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Drug holiday from bisphosphonates

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Data suggest that following after bisphosphonate exposure of 3 to 5 years in postmenopausal women with osteoporosis:

  • the protection from fractures persists for an unknown interval of time in selected patients when therapy is withdrawn; that the protection wanes within 3 to 5 years of discontinuation; and that the risk of atypical femoral fractures increases with the duration of therapy but may decrease upon withdrawal of treatment

  • bisphosphonates is analogs of pyrophosphate having a three-dimensional structure capable of chelating divalent cations such as Ca2+
    • bisphosphonates have a strong affinity for bone, targeting especially bone surfaces undergoing remodelingand binds strongly to hydroxyapatite and remains inactive until the bone containing BP are reabsorbed half-life after incorporation into mineralized bone nearly 10 years (1)

A. Determination of the duration for bisphosphonate therapy (2,3)

  • i. Drug holiday from alendronate and risedronate may be considered after 5 years

  • ii. Drug holiday from zoledronic acid may be considered after 3 years

B. Selection of the appropriate candidates for the drug holiday

  • i. Consider a drug holiday after 5 years of alendronate and risedronate treatment, and after 3 years of zoledronic acid, in individuals without high risk.

  • ii. Consider the continued treatment in individuals with high risk.
    • 1) T-score at any site still <=-2.5 after bisphosphonate therapy (5 years for alendronate and risedronate, and 3 years for zoledronic acid).
    • 2) Previous fracture of the hip or spine.
    • 3) High risk of fracture because of secondary osteoporosis from chronic diseases or medication.

  • iii. Alternative therapy may be used for individuals with high risk

  • iv. Factors guiding the determination of a drug holiday are the variable anti-resorptive potency and binding affinity of each bisphosphonate, as well as a demonstration of compliance with the therapy

Duration and Monitoring during a drug holiday (2,3,4)

Duration of treatment and the length of the 'holiday' should be tailored to individual patient circumstances and based on individual assessments of risk and benefit

  • it has been stated that "..a drug holiday of 1-2 years should be considered after 3-5 years of bisphosphonate therapy except in those patients who remain at very high fracture risk.." (4)

A. Parameter for monitoring during a drug holiday

  • i. Consider the annual measurement of BMD using dual energy X-ray absorptiometry.

B. Restart therapy after a drug holiday

  • i. Consider re-treatment if there is a significant decrease in BMD.
  • ii. Consider re-treatment if T-score reaches <= -2.5 or a new osteoporotic fracture occurs


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