Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin.
Department of Orthopedics, Brigham and Women's Hospital, Boston, Massachusetts.
Endocrinology. 2018 Aug 1;159(8):2850-2862. doi: 10.1210/en.2018-00279.
Selective serotonin reuptake inhibitors (SSRIs) have been linked to osteopenia and fracture risk; however, their long-term impact on bone health is not well understood. SSRIs are widely prescribed to pregnant and breastfeeding women who might be at particular risk of bone pathology because lactation is associated with considerable maternal bone loss. We used microCT and molecular approaches to test whether the SSRI fluoxetine, administered to C57BL/6 mice from conception through the end of lactation, causes persistent maternal bone loss. We found that peripartum fluoxetine increases serum calcium and reduces circulating markers of bone formation during lactation but does not affect osteoclastic resorption. Peripartum fluoxetine exposure also enhances mammary gland endocrine function during lactation by increasing synthesis of serotonin and PTHrP, a hormone that liberates calcium for milk synthesis and reduces bone mineral volume. Peripartum fluoxetine exposure reduces the trabecular bone volume fraction at 3 months after weaning. These findings raise new questions about the long-term consequences of peripartum SSRI use on maternal health.
选择性 5-羟色胺再摄取抑制剂（SSRIs）与骨量减少和骨折风险有关；然而，它们对骨骼健康的长期影响尚不清楚。SSRIs 被广泛用于孕妇和哺乳期妇女，因为哺乳期与大量母体骨丢失有关，她们可能特别容易出现骨骼病理学。我们使用 microCT 和分子方法来测试在妊娠到哺乳期结束期间给予 C57BL/6 小鼠的 SSRI 氟西汀是否会导致持续的母体骨丢失。我们发现围产期氟西汀会增加血清钙并减少哺乳期的循环骨形成标志物，但不会影响破骨细胞吸收。围产期氟西汀暴露还通过增加血清素和甲状旁腺激素相关肽（PTHrP）的合成来增强哺乳期的乳腺内分泌功能，PTHrP 是一种释放钙用于乳汁合成和减少骨矿物质体积的激素。围产期氟西汀暴露会降低断奶后 3 个月的小梁骨体积分数。这些发现提出了关于围产期使用 SSRIs 对母亲健康的长期后果的新问题。
