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.

• MeSH
• alfa blokátory krev   farmakokinetika   farmakologie   MeSH
• alkalická fosfatasa metabolismus   MeSH
• antidepresiva tricyklická krev   farmakokinetika   farmakologie   MeSH
• biomechanika MeSH
• kosti a kostní tkáň účinky léků   metabolismus   fyziologie   MeSH
• kostní denzita účinky léků   MeSH
• mianserin analogy a deriváty   krev   farmakokinetika   farmakologie   MeSH
• mirtazapin MeSH
• orchiektomie MeSH
• osteoprotegerin metabolismus   MeSH
• pevnost v tlaku MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa blokátory MeSH
• alkalická fosfatasa MeSH
• antidepresiva tricyklická MeSH
• mianserin MeSH
• mirtazapin MeSH
• osteoprotegerin MeSH
• Tnfrsf11b protein, rat MeSH Prohlížeč

Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.

• Klíčová slova
• BALP, Bone mineral density, CTX-I, SNRI, Venlafaxine,
• MeSH
• absorpční fotometrie MeSH
• alkalická fosfatasa metabolismus   MeSH
• bederní obratle diagnostické zobrazování   účinky léků   MeSH
• biologické markery metabolismus   MeSH
• biomechanika MeSH
• femur diagnostické zobrazování   účinky léků   MeSH
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu toxicita   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   účinky záření   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetické proteiny metabolismus   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• lidé MeSH
• orchiektomie * MeSH
• osteoprotegerin metabolismus   MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy metabolismus   MeSH
• potkani Wistar MeSH
• prokolagen metabolismus   MeSH
• remodelace kosti účinky léků   MeSH
• tibie účinky léků   metabolismus   MeSH
• venlafaxin hydrochlorid toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• biologické markery MeSH
• Bmp2 protein, rat MeSH Prohlížeč
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
• kolagen typu I MeSH
• kostní morfogenetické proteiny MeSH
• kostní morfogenetický protein 2 MeSH
• osteoprotegerin MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH
• Sost protein, rat MeSH Prohlížeč
• Tnfrsf11b protein, rat MeSH Prohlížeč
• venlafaxin hydrochlorid MeSH