## 5 Which Animal Model Is Suitable for Bone Investigation of Osteotomic Effects? A great variety of animal models are present in the scientific literature (Table 2) for investigations of bone effects after osteotomy. As shown in Table 2, there are many similarities and differences regarding bone parameters concerning animal species, and between animals and humans, at the same time. As if it were an aphorism, we can say that the animal model that most resembles human bone features is... the human being! In fact, no animal can perfectly mimic all the static and dynamic human bone characteristics [54]. Given the obvious ethical implications, studies of bone healing or bone damage on humans are very difficult. Nevertheless, investigations can be done by an indirect evaluation--for example, observing the biochemical values in the peri-implant sulcular fluid, the radiologic exams or certain protein (such as Hsp-70) expression in bone specimens collected immediately after an osteotomy [55; 56]. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Animal** & \begin{tabular}{c} **Bone Microscopic and** \\ **Macroscopic Features** \\ \end{tabular}  & \begin{tabular}{c} **Bone Composition** \\ **and Remodeling** \\ \end{tabular}  & **Animal Management** & **Best Type of Study** \\ \hline \multirow{4}{*}{\( \begin{array}{c}\text{Rodents}\\ \text{Rodents}\\ \text{Rodents}\\ \text{Rodents}\\ \text{Rodents}\\ \text{Corntices are thin and}\\ \text{fragile.}\\ \end{array} \)} & \begin{tabular}{c} Limited cortical \\ remodeling and \\ non-Haverasian-type \\ remodeling. Limited \\ secondary osteon \\ formation. Higher \\ bone healing capacity \\ in craniofacial bones. \\ \end{tabular}  & \begin{tabular}{c} Cheap and easily \\ manageable. Rats are \\ more docile and social \\ than mice, although \\ the latter are cheaper \\ to house and maintain. \\ \end{tabular}  & \begin{tabular}{c} Osteoinduction. \\ Cartilage regeneration \\ potential. Bone \\ infection. Extraoral \\ surgical approaches. \\ \end{tabular}  \\  & \begin{tabular}{c} Cortices are fragile and \\ there is less cancellous \\ bone than in humans. \\ Quick achievement of \\ skeletal maturity. \\ Small size. Lack of \\ biomechanical data. \\ Dense Haversian bone. \\ \end{tabular}  & \begin{tabular}{c} Similar bone density to \\ human. Bone \\ metabolism is similar \\ to human, with \\ Haversian-type \\ remodeling, although \\ with a higher rate than \\ humans. \\ \end{tabular}  & \ \begin{tabular}{c} Availability, housing \\ and handling are easy. \\ Cage confinement \\ might worsen their \\ bone healing \\ capability. \\ \end{tabular}  & \begin{tabular}{c} Muscolo-skeletal \\ research. Bone \\ implants. Modeling of \\ vertebral fracture \\ repair. Extraoral \\ surgical approaches. \\ \end{tabular}  \\ \hline \multirow{4}{*}{\(\begin{array}{c}\text{Sheep}\\ \text{Rheep}\\ \text  
However, animal models are invaluable in the study of bone healing (Table 3). The European Commission stressed their central role and \"the three Rs\" have been established as the fundamental pillars of animal experimentation:  
* Reduction: the number of animals involved must be the lowest necessary to achieve scientific evidence;
* Refinement: animals' suffering must be kept to a minimum;
* Replacement: if it is possible, a non-animal-based study is preferred [66; 67]. These rules are imperative for an in vivo animal model. As far as the last point (replacement) is concerned, it has to be said that ex vivo studies (with bone segments provided by commercial slaughter) are suitable to evaluate osteotomic bone damage. Some authors also proposed artificial bone specimens derived from bovine bone due to its thermal conductivity, which is similar to human bone [68; 69]. Altogether, a cost-benefit evaluation of the considered experimentation has to prove the potential for progress in human or animal health over the damage caused to the animals [54]. According to our experience, study-specific criteria must be considered as well.