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This version published online on November 11, 2004
Endocrinology, doi:10.1210/en.2004-1259
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Submitted on September 23, 2004
Accepted on November 1, 2004

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

Stuart J. Warden*, Alexander G. Robling, Megan S. Sanders, Michael M. Bliziotes, and Charles H. Turner

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Portland Veteran Affairs Medical Center, Portland, OR, USA; Oregon Health and Science University, Portland OR USA; Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, IN, USA

* To whom correspondence should be addressed. E-mail: stwarden{at}iupui.edu.

Selective serotonin-reuptake inhibitors (SSRIs) antagonize the serotonin 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 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, while 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.
Key words: bone metabolism • neurotransmitter • osteoporosis • prozac • SSRI




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