An Overview of Bone Toxicology

The skeleton is an active and dynamic tissue that interacts with other complex systems such as the endocrine, nervous, and immune systems. During the development of a new therapeutic agent for adult or pediatric populations, the potential for bone-related effects is assessed by a weight of evidence approach consisting of a comprehensive evaluation of data available in the literature and from relevant in vivo and in vitro studies related to the development of the new compound. If concerns are raised based on the clinical indication, pharmacology, pharmacokinetics, or potential direct and/or secondary effects, they need to be correctly addressed in safety assessment nonclinical studies. Depending on the potential expected changes and animal species selected, all or a selection of the specialized bone parameters can be evaluated in standard toxicology studies. Those specialized bone endpoints can include serum or urinary biochemical markers of bone turnover and hormones, in vivo or ex vivo densitometry (dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, microcomputed tomography), radiology, development of the skeleton for juvenile animals, biomechanical strength testing, quantitative static/dynamic histomorphometry, or expanded bone qualitative histopathology.