Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society

Authors

Merle Stein
Florent Elefteriou
Björn Busse
Imke Ak Fiedler
Ronald Young Kwon
Eric Farrell
Mubashir Ahmad
Anita Ignatius
Liam Grover
Liesbet Geris
Jan Tuckermann

Publication Date

8-1-2023

Journal

Journal of Bone and Mineral Research

DOI

10.1002/jbmr.4868

PMID

37314012

PMCID

PMC10962000

PubMedCentral® Posted Date

8-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Animal Experimentation, Reproducibility of Results, Models, Animal, Bone Diseases, Bone and Bones

Abstract

Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last years. Nevertheless, the overall complexity of bone tissue-cross talk and the systemic and local regulation of bone physiology can often only be addressed in entire vertebrates. Powerful genetic methods such as conditional mutagenesis, lineage tracing, and modeling of the diseases enhanced the understanding of the entire skeletal system. In this review endorsed by the European Calcified Tissue Society (ECTS), a working group of investigators from Europe and the US provides an overview of the strengths and limitations of experimental animal models, including rodents, fish, and large animals, as well the potential and short comings of in vitro and in silico technologies in skeletal research. We propose that the proper combination of the right animal model for a specific hypothesis and state-of-the-art in vitro and/or in silico technology is essential to solving remaining important questions in bone research. This is crucial for executing most efficiently the 3R principles to reduce, refine and replace animal experimentation, for enhancing our knowledge of skeletal biology, and for the treatment of bone diseases that affect a large part of society.