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

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Bone Toxicology

Part of the book series: Molecular and Integrative Toxicology ((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.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria

    Reinhold G. Erben MD, DVM

  2. Department of Pathology, Charles River Montreal ULC, 22022 Transcanadienne, Senneville, QC, Canada, H9X 3R3

    Jacquelin Jolette DVM, MSc, Dip ACVP & Luc Chouinard DVM, DES, DACVP

  3. Comparative Biology and Safety Sciences, Amgen Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA

    Rogely Boyce DVM, PhD, DACVP

Authors
  1. Reinhold G. Erben MD, DVM
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  2. Jacquelin Jolette DVM, MSc, Dip ACVP
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  3. Luc Chouinard DVM, DES, DACVP
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  4. Rogely Boyce DVM, PhD, DACVP
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Corresponding author

Correspondence to Reinhold G. Erben MD, DVM .

Editor information

Editors and Affiliations

  1. Montreal, Québec, Canada

    Susan Y. Smith

  2. Charles River Preclinical Services, Senneville, Québec, Canada

    Aurore Varela

  3. Charles River Preclinical Services, Senneville, Québec, Canada

    Rana Samadfam

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Erben, R.G., Jolette, J., Chouinard, L., Boyce, R. (2017). Application of Histopathology and Bone Histomorphometry for Understanding Test Article-Related Bone Changes and Assessing Potential Bone Liabilities. In: Smith, S., Varela, A., Samadfam, R. (eds) Bone Toxicology. Molecular and Integrative Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-56192-9_8

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