Project 6

Effects of repeated psychosocial traumatisation/chronic psychoscial stress on bone metabolism

Although a strong association between psychiatric and somatic disorders is generally accepted, little is known regarding the interrelation between mental and skeletal health. While depressive disorders were shown to be strongly associated with osteoporosis and increased fracture risk, evidence from post-traumatic stress disorder (PTSD) patients is less consistent. Given that the CSC paradigm induces a behavioural, physiological and immunological phenotype closely related to what is known from PTSD patients, we hold a stress model in hand allowing us to investigate the possible mechanisms underlying disturbance of bone metaolism in PTSD patients.

Therefore, in collaboration with the group of Prof. Anita Ignatius (Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm), here mainly with Dr. Melanie Haffner-Luntzer, we are investigating in male mice whether and how chronic psychosocial stress induced by the chronic subordinate colony housing (CSC) model influences bone metabolism and fracture healing. Besides typical physiological stress consequences, like increased adrenal weight, decreased thymus weight and increased anxiety-related behaviour, our findings indicate a disturbed long bone development as well as compromized fracture healing in chronically stressed compared to unstressed control mice, which are both likely to be at least in part mediated by disturbance of endochondral ossification processes (Förtsch et al., 2017 DMM; Haffner-Luntzer et al., 2019 PNAS). These findings offer possibilities for clinical translation in patients suffering from PTSD and fracture.

The value and clinical relevance of this interdisciplinary project has been acknowledged with the "ORS Travel Award 2018" from the "Deutsche Gesellschaft für Orthopädie und Unfallchirurgie  (DGOU, Germany Scoiety for Orthopaedics and Trauma)" and the "ISFR Award 2019" from the "Orthopaedic Research Society (ORS) for Dr. Melanie Haffner-Luntzer (Institute of Orthopedic Research and Biomechanics, Prof. A. Ignatius, University Medical Center Ulm).

Funding: German Research Foundation, Project B06 within the CRC 1149, INST 40/599-1, PIs  Prof. Dr. Stefan Reber Ulm and Dr. Melanie Haffner-Luntzer;  Gender Equality Funding of Dr. Melanie Haffner-Luntzer provided by the DFG-funded CRC1149; University intern budget of SOR; previously funded by the Innovation fond of the medical faculty of the Ulm University.