A groundbreaking study conducted at Ulm University and its Medical Center has shed light on the molecular mechanisms behind how psychological trauma and severe stress can impede the healing of bone fractures.
Researchers from Ulm University, along with scientists from Canada and Japan, collaborated to reveal that specific immune cells respond to stress by producing an enzyme. This enzyme, in turn, triggers the release of stress hormones that hinder bone growth by interfering with the conversion of cartilage cells into bone cells. The study’s implications are particularly relevant for emergency rescue workers, victims of natural disasters, and violence, as their high-stress experiences can have lasting effects on their bone healing processes in the event of serious injuries.
Professor Stefan Reber, who leads the Laboratory for Molecular Psychosomatics at the Department of Psychosomatic Medicine and Psychotherapy in Ulm, and Professor Melanie Haffner-Luntzer from the Institute of Orthopaedic Research and Biomechanics coordinated the research. Their findings were published in the prestigious journal Nature Communications.
The immune cells responsible for this stress response are known as neutrophil granulocytes, a type of white blood cell that belongs to the innate immune system. Under severe mental stress, these immune cells produce an enzyme called tyrosine hydroxylase (TH), which induces the local production and release of specific stress hormones called catecholamines, including adrenaline, noradrenaline, and dopamine, at the site of the fracture hematoma. These stress hormones negatively affect the transition of cartilage cells to bone cells, thereby slowing down the healing process of bones.
Dr. Miriam Tschaffon-Müller from the Institute of Orthopaedic Research and Biomechanics, along with Elena Kempter, a doctoral researcher at Professor Reber’s lab, served as the two first authors of the study. They demonstrated the stress-induced mechanism at the molecular genetic level by using knockout mice with suppressed TH expression and blocked adrenoceptors, which showed no inhibition of bone healing under stress.
In the clinical part of the research, the team collaborated with the Department of Orthopaedic Trauma, Hand, Plastic, and Reconstruction Surgery, as well as the Department of Psychosomatic Medicine and Psychotherapy to study patients with ankle fractures. The study revealed that patients with high psychological stress, trauma, or depression displayed elevated levels of tyrosine hydroxylase (TH) in their fracture hematoma, leading to impaired fracture healing. Surprisingly, the subjective rating of the patients’ mental stress load and their pain perception played a crucial role in these measurable effects.
The study’s findings have significant implications for clinical practice, suggesting that considering a patient’s stress or trauma history could be crucial when treating fractures and other major injuries. In some cases, using beta blockers to mitigate the negative impact of stress hormones on bone healing may be advisable.
In conclusion, this research provides valuable insights into the connection between psychological stress and bone healing, and it offers potential avenues for improving patient outcomes in orthopedic care.