Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial

Background Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatmen...

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Main Authors: Jolien Geers, Rong Bing, Tania A. Pawade, Mhairi K. Doris, Marwa Daghem, Alexander J. Fletcher, Audrey C. White, Laura Forsyth, Emily Evans, Jacek Kwieciński, Michelle C. Williams, Edwin J. R. van Beek, Soongu Kwak, Frederique E.C.M. Peeters, Evangelos Tzolos, Piotr J Slomka, Christophe Lucatelli, Stuart H. Ralston, Bernard Prendergast, David E. Newby, Marc R. Dweck
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Language:English
Published: Wiley 2024-09-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.123.032571
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author Jolien Geers
Rong Bing
Tania A. Pawade
Mhairi K. Doris
Marwa Daghem
Alexander J. Fletcher
Audrey C. White
Laura Forsyth
Emily Evans
Jacek Kwieciński
Michelle C. Williams
Edwin J. R. van Beek
Soongu Kwak
Frederique E.C.M. Peeters
Evangelos Tzolos
Piotr J Slomka
Christophe Lucatelli
Stuart H. Ralston
Bernard Prendergast
David E. Newby
Marc R. Dweck
author_facet Jolien Geers
Rong Bing
Tania A. Pawade
Mhairi K. Doris
Marwa Daghem
Alexander J. Fletcher
Audrey C. White
Laura Forsyth
Emily Evans
Jacek Kwieciński
Michelle C. Williams
Edwin J. R. van Beek
Soongu Kwak
Frederique E.C.M. Peeters
Evangelos Tzolos
Piotr J Slomka
Christophe Lucatelli
Stuart H. Ralston
Bernard Prendergast
David E. Newby
Marc R. Dweck
author_sort Jolien Geers
collection DOAJ
description Background Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. Methods and Results In a double‐blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F‐sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24‐month change in coronary calcium score, and 12‐month changes in thoracic aorta calcium score, coronary and aortic 18F‐sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [−64 to 148] Agatston units) and either denosumab (94 [0–212] Agatston units, P=0.24) or alendronic acid (34 [−62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22–512] Agatston units) and either denosumab (118 [11–340], P=0.75) or alendronic acid (116 [26–498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F‐sodium fluoride activity between treatment groups. Conclusions Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. registration https://www.clinicaltrials.gov; Unique identifier: NCT02132026.
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spelling doaj-art-4f7a7d04a66b432a8697c04e1d27cc5f2025-08-20T02:07:06ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-09-01131810.1161/JAHA.123.032571Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled TrialJolien Geers0Rong Bing1Tania A. Pawade2Mhairi K. Doris3Marwa Daghem4Alexander J. Fletcher5Audrey C. White6Laura Forsyth7Emily Evans8Jacek Kwieciński9Michelle C. Williams10Edwin J. R. van Beek11Soongu Kwak12Frederique E.C.M. Peeters13Evangelos Tzolos14Piotr J Slomka15Christophe Lucatelli16Stuart H. Ralston17Bernard Prendergast18David E. Newby19Marc R. Dweck20BHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKEdinburgh Clinical Trials Unit University of Edinburgh Edinburgh UKEdinburgh Clinical Research Facility University of Edinburgh Edinburgh UKDepartment of Interventional Cardiology and Angiology Institute of Cardiology Warsaw PolandBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKDepartment of Internal Medicine Seoul National University Hospital Seoul South KoreaMaastricht University Medical Centre Maastricht The NetherlandsBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKDepartments of Biomedical Sciences and Medicine Cedars‐Sinai Medical Center Biomedical Imaging Research Institute Los Angeles CA USAEdinburgh Clinical Research Facility University of Edinburgh Edinburgh UKInstitute of Genetics and Molecular Medicine University of Edinburgh UKSt Thomas’ Hospital and Cleveland Clinic London London UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UKBackground Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. Methods and Results In a double‐blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F‐sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24‐month change in coronary calcium score, and 12‐month changes in thoracic aorta calcium score, coronary and aortic 18F‐sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [−64 to 148] Agatston units) and either denosumab (94 [0–212] Agatston units, P=0.24) or alendronic acid (34 [−62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22–512] Agatston units) and either denosumab (118 [11–340], P=0.75) or alendronic acid (116 [26–498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F‐sodium fluoride activity between treatment groups. Conclusions Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. registration https://www.clinicaltrials.gov; Unique identifier: NCT02132026.https://www.ahajournals.org/doi/10.1161/JAHA.123.032571alendronatecomputed tomographydenosumabpositron emission tomographyvascular calcification
spellingShingle Jolien Geers
Rong Bing
Tania A. Pawade
Mhairi K. Doris
Marwa Daghem
Alexander J. Fletcher
Audrey C. White
Laura Forsyth
Emily Evans
Jacek Kwieciński
Michelle C. Williams
Edwin J. R. van Beek
Soongu Kwak
Frederique E.C.M. Peeters
Evangelos Tzolos
Piotr J Slomka
Christophe Lucatelli
Stuart H. Ralston
Bernard Prendergast
David E. Newby
Marc R. Dweck
Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
alendronate
computed tomography
denosumab
positron emission tomography
vascular calcification
title Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial
title_full Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial
title_fullStr Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial
title_full_unstemmed Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial
title_short Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial
title_sort effect of denosumab or alendronate on vascular calcification secondary analysis of saltire2 randomized controlled trial
topic alendronate
computed tomography
denosumab
positron emission tomography
vascular calcification
url https://www.ahajournals.org/doi/10.1161/JAHA.123.032571
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