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Specific Considerations for Bone Evaluations for Pediatric Therapeutics

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Bone Toxicology

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

Growth and development of the immature organism can be adversely affected by indirect and direct exposures to xenobiotics. There has been an increase in the requirements for juvenile toxicity testing of pharmaceuticals and biopharmaceuticals since 1998, with regulatory agencies commonly requiring nonclinical studies; particular emphasis is often being placed on evaluations of growth and the development of the skeleton. A number of therapeutic classes have been shown to affect the human pediatric skeleton and various juvenile animal models. A nonclinical approach must be taken for full evaluation of effects on the musculoskeletal system’s development in pharmaceutical testing, because the prolonged times for completion of development in the human precludes a clinical approach. A range of techniques can be used in toxicology studies, including biochemical markers and in vivo imaging that can also be incorporated in clinical trials. These techniques along with routine toxicology endpoints, growth measurements, and ex vivo techniques, such as histomorphometry and biomechanical testing, can be incorporated into juvenile toxicology studies, each of which is designed on a case-by-case basis. Key factors in study design of the nonclinical program are the species, age, dose route, duration of dosing, and the post-dosing development period, and which outcome measures to include.

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  1. Reproductive and Juvenile Toxicology, Charles River Laboratories, 22022 Transcanadienne, Senneville, H9X 3R3, QC, Canada

    Keith Robinson

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  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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Robinson, K. (2017). Specific Considerations for Bone Evaluations for Pediatric Therapeutics. 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_3

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