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Osteoporos Int. 2019 Jul 31. doi: 10.1007/s00198-019-05097-1. [Epub ahead of print]

Bisphosphonates and mortality: confounding in observational studies?

Author information

1
Unit of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, 90187, Umeå, Sweden.
2
Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, 90187, Umeå, Sweden.
3
School of Sport Sciences, UiT Arctic University of Norway, Postboks 1621, 9509, Alta, Norway.
4
Department of Care Sciences, Malmö University, 20506, Malmö, Sweden.
5
Division of Clinical geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Plan 7, 14183, Huddinge, Sweden.
6
Theme Aging, Karolinska Univeristy Hospital, 14186, Stockholm, Sweden.
7
Research and Development Unit, Stockholm Sjukhem, Mariebergsgatan 22, 11219, Stockholm, Sweden.
8
Unit of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, 90187, Umeå, Sweden. peter.nordstrom@umu.se.

Abstract

Numerous observational studies suggest that bisphosphonates reduce mortality. This study showed that bisphosphonate use is associated with lower mortality within days of treatment, although the association was not significant until the second week. Such an early association is consistent with confounding, although an early treatment effect cannot be ruled out.

INTRODUCTION:

The purpose of this study was to examine whether confounding explains why numerous observational studies show that bisphosphonate use is associated with lower mortality. To this end, we examined how soon after treatment initiation a lower mortality rate can be observed. We hypothesized that, due to confounding, the association would be observed immediately.

METHODS:

This was a retrospective cohort study of hip fracture patients discharged from Swedish hospitals between 1 July 2006 and 31 December 2015. The data covered 260,574 hip fracture patients and were obtained from the Swedish Hip Fracture Register and national registers. Of the 260,574 patients, 49,765 met all eligibility criteria and 10,178 were pair matched (bisphosphonate users to controls) using time-dependent propensity scores. The matching variables were age, sex, diagnoses, prescription medications, type of hip fracture, type of surgical procedure, known or suspected dementia, and physical functioning status.

RESULTS:

Over a median follow-up of 2.8 years, 2922 of the 10,178 matched patients died. The mortality rate was 7.9 deaths per 100 person-years in bisphosphonate users and 9.4 deaths in controls, which corresponded to a 15% lower mortality rate in bisphosphonate users (hazard ratio 0.85, 95% confidence interval 0.79-0.91). The risk of death was lower in bisphosphonate users from day 6 of treatment, although the association was not significant until the second week.

CONCLUSION:

Bisphosphonate use was associated with lower mortality within days of treatment initiation. This finding is consistent with confounding, although an early treatment effect cannot be ruled out.

KEYWORDS:

Bisphosphonates; Death; Mortality; Observational study; Osteoporosis

PMID:
31367949
DOI:
10.1007/s00198-019-05097-1

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