Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function

Hodge, Jason M., Wang, Yiming, Williams, Michael, Collier, Fiona M., Fernandes, Tania J., Constable, Matthew J., Pasco, Julie A., Dodd, Seetal, Nicholson, GeoffreyC., Kennedy, Richard L. and Williams, Lana J. (2013) Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function. Biological Psychiatry, 74 1: 32-39. doi:10.1016/j.biopsych.2012.11.003

Author Hodge, Jason M.
Wang, Yiming
Williams, Michael
Collier, Fiona M.
Fernandes, Tania J.
Constable, Matthew J.
Pasco, Julie A.
Dodd, Seetal
Nicholson, GeoffreyC.
Kennedy, Richard L.
Williams, Lana J.
Title Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2013-07
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2012.11.003
Open Access Status
Volume 74
Issue 1
Start page 32
End page 39
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2013
Language eng
Formatted abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants and one of the most commonly used medications. There is growing concern that SSRIs, which sequester in bone marrow at higher concentrations than brain or blood, increase bone fragility and fracture risk. However, their mechanism of action on human osteoclasts (OC) and osteoblasts (OB) differentiation remains unclear.
Methods: Expression of serotonin receptors (5-HTR), transporter (5-HTT), and tryptophan hydroxylase 1 (TPH1) was assessed in human OC (precursors and mature) and OB (nonmineralizing and mineralizing) by polymerase chain reaction. OC formation and resorption was measured in the presence of 5 SSRIs. OBs cultured with SSRIs for 28 days were assessed for alkaline phosphatase (ALP) and bone mineralization. Cell viability and apoptosis were determined by annexin V flow cytometry.
Results: OCs and OB expressed TPH1, 5-HTT, and 5-HTR1B. The 5-HTR2A was expressed only in OB, whereas 5-HTR2B expression increased from precursor to mature OC. All SSRIs (except citalopram) dose-dependently inhibited OC formation and resorption between 1 μmol/L and 10 μmol/L; order of potency: sertraline>fluoxetine>paroxetine>fluvoxamine>citalopram. Similarly, SSRIs (except citalopram) inhibited ALP and bone mineralization by OB but only at 30 μmol/L. Apoptosis was induced by SSRIs in OC and OB in an identical pattern to inhibitory effects. Serotonin treatment had no effect on either OC or OB parameters.
Conclusions: These data demonstrate that SSRIs differentially inhibit bone cell function via apoptosis. This may explain the mechanisms of bone loss with chronic use and aid clinical choices.
Keyword Antidepressant
Selective serotonin reuptake inhibitor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes © 2012 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
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Created: Mon, 15 Apr 2013, 16:56:42 EST by Erin Bowly on behalf of Rural Clinical School