title: Effect of mirtazapine on rat bone tissue after orchidectomy.
abstract: OBJECTIVE
  Our study aimed to investigate the effect of mirtazapine on bone metabolism in the orchidectomized rat model.
  
  
  METHODS
  Rats were divided into three groups. A sham-operated control group (SHAM group) and a control group after orchidectomy (ORX group) received the standard laboratory diet (SLD). An experimental group after orchidectomy (ORX MIRTA group) received SLD enriched with mirtazapine for 12 weeks. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone marker concentrations of osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I, bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 were examined in bone homogenate. The femurs were used for biomechanical testing.
  
  
  RESULTS
  Compared with the control ORX group, we found a lower BMD in the ORX MIRTA group. The differences were statistically significant, although not in the lumbar vertebrae. BMD was lower in the MIRTA group, suggesting a preferential effect on cortical bone. However, although the thickness of the diaphyseal cortical bone was not different, the fragility in the femoral neck area was statistically significantly different between the groups in biomechanical testing. Regarding the bone metabolism markers, there was a significant decrease in OPG and BALP levels, suggesting a reduction in osteoid synthesis.
  
  
  CONCLUSIONS
  The results suggest that prolonged use of mirtazapine may have a negative effect on the synthesis of bone and on its mechanical strength, especially in the femoral neck. Further studies are warranted to establish whether mirtazapine may have a clinically significant adverse effect on bone exclusively in the model of gonadectomized rats, or whether the effect occurs also in the model of gonadally intact animals and in respective human models.
authors: Institute of Clinical Biochemistry and Diagnostics, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors: Sona
authors: S
authors: Fekete
authors: Julius
authors: J
authors: Simko
authors: Martin
authors: M
authors: Mzik
authors: Iva
authors: I
authors: Karesova
authors: Helena
authors: H
authors: Zivna
authors: Ladislava
authors: L
authors: Pavlíková
authors: Vladimir
authors: V
authors: Palicka
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019245:Compressive Strength; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000078785:Mirtazapine; D009919:Orchiectomy; D053244:Osteoprotegerin / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D053244:Osteoprotegerin; C506032:Tnfrsf11b protein, rat; D008803:Mianserin; D000078785:Mirtazapine; D000469:Alkaline Phosphatase