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Selective Serotonin Reuptake Inhibitors and Other Antidepressants and Risk of Fracture

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Abstract

Our aim was to study fracture risk in users of various antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, and the group of other antidepressants including monoamine oxidase B inhibitors and drugs with effect on the norepinephrine system) and its relationship with effects on inhibition of the cholinergic and serotonin transporter system. We conducted a case-control study with 124,655 fracture cases and 373,962 age- and gender-matched controls. The exposure was use of antidepressants and a number of confounders. Among the tricyclic antidepressants, amitriptyline and clomipramine were associated with a dose-dependent increase in fracture risk, while imipramine and nortriptyline were not. Amityriptyline was associated with an increased risk of fractures at low doses, while the other tricyclic antidepressants were not. Among the selective serotonin reuptake inhibitors, citalopram, fluoxetine, and sertraline were associated with a dose-dependent increase in fracture risk, while the increase was borderline statistically insignificant for paroxetine. The group of other antidepressants was not associated with fracture risk. The increase in fracture risk was significantly associated with the pharmacodynamic effect on the serotonin transporter system but not on other signaling systems. The effect of antidepressants on the risk of fractures may be linked to their effect on the serotonin transporter system. While selective serotonin receptor uptake inhibitors were associated with an increased fracture risk, tricyclic antidepressants and the group of other antidepressants were not systematically associated with fracture risk.

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Acknowledgments

P. V. designed the study, analyzed the data, raised the funds, and drafted the paper. L. M. and L. R. were involved in designing the study, analyzing and interpreting the data, and drafting and revising the paper. All authors have accepted the final version. P. V. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Danmarks Statistik (Statistics Denmark) is acknowledged for the help without which this project would not have been possible. Research librarian Ms. Edith Clausen is acknowledged for invaluable help with the references. The Danish Medical Research Council granted financial support (grant 22-04-0495).

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  1. Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000, Aarhus C, Denmark

    Peter Vestergaard, Lars Rejnmark & Leif Mosekilde

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  1. Peter Vestergaard
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  2. Lars Rejnmark
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  3. Leif Mosekilde
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Correspondence to Peter Vestergaard.

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Vestergaard, P., Rejnmark, L. & Mosekilde, L. Selective Serotonin Reuptake Inhibitors and Other Antidepressants and Risk of Fracture. Calcif Tissue Int 82, 92–101 (2008). https://doi.org/10.1007/s00223-007-9099-9

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  • DOI: https://doi.org/10.1007/s00223-007-9099-9

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