Antidepressant Use and Bone Health: Evidence From Mendelian Randomisation.

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Bibliographic Details
Title:	Antidepressant Use and Bone Health: Evidence From Mendelian Randomisation.
Authors:	Huang, Yinqing¹, Lin, Lingzhi², Lin, Mian², Ye, Xiuxiu² yxx20251230@163.com
Source:	Actas Espanolas de Psiquiatria. 2026, Vol. 54 Issue 2, p467-479. 13p.
Subjects:	Antidepressants, Bone health, Genome-wide association studies, Bone metabolism, Causal inference, Osteoporosis, Mendelian randomization, Spontaneous fractures
Abstract:	Background: Antidepressant use has been associated with adverse skeletal outcomes in observational studies, but whether this association is causal remains unclear due to potential confounding factors. This study employed Mendelian randomisation (MR) to systematically evaluate the causal associations between genetically predicted antidepressant use and the risks of osteoporosis and fractures at multiple anatomical sites. Methods: Using publicly available genome-wide association studies (GWAS) datasets, we defined genetically predicted antidepressant use as the exposure and osteoporosis and fractures (spine, leg, and wrist) as outcomes. Genome-wide significant single nucleotide polymorphisms (SNPs) were selected as instrumental variables following dataset harmonisation. The inverse-variance weighted (IVW) method was used as the primary MR approach, supplemented by MR-Egger regression, weighted median, and weighted/simple mode methods. Heterogeneity tests, funnel plots, and leave-one-out sensitivity analyses were performed to assess the robustness and consistency of the results. Results: MR analysis demonstrated significant positive causal associations between antidepressant use and osteoporosis across two independent datasets (ukb-a-87 and ukb-b-12141), with IVW odds ratios of 1.0035 and 1.0016, respectively. Genetically proxied antidepressant use showed significant causal effects on fractures at all examined sites, with wrist fractures displaying the strongest association (IVW: odds ratio (OR) = 1.0027, p = 0.0041). Effect directions remained consistent across multiple MR methods, with no significant heterogeneity detected. Leave-one-out analyses confirmed no single SNP disproportionately influenced the results. Conclusion: This MR study provides evidence that antidepressant use may directly influence bone metabolism and increase fracture susceptibility, particularly at the wrist. These findings highlight the importance of bone health monitoring in patients receiving antidepressant therapy, especially those at elevated fracture risk. Further mechanistic studies and longitudinal validation are warranted. [ABSTRACT FROM AUTHOR]
	Copyright of Actas Espanolas de Psiquiatria is the property of Maria Lopez-Ibor and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database:	MedicLatina

Description
Abstract:	Background: Antidepressant use has been associated with adverse skeletal outcomes in observational studies, but whether this association is causal remains unclear due to potential confounding factors. This study employed Mendelian randomisation (MR) to systematically evaluate the causal associations between genetically predicted antidepressant use and the risks of osteoporosis and fractures at multiple anatomical sites. Methods: Using publicly available genome-wide association studies (GWAS) datasets, we defined genetically predicted antidepressant use as the exposure and osteoporosis and fractures (spine, leg, and wrist) as outcomes. Genome-wide significant single nucleotide polymorphisms (SNPs) were selected as instrumental variables following dataset harmonisation. The inverse-variance weighted (IVW) method was used as the primary MR approach, supplemented by MR-Egger regression, weighted median, and weighted/simple mode methods. Heterogeneity tests, funnel plots, and leave-one-out sensitivity analyses were performed to assess the robustness and consistency of the results. Results: MR analysis demonstrated significant positive causal associations between antidepressant use and osteoporosis across two independent datasets (ukb-a-87 and ukb-b-12141), with IVW odds ratios of 1.0035 and 1.0016, respectively. Genetically proxied antidepressant use showed significant causal effects on fractures at all examined sites, with wrist fractures displaying the strongest association (IVW: odds ratio (OR) = 1.0027, p = 0.0041). Effect directions remained consistent across multiple MR methods, with no significant heterogeneity detected. Leave-one-out analyses confirmed no single SNP disproportionately influenced the results. Conclusion: This MR study provides evidence that antidepressant use may directly influence bone metabolism and increase fracture susceptibility, particularly at the wrist. These findings highlight the importance of bone health monitoring in patients receiving antidepressant therapy, especially those at elevated fracture risk. Further mechanistic studies and longitudinal validation are warranted. [ABSTRACT FROM AUTHOR]
ISSN:	11399287
DOI:	10.62641/aep.v54i2.2164