Fluoxetine Administration During Lactation Impacts the Bone Health of the Dam and the Offspring in Mice

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants during pregnancy and lactation. SSRIs decrease bone mineral density (BMD) across all ages and sexes. Lactation is also characterized by increased bone resorption to mobilize calcium and achieves this via a serotonin-induced hormonal cascade. This serotonin-mediated bone loss is normally restored after weaning but is persistent when an SSRI is administered during the peripartum period. Our lab has previously shown that administration of the SSRI fluoxetine (FLX) during both gestation and lactation results in compromised bone health of the dam, which is characterized by a decreased bone mineral density (BMD). Along with this, we have also shown a decrease in BMD and femoral length in the offspring of the FLX-treated dams at weaning. We hypothesize that FLX usage during lactation only will impact the bone health of the dam as well as the bone health of her offspring due to exposure to FLX via the dam’s milk. Female C57BL/6 mice were randomized to receive the SSRI fluoxetine hydrochloride (20 mg/kg) or saline daily from the beginning of lactation (D0) through the end of lactation (D21), resulting in the following treatments: FLX dams (n=13) and control dams (n=13). The offspring of the treated dams were then harvested at weaning (3 weeks of age). During the peripartal period, the BMD of the dam was monitored via dual x-ray absorptiometry (DEXA). A baseline scan was taken at 6 weeks of age, at the end of pregnancy (E17.5), the beginning of lactation (D2), peak lactation (D10), and at the end of lactation (D21). There was no significant difference in the BMD of the FLX dams compared to the control dams at 6 weeks of age (p=0.9992), E17.5 (p=0.9995), D2 (p>0.9999), or D10 (p>0.9999). However, at D21, the FLX dams had a decreased BMD compared to the control dams (p=0.0493). Along with the decreased BMD of the FLX dams at weaning, there was a significant decrease in femur length in the pups of the FLX dams (p=0.0040). When the pups were separated by sex, the decreased femur length was observed in both the male (p=0.0413) and female (p=0.0047) offspring. These data suggest that fluoxetine use during lactation only results in a decreased BMD of the treated dams, as well as decreased femur length in the exposed offspring in both sexes.