Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth.

Abstract:

:Selective serotonin-reuptake inhibitors (SSRIs) antagonize the serotonin (5-hydroxytryptamine) transporter (5-HTT), and are frequently prescribed to children and adolescents to treat depression. However, recent findings of functional serotonergic pathways in bone cells and preliminary clinical evidence demonstrating detrimental effects of SSRIs on bone growth have raised questions regarding the effects of these drugs on the growing skeleton. The current work investigated the impact of 5-HTT inhibition on the skeleton in: 1) mice with a null mutation in the gene encoding for the 5-HTT; and 2) growing mice treated with a SSRI. In both models, 5-HTT inhibition had significant detrimental effects on bone mineral accrual. 5-HTT null mutant mice had a consistent skeletal phenotype of reduced mass, altered architecture, and inferior mechanical properties, whereas bone mineral accrual was impaired in growing mice treated with a SSRI. These phenotypes resulted from a reduction in bone formation without an increase in bone resorption and were not influenced by effects on skeletal mechanosensitivity or serum biochemistries. These findings indicate a role for the 5-HTT in the regulation of bone accrual in the growing skeleton and point to a need for further research into the prescription of SSRIs to children and adolescents.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Warden SJ,Robling AG,Sanders MS,Bliziotes MM,Turner CH

doi

10.1210/en.2004-1259

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

685-93

issue

2

eissn

0013-7227

issn

1945-7170

pii

en.2004-1259

journal_volume

146

pub_type

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