Serotonin (5-hydroxytryptamine) transporter inhibition causes bone loss in adult mice independently of estrogen deficiency
Serotonin (5-hydroxytryptamine) transporter inhibition causes bone loss in adult mice independently of estrogen deficiency
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DOI：
10.1097/gme.0b013e318173566b
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发表时间：
2008-11-01
影响因子：
2.7
通讯作者：
Turner, Charles H.
中科院分区：
文献类型：
--
作者：
Warden, Stuart J.;Nelson, Ian R.;Turner, Charles H.
目的：选择性血清素再摄取抑制剂（SSRI）通过拮抗血清素（5-羟色胺）转运蛋白（5-HTT）来治疗抑郁症。鉴于骨骼中存在功能性血清素通路，并且有证据表明 SSRIs 对绝经后骨骼变化具有不利影响，这些药物也可能对骨骼产生影响。本研究旨在探讨 SSRI（盐酸氟西汀）油对成年小鼠雌激素缺乏相关的骨骼变化的影响。 设计：成年雌性 Swiss-Webster 小鼠接受卵巢切除术 (OVX) 或假 OVX，每天使用盐酸氟西汀（5 或 20 毫克/千克）或载体溶液（对照）治疗，持续 4 周。在基线和干预 4 周后对后肢面积和胫骨体积骨矿物质密度进行体内评估。随后取出股骨和腰椎，并离体评估骨矿物质密度、骨小梁结构和更新。结果：体内和离体骨骼测量发现 OVX（雌激素缺乏）和 5-HTT 抑制之间没有相互作用，表明这些干预措施的骨骼效应是独立的。 5-HTT 抑制会对骨骼产生有害影响，氟西汀治疗组的骨矿物质密度降低并改变小梁结构。这些变化是由于骨形成减少和骨吸收增加造成的。结论：这些数据表明，常用的 SSRI 对成人骨骼有负面影响，与雌激素缺乏无关。这一发现支持了临床数据，证明 SSRI 的使用与绝经后骨质流失加速有关，并强调需要进一步研究 SSRI 的骨骼影响。
Objective: Selective serotonin reuptake inhibitors (SSRIs) treat depression by antagonizing the serotonin (5-hydroxytryptamine) transporter (5-HTT). These drugs may also have skeletal effects given the presence of functional serotonergic pathways in bone and evidence demonstrating detrimental effects of SSRIs on postmenopausal bone changes. This Study aimed to explore the influence of an SSRI (fluoxetine hydrochloride) oil the bone changes associated with estrogen deficiency in adult mice.Design: Adult, female, Swiss-Webster mice underwent ovariectomy (OVX) or sham OVX and were treated daily for 4 weeks with either fluoxetine hydrochloride (5 or 20 mg/kg) or a vehicle solution (control). In vivo assessments of hindlimb areal and tibial volumetric bone mineral density were performed at baseline and after 4 weeks of intervention. Femurs and lumbar vertebrae were subsequently removed and assessed ex vivo for bone mineral density and trabecular bone architecture and turnover.Results: In vivo and ex vivo skeletal measures found no interactions between OVX (estrogen deficiency) and 5-HTT inhibition, indicating that the skeletal effects of these interventions were independent. 5-HTT inhibition had detrimental skeletal effects, with the fluoxetine-treated groups having reduced bone mineral density and altered trabecular architecture. These changes resulted from both a decrease in bone formation and increase in bone resorption.Conclusions: These data indicate that a commonly prescribed SSRI has a negative influence on the adult skeleton, independent of estrogen deficiency. This finding Supports clinical data demonstrating SSRI use to be associated with accelerated bone loss after menopause and highlights a need for further research into the skeletal effects of SSRIs.