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A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (\u03bcCT), metabolism (qPCR\/ELISA), and neuronal stress mediator expression (qPCR) and compared 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 TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. 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 studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.<\/jats:p>","DOI":"10.3390\/ijms21186634","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:10:09Z","timestamp":1599729009000},"page":"6634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of Early Life Stress on Bone Homeostasis in Mice and Humans"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-4629","authenticated-orcid":false,"given":"Karin","family":"Wuertz-Kozak","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY 14623, USA"},{"name":"Sch\u00f6n Clinic Munich Harlaching, Spine Center, Academic Teaching Hospital and Spine Research Institute of the Paracelsus Medical University Salzburg (AU), 81547 Munich, Germany"},{"name":"Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Roszkowski","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland"},{"name":"Laboratory of Neuroepigenetics, University of Zurich and Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-5421","authenticated-orcid":false,"given":"Elena","family":"Cambria","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4819-2529","authenticated-orcid":false,"given":"Andrea","family":"Block","sequence":"additional","affiliation":[{"name":"Sociology of Health and Physical Activity, University of Potsdam, 14469 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela A.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea","family":"Abele","sequence":"additional","affiliation":[{"name":"Psychoneuroimmunology Laboratory, Department of Psychosomatics and Psychotherapy, University of Gie\u00dfen, 35390 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hitzl","sequence":"additional","affiliation":[{"name":"Research Office (Biostatistics), Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Research Program Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Paracelsus Medical University Salzburg, Department of Ophthalmology and Optometry, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0311-9042","authenticated-orcid":false,"given":"David","family":"Drie\u00dflein","sequence":"additional","affiliation":[{"name":"Statistical Consulting Unit StaBLab, Ludwig-Maximilians-University Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5811-7725","authenticated-orcid":false,"given":"Ralph","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Rapp","sequence":"additional","affiliation":[{"name":"Social and Preventive Medicine, University of Potsdam, 14469 Potsdam, Germany"},{"name":"Department of Health, University of Potsdam, 14469 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle M.","family":"Mansuy","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland"},{"name":"Laboratory of Neuroepigenetics, University of Zurich and Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2423-527X","authenticated-orcid":false,"given":"Eva M. 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