Bisphosphonate Holidays


As the temperature continues to fall, many Canadians are dreaming of sunny escapes. Let’s talk about one of the only holidays Canadians can go on this year: a bisphosphonate holiday.



Review: Why are bisphosphonates prescribed?


Bisphosphonates are indicated for the treatment of osteoporosis and prevention of fractures. They are considered first-line therapy for those in high-risk categories based on age, sex, and femoral neck T-score. The following charts from Osteoporosis Canada use the CAROC system to assess 10-year fracture risk:



Note that the decision to recommend bisphosphonate therapy in a moderate-risk individual is based on clinical judgement, including a thorough examination of a patient’s medical history. A patient on high-risk medications, or with a history of falls, would likely benefit from bisphosphonate therapy.



Which bisphosphonates are available in Canada?


Alendronate (Fosamax) & Risedronate (Actonel) – daily, weekly, or monthly dosing

Etidronate – cyclical dosing (14 days every 3 months)

Zoledronic Acid (Aclasta, Zometa) – annual IV dose



When should a bisphosphonate holiday be considered?


The FLEX trial assessed BMD and fracture risk in postmenopausal women who had already been on alendronate for 5 years, and then randomized to another 5 years of either alendronate or placebo. The fact that the participants given the placebo had moderately lower BMD and very little difference in fracture risk suggests that the use of alendronate past 5 years in some patients may be unnecessary.


In a moderate-risk individual with no previous fragility fractures, a holiday can be considered after 3 – 5 years of therapy (assuming >80% adherence). Bisphosphonate therapy can be stopped abruptly without tapering down. The ideal candidate is someone who was started on a bisphosphonate solely due to their CAROC score, without additional medication or lifestyle risk factors. Note that in a high-risk individual, or one with fracture history, bisphosphonate holidays are not recommended.



How long should a bisphosphonate holiday last?


Currently, there are no concrete guidelines as to when a bisphosphonate holiday should end. Risedronate is known to have lower bone affinity than other bisphosphonates, so it is suggested that a risedronate holiday should only last 1 year. In a patient taking alendronate or zoledronic acid, a 1 – 3 year holiday may be considered. A 2014 review in Canadian Family Physician suggested that BMD and fracture risk be re-calculated within 2 – 3 years of discontinuation, to assess whether or not to resume bisphosphonate treatment.



Can drug holidays be considered for other drugs used to treat osteoporosis?


No – drug holidays have not been recommended for treatments like Prolia (denosumab) or Selective Estrogen Receptor Modulators.



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References

  1. Black DM, Schwartz AV, Ensrud KE et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006;296(24):2927-38.

  2. Brown JP, Morin S, Leslie W et al. Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician 2014;60(4):324-33.

  3. Hanley DA. Osteoporosis. In: Compendium of Therapeutic Choices. Ottawa, ON: Canadian Pharmacists Association. Updated May 1, 2017. Accessed December 22, 2020.

  4. Papaioannou A, Morin S, Cheung AM et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 2010;182(17):1864-73.

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