Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use

Abstract

Background: In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation) in concert with the AO Research Institute (ARI), and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research.

Methods: The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows:

Results & conclusion: Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS) according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1) Intelligent study designs to receive appropriate answers; 2) Minimal complication rates (5 to max. 10%); 3) Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA) audit of protocols in GLP studies; 4) Sufficient details for materials and methods applied; 5) Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences); 6) Post-operative management with emphasis on analgesia and follow-up examinations; 7) Study protocols to satisfy criteria established for a "justified animal study"; 8) Surgical expertise to conduct surgery on animals; 9) Pilot studies as a critical part of model validation and powering of the definitive study design; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards.

Figure 1

Suspension system for sheep: the net is adapted from horse rescue principles (Fürst A, et al.) and was custom made for sheep as a prophylactic measure to avoid refractures of their limbs after (experimental) osteosynthesis. A) The net prevents animals to lie down while still being able to rest and move freely within the stall. The net is loosely wrapped around the rump, the soft belts around the neck and hind limbs of the sheep still allowing them to urinate and defecate without problems. For this reason only female sheep should be utilized for experiments requiring the suspension system. B) The net and belts are bundled above the animal and fixed to a hook on the ceiling with a special device and pulley system that allows free rotation for 360°. A special feeder is used with an extension below where the sheep can rest their heads while sleeping and hanging in the nets. Since social contact is important, animals are never kept alone but always have another sheep as a neighbour.