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Grand Rounds

Does Extending Bisphosphate Therapy Beyond 5 Years Lead to Lower Risk of Hip Fracture?

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BACKGROUND AND PURPOSE:

  • Bisphosphate drugs have a known ability to reduce fractures during the first 3 to 5 years of therapy; however, the optimal duration of treatment is unknown
  • Izano et al. (JAMA Network Open, 2020) examined whether continuing this medication for 5 additional years impacts the risk of hip fracture among women

METHODS:

  • Retrospective cohort study
    • Data from Kaiser Permanente Northern and Southern California
  • Participants
    • Women were between 45 to 80 years at bisphosphonate initiation | At least 60% adherent to therapy in each of the 5 years after initiation
    • Completed 5 years of treatment by study entry (Jan 1, 2002 to Sep 30, 2014)
    • Bisphosphonates: Alendronate, risedronate, or ibandronate
  • Study design
    • Patients were grouped into 3 discontinuation timeframes (following completion of the initial 5 years)
    • 2 additional years
    • 5 additional years
  • Primary outcomes
    • Hip fracture

RESULTS:

  • 29,685 women
    • Mean (IQR) age: 71 (64 to 77) years
    • 60% non-Hispanic white
    • Hip fractures: 507 incidents
  • Compared with discontinuation at study entry, there were no differences in the risk of hip fracture if women remained on therapy for
    • 2 additional years
      • 5-year risk difference (RD) −2.2 per 1000 individuals (95% CI, −20.3 to 15.9)
    • 5 additional years
      • 5-year RD 3.8 per 1000 individuals (95% CI, −7.4 to 15.0)
  • There were no significant differences in hip fracture risk between 5 additional years and 2 additional years of treatment
    • 5-year RD 6.0 per 1000 individuals (95% CI, −9.9 to 22.0)
  • Interim hip fracture risk appeared lower if women discontinued after 2 additional years, but not without a 6-month grace period (additional 6 months before calling the case discontinued)
    • 3-year RD 2.8 per 1000 individuals (95% CI, 1.3 to 4.3)
    • 4-year RD 9.3 per 1000 individuals (95% CI, 6.3 to 12.3)

CONCLUSION:

  • For women that had already completed 5 years of bisphosphate therapy, there was no difference in hip fracture risk if they discontinued therapy at 5 years, 7 years, or 10 years (total)
  • The authors conclude that

Our findings of hip fracture risk are similar to the FLEX randomized clinical trial, in which overall clinical fracture risk was not significantly different between those who took placebo or alendronate for an additional 5 years

Learn More – Primary Sources:

Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women

Fracture Prediction After Discontinuation of 4 to 5 Years of Alendronate TherapyThe FLEX Study

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Related ObG Topics:

Osteoporosis Treatment for Postmenopausal Women at High Risk for Fracture
Hip Fractures in Older Women: Who is at Risk and Would Benefit Most from Treatment?
Does Combined Vitamin D and Calcium Supplementation Reduce Risk of Fracture?
Is Physical Activity Associated with Lower Risk of Fractures in Older Women?

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