Associations between osteoporosis and drug exposure: A post-marketing study of the World Health Organization pharmacovigilance database (VigiBase®).


Journal

Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048

Informations de publication

Date de publication:
12 2021
Historique:
received: 20 04 2021
revised: 13 07 2021
accepted: 28 07 2021
pubmed: 4 8 2021
medline: 26 10 2021
entrez: 3 8 2021
Statut: ppublish

Résumé

Bone remodeling is a complex process, and many conditions (including drug exposure) lead to osteoporosis. Here, we sought to detect new disproportionality signals for drugs associated with osteoporosis. We performed a disproportionality analysis of the World Health Organization's VigiBase® pharmacovigilance database through April 12, 2020. The frequency of reports on osteoporosis for all identified drug classes was compared with that for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. Of the 7,594,968 cases spontaneously recorded to VigiBase®, 4758 concerned osteoporosis. New disproportionality signals with a pharmacologically plausible mechanism were found for drugs used in neurology (levodopa (ROR [95%CI]: 10.18 [4.33-25.10]), selective serotonin agonists (4.22 [2.34-7.00]) and memantine (4.10 [1.56-8.93])), hematology (romiplostim (4.93 [1.15-21.10])), pulmonology (macitentan (3.02 [1.84-4.90])), ophthalmology (ranibizumab (3.31 [1.00-10.51])) and rheumatology (tofacitinib (3.65 [3.00-4.40])). The robustness of these new results is supported by the significant RORs for the vast majority of drugs already known to induce osteoporosis and/or increase the fracture risk, namely glucocorticoids, gonadotropin-releasing hormone analogs, anti-aromatases, androgen receptor blockers, thyroid hormones, proton pump inhibitors, thiazolidinediones, vitamin K antagonists, loop diuretics, protease inhibitors, nucleoside and nucleotide reverse transcriptase inhibitors, and enzyme-inducing antiepileptics including barbiturates and derivatives, hydantoin derivatives, carboxamide derivatives and fatty acid derivatives. We established up a comprehensive list of drugs potentially associated with osteoporosis and highlighted those with pharmacologically plausible mechanisms leading to bone fragility. Our results might pave the way for additional exploration of these mechanisms.

Sections du résumé

BACKGROUND
Bone remodeling is a complex process, and many conditions (including drug exposure) lead to osteoporosis. Here, we sought to detect new disproportionality signals for drugs associated with osteoporosis.
METHODS
We performed a disproportionality analysis of the World Health Organization's VigiBase® pharmacovigilance database through April 12, 2020. The frequency of reports on osteoporosis for all identified drug classes was compared with that for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)].
RESULTS
Of the 7,594,968 cases spontaneously recorded to VigiBase®, 4758 concerned osteoporosis. New disproportionality signals with a pharmacologically plausible mechanism were found for drugs used in neurology (levodopa (ROR [95%CI]: 10.18 [4.33-25.10]), selective serotonin agonists (4.22 [2.34-7.00]) and memantine (4.10 [1.56-8.93])), hematology (romiplostim (4.93 [1.15-21.10])), pulmonology (macitentan (3.02 [1.84-4.90])), ophthalmology (ranibizumab (3.31 [1.00-10.51])) and rheumatology (tofacitinib (3.65 [3.00-4.40])). The robustness of these new results is supported by the significant RORs for the vast majority of drugs already known to induce osteoporosis and/or increase the fracture risk, namely glucocorticoids, gonadotropin-releasing hormone analogs, anti-aromatases, androgen receptor blockers, thyroid hormones, proton pump inhibitors, thiazolidinediones, vitamin K antagonists, loop diuretics, protease inhibitors, nucleoside and nucleotide reverse transcriptase inhibitors, and enzyme-inducing antiepileptics including barbiturates and derivatives, hydantoin derivatives, carboxamide derivatives and fatty acid derivatives.
CONCLUSION
We established up a comprehensive list of drugs potentially associated with osteoporosis and highlighted those with pharmacologically plausible mechanisms leading to bone fragility. Our results might pave the way for additional exploration of these mechanisms.

Identifiants

pubmed: 34343739
pii: S8756-3282(21)00302-1
doi: 10.1016/j.bone.2021.116137
pii:
doi:

Substances chimiques

Pharmaceutical Preparations 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

116137

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Auteurs

Benjamin Batteux (B)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France; Department of Rheumatology, Saint-Quentin Medical Center, F-02321 Saint-Quentin, France; MP3CV Laboratory, EA7517, Jules Verne University of Picardie, F-80054 Amiens, France; RECIF, Amiens-Picardie University Medical Center, F-80054 Amiens, France. Electronic address: batteux.benjamin@chu-amiens.fr.

Youssef Bennis (Y)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France; MP3CV Laboratory, EA7517, Jules Verne University of Picardie, F-80054 Amiens, France.

Sandra Bodeau (S)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France; MP3CV Laboratory, EA7517, Jules Verne University of Picardie, F-80054 Amiens, France.

Kamel Masmoudi (K)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France.

Anne-Sophie Hurtel-Lemaire (AS)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France.

Said Kamel (S)

MP3CV Laboratory, EA7517, Jules Verne University of Picardie, F-80054 Amiens, France; Biochemistry Laboratory, Amiens University Medical Center, F-80000 Amiens, France.

Valérie Gras-Champel (V)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France; MP3CV Laboratory, EA7517, Jules Verne University of Picardie, F-80054 Amiens, France.

Sophie Liabeuf (S)

Department of Pharmacology, Amiens University Medical Center, F-80054 Amiens, France; MP3CV Laboratory, EA7517, Jules Verne University of Picardie, F-80054 Amiens, France.

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