Application of Histopathology and Bone Histomorphometry for Understanding Test Article-Related Bone Changes and Assessing Potential Bone Liabilities

  • Reinhold G. Erben
  • Jacquelin Jolette
  • Luc Chouinard
  • Rogely Boyce
Chapter
First Online:
Part of the Molecular and Integrative Toxicology book series (MOLECUL)

Abstract

Qualitative histopathology remains the gold standard for hazard identification and safety assessment of potential new therapeutics. Although, in most cases, qualitative histopathology has sufficient sensitivity to detect test article-related effects on bone marrow and growth plates in standard toxicity studies, it may lack the sensitivity to detect effects of test articles on key physiological processes in bone tissue such as bone formation, mineralization, and resorption, which often requires chronic dosing to result in structural changes, such as variation in bone mass, that can be appreciated by qualitative assessment. Bone histomorphometry is an important tool that provides sensitive methods that can detect effects of test articles on bone resorption, formation, mineralization, remodeling rates, and growth before structural changes occur. Bone histomorphometry can be used to understand the cellular mechanisms responsible for test article-related structural changes, detected by histopathology or imaging techniques, or can be used prospectively to address a potential target- or class-related theoretical bone liability. In this chapter we review the methods for embedding, sectioning, staining, and analysis of bone sections and provide some general guidance on approaches for the evaluation of bone and use of histomorphometric analyses applied to preclinical safety assessment.

Keywords

Bone Histomorphometry Bone formation Bone resorption Bone remodeling 
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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Reinhold G. Erben
    • 1
  • Jacquelin Jolette
    • 2
  • Luc Chouinard
    • 2
  • Rogely Boyce
    • 3
  1. 1.Department of Biomedical SciencesUniversity of Veterinary Medicine ViennaViennaAustria
  2. 2.Department of PathologyCharles River Montreal ULCSennevilleCanada
  3. 3.Comparative Biology and Safety SciencesAmgen Inc.Thousand OaksUSA

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