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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}
}
  • The histamine-H/sub 1/ receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a /sup 3/H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H/sub 1/ receptor. Some newer antidepressant drugs, such as zimeldine and nomifensine were devoid of activity while others, such as iprindole and mianserin were very potent. It is concluded that antagonistic effects on the histamine-H/sub 1/ receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs.
  • The natural remodeling and adaptation of skeletal tissues in response to mechanical loading is a classic example of physical regulation in biology. It is largely because it involves forces that do not seem to fit into the familiar schemes of biochemical controls that bone adaptation mechanisms have intrigued us for at least a century. The effect of electromagnetic fields on organisms is another example of this, and the two have become linked in an attempt to explain bone remodeling (Yasuda`s hypothesis). This paper re-examines the roles of endogenous and exogenous electromagnetic fields in the response of bone to mechanical forces.more » A series of experiments is reviewed in which mechanical and electrical stimuli were applied to implants in the medullary canal of rabbit long bones. The results suggest that endogenously generated electrical currents are not required to initiate mechanically stimulated bone formation, but that direct mechanical effects on bone cells is the more likely scenario. Based on this and other evidence from the literature, it is suggested that when exogenous electromagnetic stimuli are applied, bone cells respond by modulating the activity of more primary activators such as hormones, growth factors, cytokines, and mechanical forces. 76 refs., 8 figs.« less
  • The effects of {sup 60}Co gamma irradiation on the initial mechanical properties of the composite bone-patellar tendon-bone unit (CU) and the tendon midsubstance (TM) were studied. Frozen specimens were exposed to either 2 or 3 Mrad of gamma irradiation. Paired frozen specimens served as intraanimal controls. Treatment effects on the CU were assessed using four mechanical parameters. Effects on the TM were assessed using four material parameters measured using an optical surface-strain analysis system. The maximum force and strain energy to maximum force of the composite unit were significantly reduced 27% and 40%, respectively, after 3 Mrad of irradiation (pmore » less than .05). Mechanical properties of the CU were not significantly altered, however, following 2 Mrad of irradiation. Based on individual paired contrasts between treatment and control, significant differences were also found in the material properties of the tendon midsubstance. The maximum stress, maximum strain, and strain energy density to maximum stress were significantly reduced following 3 Mrad, but not 2 Mrad, of irradiation. The results provide important time zero material property data, which will be useful for later anterior cruciate ligament reconstruction studies using irradiated allograft patellar tendons in the goat model and other animal models as well.« less