Abstract
Objectives
Bisphosphonates (BPs) might have extra benefits in reducing mortality because of their
anti-atherosclerotic effects, but studies reported conflicting results. We investigated
the association between oral BP use and mortality risk following a major osteoporotic
fracture (MOF) in the United Kingdom.
Design
This was a population-based cohort study.
Setting and Participants
In total, 163,273 adults aged 50 years and older with an MOF between 2000 and 2018
from the Clinical Practice Research Datalink in the United Kingdom.
Methods
Cox proportional hazards models were used to estimate the risk of all-cause mortality
in current (0‒6 months), recent (7‒12 months), and past (>1 year) exposures to oral
BPs after nonhip MOF and hip fracture. In addition, stratification by sex, BP type,
and duration of follow-up was performed.
Results
Compared with never users of oral BPs, current BP use was associated with a 7% higher
all-cause mortality risk after nonhip MOF, whereas a 28% lower all-cause mortality
risk was observed after hip fracture. Past BP exposure was associated with a 14% and
42% lower risk after nonhip MOF and hip fracture, respectively. When considering only
the first 5 years of follow-up, mortality risk associated with current BP use was
significantly lower for both fracture groups, and the greatest reduction in mortality
risk was observed within the first year. Women had slightly lower risk compared with
men.
Conclusions and Implications
We found a slight increased risk of all-cause mortality with current BP exposure after
a nonhip MOF; however, a protective effect was observed following a hip fracture.
Both the timing and the effect size of an association based on the anti-atherosclerotic
hypothesis of BPs are not supported by our results. The decreasing trend of the mortality
risk with shorter durations of follow-up suggests that the observed association is
likely due to unknown distortion or unknown pleiotropic properties of BPs.
Keywords
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Article info
Publication history
Published online: December 12, 2019
Footnotes
Dr. Frank de Vries is the guarantor of this study, accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. He attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
This study was reviewed and approved by the Independent Scientific Advisory Committee of the Clinical Practice Research Datalink (reference 18_115), which is responsible for reviewing protocols for scientific quality.
This research did not receive any funding from agencies in the public, commercial, or not-for-profit sectors.
All authors have completed the ICMJE uniform disclosure form (available on request from the corresponding author) at www.icmje.org/coi_disclosure.pdf and declare: SA, AMB, PG declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.
JvB reports grants and personal fees from Amgen, grants and personal fees from Eli Lilly, and personal fees from UCB, outside the submitted work.
TvS reports grants from GSK, personal fees from Pfizer, and personal fees from Roche, outside the submitted work.
FV supervises 2 PhD students who are employed with F. Hoffmann la Roche Ltd. (Basel, Switzerland/Welwyn Garden City, UK). He has not received any reimbursements for this, and the topic of these PhDs is not related to the current work.
Identification
Copyright
© 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
