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Assessment of cardiovascular safety of anti-osteoporosis drugs

Assessment of cardiovascular safety of anti-osteoporosis drugs
Assessment of cardiovascular safety of anti-osteoporosis drugs
The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.
0012-6667
1537-1552
Fuggle, Nicholas
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Cooper, Cyrus
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Harvey, Nicholas
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Al-Daghri, Nasser M.
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Brandi, Maria Luisa
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Bruyere, Olivier
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Cano, Antonio
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Dennison, Elaine
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Diez-Pérez, A.
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Kaufman, Jean-Marc
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Palacios, Santiago
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Prieto-Alhambra, D
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Rozenberg, S.
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Thomas, T.
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Trémollieres, Florence
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Rizzoli, René
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Kanis, J. A.
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Reginster, Jean Yves
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Fuggle, Nicholas
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Cooper, Cyrus
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Harvey, Nicholas
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Al-Daghri, Nasser M.
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Brandi, Maria Luisa
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Bruyere, Olivier
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Cano, Antonio
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Dennison, Elaine
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Diez-Pérez, A.
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Kaufman, Jean-Marc
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Palacios, Santiago
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Prieto-Alhambra, D
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Rozenberg, S.
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Thomas, T.
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Trémollieres, Florence
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Rizzoli, René
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Kanis, J. A.
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Reginster, Jean Yves
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Fuggle, Nicholas, Cooper, Cyrus, Harvey, Nicholas, Al-Daghri, Nasser M., Brandi, Maria Luisa, Bruyere, Olivier, Cano, Antonio, Dennison, Elaine, Diez-Pérez, A., Kaufman, Jean-Marc, Palacios, Santiago, Prieto-Alhambra, D, Rozenberg, S., Thomas, T., Trémollieres, Florence, Rizzoli, René, Kanis, J. A. and Reginster, Jean Yves (2020) Assessment of cardiovascular safety of anti-osteoporosis drugs. Drugs, 80 (15), 1537-1552. (doi:10.1007/s40265-020-01364-2).

Record type: Review

Abstract

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

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Manuscript - CV safety resubmission (clean) - Accepted Manuscript
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Accepted/In Press date: 23 June 2020
Published date: 1 October 2020
Additional Information: Funding Information: The ESCEO Working Group was funded by the ESCEO. The ESCEO receives unrestricted educational grants to support its educational and scientific activities from non-governmental organisations, not-for-profit organisations, non-commercial or corporate partners. The choice of topics, participants, content and agenda of the Working Groups as well as the writing, editing, submission and reviewing of the manuscript are the sole responsibility of the ESCEO, without any influence from third parties. Funding Information: NRF, AC, JMK, NA, CC have nothing to disclose. FT reports personal fees for lectures and expertise from Amgen, Arrow, Lilly France, TEVA and Theramex and non-financial support from Besins Healthcare France. MLB reports honoraria from Amgen, Bruno Farmaceutici, Calcilytix and Kyowa Kirin, academic grants and/or speaker fees from Abiogen, Alexion, Amgen, Bruno Farmaceutici, Eli Lilly, Kyowa Kirin, MSD, NPS Pharma, Servier, Shire and Spa and consultancy work for Alexion, Bruno Farmaceutici, Kyowa Kirin, Servier and Shire. SR reports advisory board participation, consultancy work, speakers’ fees and research grants from Mylan, Abbot, Amgen, Ceres and Gilead. NCH reports consultancy work and lecture fees and honoraria from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Servier, Shire, UCB, Kyowa Kirin, Consilient Healthcare, Radius Health and Internis Pharma. DPA’s research group has received research grants from Amgen, Servier and UCB and speaker tuition fees and advisory or consultancy fees (all paid to his department) from Amgen and UCB. TT reports personal fees for lectures and expertise from Amgen, Arrow, Biogen, BMS, Chugai, Expanscience, Gilead, Grunenthal, LCA, Lilly, Medac, MSD, Nordic, Novartis, Pfizer, Sandoz, Sanofi, Theramex, Thuasne, TEVA and UCB and reports financial support or fees for research activities from Amgen, Bone Therapeutics, Chugai, MSD, Novartis, Pfizer and UCB. EMD reports consultancy fees for UCB and Pfizer. JAK reports institutional grant support from Radius Health and Amgen. JYR reports consulting fees or advisory board participation for IBSA-Genevrier, Mylan, Radius Health and Pierre Fabre, lecturing fees for IBSA-Genevrier, Mylan, Cniel and Dairy Research Council (DRC) and grant support from IBSA-Genevrier, Mylan, Cniel and Radius Health. RR reports speaker fees from Abiogen, Amgen, EMF and Sandoz and advisory board fees from Echolight, Mylan, ObsEva, Rejuvenate and Theramex. OB reports grants from Biophytis, IBSA, MEDA, Servier and SMB and personal fees from Amgen, Aptissen, Biophytis, IBSA, MEDA, Sanofi, Servier, SMB and UCB. ADP reports speaker and advisory fees from Amgen, Lilly, Theramex, UCB and Sandoz. Publisher Copyright: © 2020, The Author(s).

Identifiers

Local EPrints ID: 443282
URI: http://eprints.soton.ac.uk/id/eprint/443282
ISSN: 0012-6667
PURE UUID: 855f36ba-ec9a-400d-b391-7ba7b73f651d
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961

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Date deposited: 20 Aug 2020 16:30
Last modified: 26 Nov 2022 05:01

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Contributors

Author: Nicholas Fuggle
Author: Cyrus Cooper ORCID iD
Author: Nicholas Harvey ORCID iD
Author: Nasser M. Al-Daghri
Author: Maria Luisa Brandi
Author: Olivier Bruyere
Author: Antonio Cano
Author: Elaine Dennison ORCID iD
Author: A. Diez-Pérez
Author: Jean-Marc Kaufman
Author: Santiago Palacios
Author: D Prieto-Alhambra
Author: S. Rozenberg
Author: T. Thomas
Author: Florence Trémollieres
Author: René Rizzoli
Author: J. A. Kanis
Author: Jean Yves Reginster

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