Systematic Search and Modified e-Delphi Consensus for Serum Bone Biomarkers in Humans and Animal Models with SCI: Methodology.

INTRODUCTION

Alterations to bone metabolism deteriorations in bone density and architecture after spinal cord injury (SCI) are complex and multifactorial: mechanical unloading, impaired osteoblast activity, altered hormone levels, and regional blood flow combine to increase lower extremity fracture incidence and mortality. Bone biomarkers are vital to detect disease, identify candidate therapies, monitor therapy effectiveness, and quantify fracture risk.

OBJECTIVES

This study aimed to synthesize available literature on serum and plasma bone biomarkers in both animal and human SCI models and to generate consensus regarding their appropriateness for use across the translational continuum.

METHODS

A systematic search was conducted; 4731 studies were excluded, yielding 125 studies for data extraction. Data were reviewed by an interdisciplinary panel of experts. Through a modified e-Delphi process, consensus statements were iteratively developed regarding the appropriateness of 14 serum bone biomarkers in human and animal models and across the translational continuum.

RESULTS

The consensus process highlighted challenges in interpreting animal and human models, emphasizing the need for methodological rigor and standardized biomarker reporting. Consideration of diurnal variations in biomarkers and model selection (transection vs. clip) underscored the complexity of SCI research. Limitations included defining "adult" rodents and lack of data on sex-related differences in biomarkers and their interpretation, given most human data were obtained from males and animal data from females.

CONCLUSION

The consensus statements provide guidance, address gaps in reporting and interpretation of biomarkers, promote use of standardized protocols and assay kits, and emphasize interdisciplinary approaches to advancing scientific discovery and facilitating knowledge translation.