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Title: Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling

Abstract

The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg{sup -1} day{sup -1} of desipramine, fluoxetine or 10 mg kg{sup -1} day{sup -1} of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (- 6.1%, p < 0.01) and tofisopam higher TbTh (+ 5.0%, p < 0.05) versus placebo. Rolipram and tofisopam treatments induced higher BV/TV than placebo (+ 23.8% and + 18.3% respectively). Desipramine group had significantly higher cortical area (+ 4.8%, p < 0.01) and fluoxetine lower cortical area (- 6.1%, p < 0.01) compared to placebo. The stiffness and Young's modulus were lower in the fluoxetine group (77 {+-} 13 N mm{sup -1},more » 6431 {+-} 1182 MPa) than in placebo (101 {+-} 9 N mm{sup -1}, 8441 {+-} 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (- 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone.« less

Authors:
 [1];  [2];  [3];  [2];  [3];  [2];  [3];  [2];  [3];  [4];  [4]
  1. Inserm U658 CTI, Caracterisation du tissu osseux par imagerie, techniques et applications, Centre Hospitalier regional d'Orleans, Universite d'Orleans, 1, rue porte Madeleine, F-45000 Orleans (France). E-mail: nicolas.bonnet15@wanadoo.fr
  2. Key-obs SA, Parc technologique, Orleans (France)
  3. (France)
  4. Inserm U658 CTI, Caracterisation du tissu osseux par imagerie, techniques et applications, Centre Hospitalier regional d'Orleans, Universite d'Orleans, 1, rue porte Madeleine, F-45000 Orleans (France)
Publication Date:
OSTI Identifier:
20976940
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 221; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.02.005; PII: S0041-008X(07)00076-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANISOTROPY; ENZYME IMMUNOASSAY; FEMUR; FIELD TESTS; FLEXIBILITY; MICE; NITROGEN 13; NORADRENALINE; PARTIAL DIFFERENTIAL EQUATIONS; SEROTONIN; THICKNESS; TRABECULAR BONE; YOUNG MODULUS

Citation Formats

Bonnet, N., Bernard, P., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Beaupied, H, Greenpharma S. A., 3, allee du titane, 45100 Orleans, Bizot, J.C., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Trovero, F., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Courteix, D., and Benhamou, C.L. Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.02.005.
Bonnet, N., Bernard, P., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Beaupied, H, Greenpharma S. A., 3, allee du titane, 45100 Orleans, Bizot, J.C., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Trovero, F., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Courteix, D., & Benhamou, C.L. Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling. United States. doi:10.1016/j.taap.2007.02.005.
Bonnet, N., Bernard, P., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Beaupied, H, Greenpharma S. A., 3, allee du titane, 45100 Orleans, Bizot, J.C., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Trovero, F., Greenpharma S. A., 3, allee du titane, 45100 Orleans, Courteix, D., and Benhamou, C.L. Tue . "Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling". United States. doi:10.1016/j.taap.2007.02.005.
@article{osti_20976940,
title = {Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling},
author = {Bonnet, N. and Bernard, P. and Greenpharma S. A., 3, allee du titane, 45100 Orleans and Beaupied, H and Greenpharma S. A., 3, allee du titane, 45100 Orleans and Bizot, J.C. and Greenpharma S. A., 3, allee du titane, 45100 Orleans and Trovero, F. and Greenpharma S. A., 3, allee du titane, 45100 Orleans and Courteix, D. and Benhamou, C.L.},
abstractNote = {The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg{sup -1} day{sup -1} of desipramine, fluoxetine or 10 mg kg{sup -1} day{sup -1} of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (- 6.1%, p < 0.01) and tofisopam higher TbTh (+ 5.0%, p < 0.05) versus placebo. Rolipram and tofisopam treatments induced higher BV/TV than placebo (+ 23.8% and + 18.3% respectively). Desipramine group had significantly higher cortical area (+ 4.8%, p < 0.01) and fluoxetine lower cortical area (- 6.1%, p < 0.01) compared to placebo. The stiffness and Young's modulus were lower in the fluoxetine group (77 {+-} 13 N mm{sup -1}, 6431 {+-} 1182 MPa) than in placebo (101 {+-} 9 N mm{sup -1}, 8441 {+-} 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (- 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone.},
doi = {10.1016/j.taap.2007.02.005},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 221,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2007},
month = {Tue May 15 00:00:00 EDT 2007}
}