Negative effect of serotonin-norepinephrine reuptake inhibitor therapy on rat bone tissue after orchidectomy.
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.
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address: sona.fekete@fnhk.cz.
Sona
S
Fekete
Department of Neurology, Charles University in Prague, Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic.
Julius
J
Simko
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Martin
M
Mzik
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Iva
I
Karesova
Radioisotope Laboratories and Vivarium, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Helena
H
Zivna
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Pavel
P
Zivny
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Ladislava
L
Pavliková
Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Vladimir
V
Palicka
D015502:Absorptiometry, Photon; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D024042:Collagen Type I / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D005819:Genetic Markers; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D009919:Orchiectomy; D053244:Osteoprotegerin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D017208:Rats, Wistar; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000633:toxicity*; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D000069470:Venlafaxine Hydrochloride / Q000633:toxicity*
D015415:Biomarkers; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D005819:Genetic Markers; D053244:Osteoprotegerin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; C486031:Sost protein, rat; C506032:Tnfrsf11b protein, rat; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000069470:Venlafaxine Hydrochloride; D000469:Alkaline Phosphatase
BALP; Bone mineral density; CTX-I; SNRI; Venlafaxine