Summary <p>Post-traumatic bone loss occurs after major injuries like traumatic brain injury (TBI), spinal cord injury (SCI), burns, and fractures, yet its systemic effects remain underexplored. This review summarizes clinical and preclinical evidence, highlighting key mechanisms and their impact on fracture risk.</p> Introduction <p>Traumatic injuries can lead to systemic bone loss. While spinal cord injury (SCI)–related bone loss is well studied, the effects of TBI, burns, and fractures on bone metabolism remain less clear. This review examines post-traumatic bone loss across different injuries to guide future research, preventive, and treatment strategies.</p> Methods <p>We conducted a systematic review according to PRISMA guidelines. PubMed, Web of Science, Scopus, and Science Direct were searched up to January 2025 using MeSH terms and keyword combinations related to traumatic injuries and bone loss. Studies were screened based on pre-defined inclusion and exclusion criteria, and relevant clinical and preclinical data were extracted and synthesized.</p> Results <p>The review included a total of 165 studies, including 5 clinical and 9 preclinical TBI studies, 73 clinical and 39 preclinical SCI studies, 16 clinical and 6 preclinical burn studies, and 10 clinical and 45 preclinical fracture studies. SCI can cause up to 50% BMD reduction within weeks, while burns lead to up to 8% BMD loss within two months, with osteoporosis affecting 10 to 50% of patients. TBI is linked to increased osteopenia and osteoporosis, and fractures result in BMD changes of 5 to 28% in the injured limb, along with a higher risk of subsequent fractures on either side. Preclinical studies confirmed impaired bone quality, increased resorption, and decreased formation across injury types. The potential mechanisms contributing to post-traumatic bone loss include mechanical unloading with increased sclerostin signaling, systemic inflammation driving osteoclastogenesis, nervous system dysregulation changing neuroosteogenic interaction, nutritional and metabolic imbalances, and hormonal disturbances involving parathyroid hormone, growth hormone, and cortisol.</p> Conclusion <p>Post-traumatic bone loss presents a distinct etiology, resulting from an interaction of mechanical, inflammatory, neural, nutritional, and hormonal factors. Recognizing these mechanisms is essential for developing targeted interventions to prevent bone deterioration, reduce fracture risk, and improve long-term patient outcomes after trauma.</p> Graphical Abstract <p>Overview of mechanisms of post-traumatic bone loss. Mechanisms driving bone turnover imbalance following traumatic injuries, including TBI, TSCI, burns, and fractures. Contributing factors such as mechanical unloading, post-traumatic inflammation, disruptions in vitamin D, calcium, and PTH regulation, along with metabolic, endocrine, and nervous system dysregulation, result in reduced bone formation and increased bone resorption. These changes lead to bone loss, hindering recovery and compromising overall bone health. Created with BioRender (BioRender.com). <a href="https://BioRender.com/l4">https://BioRender.com/l4</a></p> <p></p>

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Beyond the initial impact: a systematic review of post-traumatic bone loss and its mechanisms

  • Adibeh Rahmani,
  • Ulrike Weichelt,
  • Denise Jahn,
  • Ellen Otto,
  • Arne Kienzle,
  • Svilen Angelov,
  • Vanessa Hubertus,
  • Jennifer Shue,
  • Alexander P. Hughes,
  • Georg N. Duda,
  • Serafeim Tsitsilonis,
  • Matthias Pumberger,
  • Paul Köhli

摘要

Summary

Post-traumatic bone loss occurs after major injuries like traumatic brain injury (TBI), spinal cord injury (SCI), burns, and fractures, yet its systemic effects remain underexplored. This review summarizes clinical and preclinical evidence, highlighting key mechanisms and their impact on fracture risk.

Introduction

Traumatic injuries can lead to systemic bone loss. While spinal cord injury (SCI)–related bone loss is well studied, the effects of TBI, burns, and fractures on bone metabolism remain less clear. This review examines post-traumatic bone loss across different injuries to guide future research, preventive, and treatment strategies.

Methods

We conducted a systematic review according to PRISMA guidelines. PubMed, Web of Science, Scopus, and Science Direct were searched up to January 2025 using MeSH terms and keyword combinations related to traumatic injuries and bone loss. Studies were screened based on pre-defined inclusion and exclusion criteria, and relevant clinical and preclinical data were extracted and synthesized.

Results

The review included a total of 165 studies, including 5 clinical and 9 preclinical TBI studies, 73 clinical and 39 preclinical SCI studies, 16 clinical and 6 preclinical burn studies, and 10 clinical and 45 preclinical fracture studies. SCI can cause up to 50% BMD reduction within weeks, while burns lead to up to 8% BMD loss within two months, with osteoporosis affecting 10 to 50% of patients. TBI is linked to increased osteopenia and osteoporosis, and fractures result in BMD changes of 5 to 28% in the injured limb, along with a higher risk of subsequent fractures on either side. Preclinical studies confirmed impaired bone quality, increased resorption, and decreased formation across injury types. The potential mechanisms contributing to post-traumatic bone loss include mechanical unloading with increased sclerostin signaling, systemic inflammation driving osteoclastogenesis, nervous system dysregulation changing neuroosteogenic interaction, nutritional and metabolic imbalances, and hormonal disturbances involving parathyroid hormone, growth hormone, and cortisol.

Conclusion

Post-traumatic bone loss presents a distinct etiology, resulting from an interaction of mechanical, inflammatory, neural, nutritional, and hormonal factors. Recognizing these mechanisms is essential for developing targeted interventions to prevent bone deterioration, reduce fracture risk, and improve long-term patient outcomes after trauma.

Graphical Abstract

Overview of mechanisms of post-traumatic bone loss. Mechanisms driving bone turnover imbalance following traumatic injuries, including TBI, TSCI, burns, and fractures. Contributing factors such as mechanical unloading, post-traumatic inflammation, disruptions in vitamin D, calcium, and PTH regulation, along with metabolic, endocrine, and nervous system dysregulation, result in reduced bone formation and increased bone resorption. These changes lead to bone loss, hindering recovery and compromising overall bone health. Created with BioRender (BioRender.com). https://BioRender.com/l4