Mental Health and Bone Regeneration

Mental trauma can be caused by single or multiple traumatic events during lifetime or by long-lasting psychological and/or psychosocial stress. Especially chronic stress is a major burden of modern life and poses a clear risk factor for a plethora of somatic and psychiatric disorders. A role of the immune system in the development of stress-associated somatic and psychiatric disorders is very likely, given that: i) both stress-associated somatic and mental disorders go along with a dysregulated and over-reacting immune system; ii) risk factors for mental disorders promote immune hyper-reactivity to psychosocial stress and iii) chronic psychosocial stress induces chronic low-grade inflammation in healthy individuals. Because bone and especially bone regeneration are highly influenced by osteoimmunological mechanisms, we hypothesized that chronic stress and mental health problems might be associated with disturbances in bone homeostasis and healing. We investigated that in various preclinical models for chronic psychosocial stress during pregnancy, childhood or during adulthood. We found that stress during pregnancy induced an osteopenic bone phenotype in male offspring only, while early life stress induced a mild osteocatabolic phenotype in female mice only. In contrast, chronic adult stress did not affect the bones of female mice, while male mice displayed reduced long bone length and disturbed endochondral ossification. Because endochondral ossification is also important for secondary fracture healing, we investigated the effects of chronic adult stress on bone regeneration in male mice. Indeed, we found a disturbed inflammatory response towards fracture with increased number of catecholamine-producing neutrophils in the fracture hematoma. This led to reduced endochondral ossification and thereby contributing to disturbed bone regeneration. In conclusion, we could show that chronic stress during various phases of life might affect bone health in a sex-dependent manner and might also interfere with bone regeneration. Molecular mechanisms might be a dysregulated immune system and thereby osteoimmunological crosstalks.