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Confounding in statistical epidemiology represents a pivotal challenge, referring to the distortion in the perceived relationship between an exposure and an outcome due to the presence of a third variable, known as a confounder. This variable is associated with both the exposure and the outcome but is not a direct link in their causal chain. Its presence can lead to erroneous interpretations of the exposure's effect, either exaggerating or underestimating the true association. This...
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Related Experiment Video

Updated: Jan 21, 2026

Dissociation of the Confounding Influences of Expectancy and Integrative Difficulty Residing in Anomalous Sentences in Event-related Potential Studies
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Bisphosphonates and mortality: confounding in observational studies?

J Bergman1, A Nordström2,3, A Hommel4

  • 1Unit of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, 90187, Umeå, Sweden.

Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
|August 2, 2019
PubMed
Summary

Bisphosphonate use showed a trend toward lower mortality soon after treatment began. While this early association may suggest confounding, an actual treatment effect cannot be excluded.

Keywords:
BisphosphonatesDeathMortalityObservational studyOsteoporosis

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Area of Science:

  • Pharmacology and Geriatric Medicine
  • Bone Metabolism and Osteoporosis Treatment

Background:

  • Observational studies frequently suggest bisphosphonates reduce mortality.
  • The underlying reasons for this association, particularly the role of confounding, require investigation.

Purpose of the Study:

  • To investigate if confounding explains the observed association between bisphosphonate use and reduced mortality.
  • To determine the timing of the mortality reduction following bisphosphonate treatment initiation.

Main Methods:

  • Retrospective cohort study of 10,178 hip fracture patients using time-dependent propensity score matching.
  • Data sourced from Swedish national registers and the Swedish Hip Fracture Register (2006-2015).
  • Matching criteria included age, sex, diagnoses, medications, fracture type, surgery, dementia, and functional status.

Main Results:

  • Bisphosphonate users exhibited a 15% lower mortality rate (HR 0.85; 95% CI 0.79-0.91) over a median 2.8-year follow-up.
  • Lower risk of death observed in bisphosphonate users starting from day 6, though significance was reached in the second week.
  • Mortality rates were 7.9 deaths/100 person-years for users vs. 9.4 for controls.

Conclusions:

  • Bisphosphonate use was linked to reduced mortality within days of starting treatment.
  • The rapid onset of this association supports the possibility of confounding factors.
  • An early, direct treatment effect of bisphosphonates on mortality remains a possibility.