Imaging techniques enhance musculoskeletal safety and efficacy testing

Abstract

The aim of this work was to establish in vivo imaging procedures to evaluate the effects of drugs on musculoskeletal development in non‐clinical studies with Sprague‐Dawley rats from preweaning to young adult using dual energy x‐ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and radiography. Radiographs were used to measure long bone (femur, tibia) and axial skeleton (L1–L6) length. DXA was used to measure bone area, bone mineral content (BMC) and bone mineral density (BMD) at the femur and spine, and lean/fat mass of the whole body. pQCT was used to measure BMC and BMD of trabecular and cortical bone, bone geometry, and lean/fat area at the proximal tibia. Reproducible DXA and pQCT data were obtained with coefficients of variation <5% for most parameters. Radiographs and pQCT showed increases in bone length, diameter and BMC with age although increases in BMD were variable. Results indicate that radiography, DXA and pQCT provide safe, reproducible and repeated measures of musculoskeletal growth in rats at axial and appendicular sites and will serve as useful tools to enhance safety and efficacy testing in drug development.