title: In vivo longitudinal micro-CT study of bent long limb bones in rat offspring.
abstract: Micro-computed X-ray tomography (micro-CT) has been reported as a reliable method to assess ex vivo rat and rabbit fetal skeletons in embryo-fetal developmental toxicity studies. Since micro-CT is a non-invasive imaging modality it has the potential for longitudinal, in vivo investigation of postnatal skeletal development. This is the first paper using micro-CT to assess the reversibility of drug-induced bent long bones in a longitudinal study from birth to early adulthood in rat offspring. Analysis of the scans obtained on postnatal Day 0, 7, 21 and 80 showed complete recovery or repair of the bent long limb bones (including the scapula) within the first 3 weeks. When assessing risk the ability to demonstrate recovery is highly advantageous when interpreting such transient skeletal change. In summary, in vivo micro-CT of small laboratory animals can aid in non-clinical safety assessment, particularly for specific mechanistic purposes or to address a particular concern in developmental biology.
authors.affiliation: Preclinical Development & Safety, Janssen R&D, Beerse, Belgium. Electronic address: ldschaep@its.jnj.com.
authors.forename: Luc
authors.initials: L
authors.lastname: De Schaepdrijver
authors.affiliation: Preclinical Development & Safety, Janssen R&D, Beerse, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Delille
authors.affiliation: Biometrics and Reporting, Janssen R&D, Beerse, Belgium.
authors.forename: Helena
authors.initials: H
authors.lastname: Geys
authors.affiliation: Definiens AG, München, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Boehringer-Shahidi
authors.affiliation: Department of Medical Image and Signal Processing, University of Ghent, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Vanhove
mesh_terms: D000375:Aging; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities* / Q000000981:diagnostic imaging*; D005260:Female; D008137:Longitudinal Studies; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D055114:X-Ray Microtomography
keywords: Bent long bones; Micro-computed X-ray tomography (micro-CT); Non-clinical safety assessment; Postnatal skeletal assessment