Interspecies Comparison of Alveolar Bone Biology, Part I: Morphology and Physiology of Pristine Bone

Abstract

Introduction: Few interspecies comparisons of alveolar bone have been documented, and this knowledge gap raises questions about which animal models most accurately represent human dental conditions or responses to surgical interventions. Objectives: The objective of this study was to employ state-of-the-art quantitative metrics to directly assess and compare the structural and functional characteristics of alveolar bone among humans, mini pigs, rats, and mice. Methods: The same anatomic location (i.e., the posterior maxillae) was analyzed in all species via micro–computed tomographic imaging, followed by quantitative analyses, coupled with histology and immunohistochemistry. Bone remodeling was evaluated with alkaline phosphatase activity and tartrate-resistant acid phosphatase staining to identify osteoblast and osteoclast activities. In vivo fluorochrome labeling was used as a means to assess mineral apposition rates. Results: Collectively, these analyses demonstrated that bone volume differed among the species, while bone mineral density was equal. All species showed a similar density of alveolar osteocytes, with a highly conserved pattern of collagen organization. Collagen maturation was equal among mouse, rat, and mini pig. Bone remodeling was a shared feature among the species, with morphologically indistinguishable hemiosteonal appearances, osteocytic perilacunar remodeling, and similar mineral apposition rates in alveolar bone. Conclusions: Our analyses demonstrated equivalencies among the 4 species in a plurality of the biological features of alveolar bone. Despite contradictory results from older studies, we found no evidence for the superiority of pig models over rodent models in representing human bone biology. Knowledge Transfer Statement: Animal models are extensively used to evaluate bone tissue engineering strategies, yet there are few state-of-the-art studies that rigorously compare and quantify the factors influencing selection of a given animal model. Consequently, there is an urgent need to assess preclinical animal models for their predictive value to dental research. Our article addresses this knowledge gap and, in doing so, provides a foundation for more effective standardization among animal models commonly used in dentistry.

Examining the Morphological and Physiological Comparisons of OVX Murine Bone vs. Mini Pigs, Rats, and Humans

“…Across all species, osteocytic lacunae were identified as white voids within the bone matrix and indicated the existence of where previous osteocytes existed. Osteocytes were not visible within the lacunae of human and mini pig (Fig 1A , B) due to difficulties in preserving cell architecture in large animals (Pilawski et al 2020). Nonetheless the morphological similarities are apparent with the presence of Haversian canals and lacunae in all species (Fig.…”

“…1C, D). Most mini pig osteocyte lacunae were empty, which most likely reflected inherent difficulties in preserving cell architecture in large animal models (Pilawski et al 2020). Osteons were clustered together, which was observed in all aniline blue stains (Fig.…”

“…In Pilawski's paper, it was stated that trabecular bone is structurally and physiologically is similar across all species (Pilawski et al, 2020). Pilawski and colleagues also (2020) compared the bone volume of mini pig, mice, and rats found that the bone mineral density was equal.…”

“…There are more well-established protocols and functioning antibodies for mice than mini pigs and rats. For instance, a common human protein RUNX2 and RANKL, two essential regulators in bone physiology, functioned properly in mice but were unable to work in mini pig (Pilawski et al, 2020). This was because mini pig tissue is more difficult to process.…”

“…The stains were submerged in 1% of aniline blue (B8563, sigma) for 1-5 minutes until a dark navy color developed. Slides were then washed in 1% acetic acid (A38-212, Fisher) for 5 minutes and repeated twice for consistency of stain (Pilawski et al, 2020).…”