Predicting Fracture Risk After Alendronate Discontinuation

Summary and Comment |
May 20, 2014

Predicting Fracture Risk After Alendronate Discontinuation

  1. Thomas L. Schwenk, MD

Age and bone density at the time of discontinuation are more accurate predictors than 1-year assessment of bone turnover or bone density.

  1. Thomas L. Schwenk, MD

Because the balance between potential benefits and risks of bisphosphonates becomes less clear after extended use, some authorities recommend interrupting bisphosphonate therapy after about 5 years. However, the best way to follow patients who discontinue these drugs is unknown. In this post hoc analysis, investigators examined fracture data from the Fracture Intervention Trial Long-Term Extension Trial in which postmenopausal women who took alendronate for 5 years were randomized to 5 additional years of alendronate or placebo. All participants underwent assessments of bone-mineral density (BMD) and two markers of bone metabolism (urinary type 1 collagen cross-linked N-telopeptide [NTX] and serum bone-specific alkaline phosphatase [BAP]) at baseline (i.e., after the first 5 years of treatment) and at 1 to 3 years after randomization.

Of the 437 women (median age, 74) who discontinued alendronate after 5 years, 19% experienced ≥1 fractures after the first year of follow-up. Fracture risk increased significantly for every 5-year increment in age. In age-adjusted analyses, risk for fracture in the first year post-alendronate nearly doubled in the lowest tertile of baseline total hip BMD compared with the higher tertiles. No association was found between fracture risk and changes at 1 year in BMD, NTX, or BAP, or at 3 years in bone markers.


Age and BMD response to the first 5 years of alendronate therapy are the best predictors of fracture risk after stopping alendronate. Early BMD or bone-marker testing following discontinuation appears to have no clinical value. Because alendronate has a long biological half-life, delayed monitoring still might have value. Another question, not addressed in this study, is what to do about patients who respond poorly to the first 5 years of therapy.

Editor Disclosures at Time of Publication

  • Disclosures for Thomas L. Schwenk, MD at time of publication Editorial boards UpToDate


Reader Comments (3)

Mary Newburger MD Physician, Family Medicine/General Practice, Retired

What was the fracture rate in the women who continued Alendronate another 5 years? Was it less than in the ones who continued it?

ji Medical Student, Other, korea


DALE SOUTH Physician, Family Medicine/General Practice, retired

my wife discontinued alendronate after about 12 years use 2 years ago and has had no symptoms or increased pain as of now.

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