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Accepted manuscript

Selective serotonin reuptake inhibitors (SSRIs) and osteoporosis: A target trial emulation using real-world data

Published online by Cambridge University Press:  10 March 2025

Christopher Rohde ,
Lana J. Williams ,
Michael Berk Open the ORCID record for Michael Berk [Opens in a new window]  and
Søren Dinesen Østergaard Open the ORCID record for Søren Dinesen Østergaard [Opens in a new window]
Christopher Rohde
Affiliation:
Department of Affective Disorders, Aarhus University Hospital – Psychiatry, Aarhus, Denmark Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Lana J. Williams
Affiliation:
Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
Michael Berk
Affiliation:
Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
Søren Dinesen Østergaard*
Affiliation:
Department of Affective Disorders, Aarhus University Hospital – Psychiatry, Aarhus, Denmark Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
*
Corresponding author: Søren Dinesen Østergaard, MD PhD, Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, PO Box 281, Geelong, VIC 3220, Australia, E-mail: [email protected], Telephone: +61 34215 3320
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Abstract

Objectives:

Selective serotonin reuptake inhibitors (SSRIs) have been associated with increased risk of osteoporosis, and sertraline may be more potent than citalopram in this regard. Here, target trial emulation was used to investigate whether sertraline, citalopram and escitalopram (the S-enantiomer of citalopram) i) differentially affect the risk of osteoporosis, and ii) increase the risk of osteoporosis in a dose-response-like manner.

Methods:

Danish nationwide registers were used to identify all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram between January 1, 2007, and March 1, 2019. These individuals were followed until development of osteoporosis, death, or end of follow-up. Cox proportional hazards regression was used to adjust for relevant baseline covariates to emulate randomized treatment allocation to compare the rate of osteoporosis for individuals treated with sertraline, citalopram or escitalopram. Subsequently, the cumulative dose of sertraline, citalopram, and escitalopram was calculated, and Cox proportional hazards regression was used to assess dose-response-like relationships with osteoporosis.

Results:

We identified 27,280, 65,529, and 17,703 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. There was no material or statistically significant differential risk of osteoporosis between these groups (hazard rate ratio, HRR=0.98 for citalopram versus sertraline and HRR=0.94 for escitalopram versus sertraline). The results were not indicative of the SSRIs having a dose-response-like effect on osteoporosis risk.

Conclusions:

Sertraline, citalopram and escitalopram do not appear to differentially affect the risk of osteoporosis. The lack of clear dose-response-like relationships suggest that they do not have a causal effect on osteoporosis risk.

Keywords

AntidepressantsSelective Serotonin Reuptake InhibitorsDepressionOsteoporosisEpidemiology
Type
Original Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 23
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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