates 1.
• The importance of ensuring adequate calcium and vitamin D intake, as these are crucial for bone health, regardless of the treatment approach.
• The role of alternative treatments like denosumab (Prolia), teriparatide, or abaloparatide if bisphosphonates have been ineffective, as these offer different mechanisms of action and may be beneficial for patients who do not respond to bisphosphonates.
• Investigation of secondary causes affecting bone health, such as vitamin D deficiency, hyperparathyroidism, or medication effects, which could be contributing to the lack of improvement in bone health. Given the most recent and highest quality evidence from the American College of Physicians guideline update 1, the approach to managing patients with no significant improvement in bone health after 5 years of alendronate therapy should prioritize a drug holiday for those at moderate fracture risk, while considering the individual's overall risk profile and the potential benefits and harms of continued therapy.

From the FDA Drug Label

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

The FDA drug label does not provide guidance on what to do if there is no significant improvement in bone health after 5 years of alendronate therapy.

From the Research

No Significant Improvement in Bone Health After 5 Years of Alendronate Therapy

• If there is no significant improvement in bone health after 5 years of alendronate (bisphosphonate) therapy, transitioning to other therapies should be considered 2.
• Studies have shown that switching to other therapies such as zoledronic acid, strontium ranelate, denosumab, or teriparatide can cause further increases in bone mineral density (BMD) 2.
• However, the decision to switch therapies should be based on individual patient factors, such as age, bone density, and fracture risk 3.
• Age and hip BMD at discontinuation of alendronate therapy are significant predictors of clinical fractures during the subsequent 5 years 3.

Alternative Therapies

• Denosumab has been shown to yield higher additional lumbar spine BMD gain compared to bisphosphonates after stopping teriparatide therapy 4.
• Switching to teriparatide can be considered for a limited time for select patients, but it needs to be followed up with anti-resorptive treatment to prevent loss of bone gained 2.
• Zoledronic acid can maintain therapeutic effects for 12 months after switching from alendronate 2.

Duration of Alendronate Therapy

• The cost-effectiveness of 5 versus 10 years of alendronate treatment prior to a drug holiday has been evaluated, and results suggest that 5 years of treatment may be the more effective and cost-effective option for most postmenopausal women 5.
• However, the optimal duration of alendronate therapy may depend on individual patient factors, such as age and bone density 5.
• Ten years of alendronate therapy has been shown to produce sustained therapeutic effects and was well tolerated in postmenopausal women with osteoporosis 6.