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.

The Effect of Zonisamide on Rat Bone Mass, Structure, and Metabolism

“…The OPG, as a soluble receptor, binds to the RANKL. RANKL is produced by osteoblastic lineage cells and promotes osteoclast activation, leading to enhanced bone resorption and bone loss [27]. OPG is secreted by osteoblastic cells and prevents the interaction of RANKL with its receptor RANK and subsequent stimulation of osteoclast development [27].…”

“…RANKL is produced by osteoblastic lineage cells and promotes osteoclast activation, leading to enhanced bone resorption and bone loss [27]. OPG is secreted by osteoblastic cells and prevents the interaction of RANKL with its receptor RANK and subsequent stimulation of osteoclast development [27]. BALP is localized in the membranes of osteoblasts, from which it is realized into the serum during their activation [28].…”

Mirtazapine and Depressions

“…In a rat model, there was a suggestion that prolonged use of mirtazapine may have a negative effect on the synthesis of the bone and on its mechanical strength (Fekete et al 2015). To the authors' knowledge, there is no evidence pro or con that mirtazapine accelerates osteoporosis.…”