Gerstenfeld Louis C, Wronski Thomas J, Hollinger Jeffrey O, Einhorn Thomas A
Department of Orthopaedic Surgery, Orthopaedic Research Laboratory, Boston University Medical Center, Boston, Massachusetts 02118, USA.
J Bone Miner Res. 2005 Oct;20(10):1715-22. doi: 10.1359/JBMR.050702. Epub 2005 Jul 5.
Standardized methods for the histomorphometric assessment of bone are essential features of most studies of metabolic bone diseases and their treatments. These methodologies were developed to assess coupled remodeling, focusing primarily on osteoblasts and osteoclasts, the anabolic and catabolic rates of these cells, and structural features of mature bone. Research studies on bone healing and the development of new therapeutic approaches for the enhancement of bone repair also require a comprehensive understanding of the basic cellular and tissue level mechanisms that underlie these processes. However, the histological methods developed for metabolic bone disease studies are not completely suitable for studies of bone repair because they are based on assumptions that there is little variation in tissue composition within a sample of bone and not generally designed to quantify other types of tissues, such as cartilage, that contribute to bone healing. These techniques also do not provide tissue-based structural measurements that are relatable to the specific types of biomechanical and radiographic structural assessments that are used to determine rates of bone healing. These deficiencies in current histological approaches therefore point to the need to establish standardized criteria for the histomorphometric assessments that are specifically adapted for the study of bone repair in models of fracture healing and bone regeneration. In this Perspective, we outline what we believe to be the specific structural, tissue. and cellular aspects that need to be addressed to establish these standardized criteria for the histomorphometric assessment of bone repair. We present the specific technical considerations that need to be addressed to appropriately sample repair tissues to obtain statistically meaningful results and suggest specific procedures and definitions of nomenclatures for the application of this technology to bone repair. Finally, we present how aspects of histomorphometric measurements of bone repair can be related to biomechanical and radiographic imaging properties that functionally define rates of bone healing, and thus, how these tools can be used to provide corroborating data.
骨组织形态计量学评估的标准化方法是大多数代谢性骨疾病及其治疗研究的基本特征。这些方法学是为评估耦合重塑而开发的，主要关注成骨细胞和破骨细胞、这些细胞的合成代谢和分解代谢率以及成熟骨结构特征。关于骨愈合的研究以及开发促进骨修复的新治疗方法也需要全面了解这些过程背后的基本细胞和组织水平机制。然而，为代谢性骨疾病研究开发的组织学方法并不完全适用于骨修复研究，因为它们基于这样的假设：骨样本内的组织组成变化很小，并且通常不是为了量化其他有助于骨愈合的组织类型（如软骨）而设计的。这些技术也没有提供与用于确定骨愈合率的特定类型生物力学和放射学结构评估相关的基于组织的结构测量。因此，当前组织学方法的这些不足表明需要为组织形态计量学评估建立标准化标准，这些标准应专门适用于骨折愈合和骨再生模型中的骨修复研究。在本观点中，我们概述了我们认为在为骨修复的组织形态计量学评估建立这些标准化标准时需要解决的特定结构、组织和细胞方面的问题。我们提出了为适当采集修复组织以获得具有统计学意义的结果而需要解决的具体技术考虑因素，并建议了将该技术应用于骨修复的具体程序和术语定义。最后，我们展示了骨修复组织形态计量学测量的各个方面如何与在功能上定义骨愈合率的生物力学和放射影像学特性相关，从而展示了这些工具如何用于提供确证数据。
