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脊髓损伤的人类和动物模型中血清骨生物标志物的系统检索与改良电子德尔菲共识法:方法学

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

作者信息

Tsang Philemon, Cleland Matthew, Wiest Matheus, Cowley Kristine C, Newton Emily, Patsakos Eleni, Ponzano Matteo, Giangregorio Lora, Aliabadi Saina, Armstrong Katrina, Fouad Karim, Magnuson David, Craven B Catharine

机构信息

KITE Research Institute, Toronto Rehabilitation Institute - University Health Network, Toronto, ON, Canada.

Institute of Health Policy Management and Evaluation, University of Toronto, Toronto ON, Canada.

出版信息

Top Spinal Cord Inj Rehabil. 2025 Spring;31(2):13-28. doi: 10.46292/sci24-00042. Epub 2025 Jun 19.

DOI:10.46292/sci24-00042
PMID:40585013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12199597/
Abstract

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.

摘要

引言

脊髓损伤(SCI)后骨代谢改变、骨密度和结构恶化是复杂且多因素的:机械卸载、成骨细胞活性受损、激素水平改变以及局部血流变化共同导致下肢骨折发生率和死亡率增加。骨生物标志物对于疾病检测、确定候选治疗方法、监测治疗效果以及量化骨折风险至关重要。

目的

本研究旨在综合动物和人类SCI模型中血清和血浆骨生物标志物的现有文献,并就是否适合在整个转化过程中使用形成共识。

方法

进行了系统检索;排除4731项研究,得到125项用于数据提取的研究。数据由一个跨学科专家小组进行审查。通过改良的电子德尔菲法,就14种血清骨生物标志物在人类和动物模型以及整个转化过程中的适用性反复制定共识声明。

结果

共识过程突出了在解释动物和人类模型方面的挑战,强调了方法严谨性和标准化生物标志物报告的必要性。对生物标志物昼夜变化和模型选择(横断与夹闭)的考虑凸显了SCI研究的复杂性。局限性包括定义“成年”啮齿动物以及缺乏关于生物标志物性别差异及其解释的数据,因为大多数人类数据来自男性,而动物数据来自女性。

结论

共识声明提供了指导,解决了生物标志物报告和解释方面的差距,促进了标准化方案和检测试剂盒的使用,并强调了跨学科方法以推进科学发现和促进知识转化。

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本文引用的文献

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Rehabilitation: Neurogenic Bone Loss after Spinal Cord Injury.康复:脊髓损伤后的神经源性骨质流失
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Inflammaging and Bone Loss in a Rat Model of Spinal Cord Injury.脊髓损伤大鼠模型中的炎症老化与骨丢失。
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Biomarkers from Secondary Complications in Spinal Cord Injury.脊髓损伤继发并发症的生物标志物
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Spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury in skeletally mature rats.骨骼成熟大鼠小梁骨和皮质骨对完全性脊髓损伤的时空反应
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The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury.运动和基于活动的物理疗法对脊髓损伤后骨骼的影响。
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Bone loss after severe spinal cord injury coincides with reduced bone formation and precedes bone blood flow deficits.严重脊髓损伤后发生的骨丢失与成骨减少同时发生,并先于骨血流不足。
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