Toxicology and applied pharmacology

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

PMID 17383703


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(-1) day(-1) of desipramine, fluoxetine or 10 mg kg(-1) day(-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(-1), 6431+/-1182 MPa) than in placebo (101+/-9 N mm(-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.

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Tofisopam, ≥98% (HPLC), solid