A rapid, high content, in vivo model of glucocorticoid-induced osteoporosis

Abstract

Glucocorticoid-induced osteoporosis (GIOP) is a major clinical problem given the widespread use of steroids and limited efficacy of biphosphonates. Existing animal models of GIOP are both slow and expensive. Hence, there is a need both for adjunctive modelling systems, as well as more efficacious therapies for the treatment of GIOP. We have addressed this issue through the creation of a zebrafish model of GIOP, which can be used for 96-well plate in vivo screening with an assay time of 5 days. The model demonstrates key similarities to human GIOP including a partial response to bisphosphonates. The ability to extract detailed pharmacological data, including concentration-response analyses, enables the screening and ranking of candidate therapeutic compounds. In addition, the zebrafish model is highly relevant for pathway dissection through genetic knockdown and overexpression studies.