(P18-010-24) Effect of Early Life Stress on Skeletal Health

Objectives: This study investigated the impact of chronic early life stress during the postnatal period on skeletal health.

Methods: Timed-pregnant rats were allowed to deliver undisturbed. On postnatal day (PD)2, each litter was randomly assigned to an "impoverished” cage [chronic early life stress (CES)] or a standard cage (STD), and remained undisturbed through PD10. A sample of PD10 pups were sacrificed (n=6/group) and the rest of the litters were returned to standard cages and weaned at PD21. Weaned pups were fed a standard chow diet and were weighed weekly. At PD21 and PD35 (n=12/group), pups were anesthetized and tibia and lumbar vertebra (L4) were collected. Tibial length, tibial and vertebral bone mineral content (BMC) and density (BMD), and tibial cortical bone microarchitecture were assessed. Data were analyzed using 2-way ANOVA with stress exposure and sex as factors followed by post-hoc tests.

Results: CES exposure led to significant (p < 0.05) reductions in tibial length at both PD10 (-8.9%) and PD21 (-5.8%) and tended to be lower at PD35 (p=0.092). Similarly, tibial BMC (-13.3%, p=0.006) and BMD (-6.3%, p=0.042) was lower in the CES group but only at PD21. There was no sex effect on tibial length, BMC and BMD. In the L4 vertebra, significant reductions (p < 0.05) in BMC were observed with CES exposure compared to the STD group at all time points (-33%, -18%, & -9% at PD10, PD21, and PD35, respectively), but only at PD21 (-4.3%) and PD35 (-2.6%) with BMD. Compared to the STD rats, significant sex effects were observed in vertebral BMD with female CES rats having lower BMD (-8.6%) but males are unaffected at PD 21, whereas male CES rats had lower BMD (-13.1%) but females are unaffected at PD35. In terms of cortical bone microarchitecture, tibial cortical thickness and area were significantly higher in the CES group at PD10, lower at PD21, and unaffected at PD35 compared to the STD group. Interestingly, CES caused significant reductions in cortical thickness (-20.2%) and area (-11.4%) in females but not with males at PD21.

Conclusions: Our findings demonstrate the negative effects of CES exposure on bone particularly at PD 21 and highlight the sexual dimorphic impact on skeletal development. As we aim to mitigate the long-term skeletal consequences of early life stress, the contributions of sex and postnatal age must be considered.

Funding Sources: USDA-ARS