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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function
Biological Psychiatry, Volume 74, No. 1, Year 2013
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Description
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. © 2013 Society of Biological Psychiatry.
Authors & Co-Authors
Berk, Michael
Australia, Geelong
Deakin University
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Orygen Youth Health
Australia, Melbourne
The Florey
Dodd, Seetal M.
Australia, Geelong
Deakin University
Australia, Melbourne
University of Melbourne
Statistics
Citations: 84
Authors: 2
Affiliations: 7
Identifiers
Doi:
10.1016/j.biopsych.2012.11.003
ISSN:
18732402
Research Areas
Cancer
Substance Abuse