Effects of early life stress on bone homeostasis in mice and humans

Abstract

A comprehensive examination of mechanisms linking early life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined on bone microarchitecture (μCT), metabolism (qPCR), and neuronal mediator expression (qPCR) and contrasted with a sample of depressive patients with or without early life stress by analyzing bone mineral density [BMD] (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR expression, higher innervation density in bone and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future prevention strategies should consider early life stress as a risk factor for bone pathologies.Impact StatementSpecific types of stress in early life lead to maladaptive responses in bone metabolism and bone mineral density and hence possibly to bone pathologies.