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Cited by 122Bone Metabolism and DiseasesBone health and osteoporosis researchBone health and treatments

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Selective Serotonin Reuptake Inhibitors Inhibit Human Osteoclast and Osteoblast Formation and Function

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Hodge, Jason M., Wang, Yiming, Berk, Michael, Collier, Fiona M., Fernandes, Tania J., Constable, Matthew J., Pasco, Julie A., Dodd, Seetal, Nicholson, Geoffrey C., Kennedy, Richard L., Williams, Lana J.·2013·Biological Psychiatry
DOI 10.1016/j.biopsych.2012.11.003
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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 param…

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Metadata

Authors
Hodge, J. M., Wang, Y., Berk, M., Collier, F. M., Fernandes, T. J., Constable, M. J., Pasco, J. A., Dodd, S., Nicholson, G. C., Kennedy, R. L., & Williams, L. J.
Affiliations
  • Deakin University (AU)
  • Guiyang Medical University (CN)
  • Geelong Hospital (AU)
  • The University of Melbourne (AU)
  • The University of Queensland (AU)
Corresponding author
Hodge, Jason M.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2013-07
Volume
74
Issue
1
Pages
32-39
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2012.11.003
OpenAlex
W2026813394
Cited by
122
References
4
Citations by year
2026: 14 · 2025: 11 · 2024: 6 · 2023: 9 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 11 · 2018: 9 · 2017: 14 · 2016: 7 · 2015: 11 · 2014: 7 · 2013: 5
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
selective serotonin reuptake inhibitors, osteoclastogenesis, osteogenic differentiation, bone resorption, bone mineralization, serotonin receptors, tryptophan hydroxylase 1, 5-HT transporter, apoptosis, bone loss, antidepressant side effects, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram
MeSH terms
Antidepressive Agents, Humans, Osteoblasts, Osteoclasts, Receptors, Serotonin, Tryptophan Hydroxylase, Apoptosis, Selective Serotonin Reuptake Inhibitors, Serotonin Plasma Membrane Transport Proteins

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