Microscopic Evaluations of Bone in Equine and Muroid Models

Abstract

The use of advanced imaging techniques has greatly improved orthopedic research and education. Histology of bone is a method of evaluating bone morphology, bony cells, and bone remodeling in two-dimensions, while micro-computed tomography (microCT) is a three-dimensional analysis of bone morphology. Combined, these methods assist in providing a comprehensive analysis of bone. In this dissertation, these techniques were utilized to answer questions currently outstanding in veterinary medicine: the effect of bisphosphonates on equine bone, and variation in murine tarsal anatomy. Bisphosphonates are drugs that reduce osteoclast-mediated bone resorption and have recently been approved for the use in horses. Despite prolific clinical use, there has been little evidence of their effect on bone in horses. Therefore, the goal of these studies was to determine the impact of bisphosphonates on bone in normal, young horses. This was accomplished by evaluating bone biopsies taken before and 60 days after a single bisphosphonate administration. Biopsies were analyzed using microCT and histomorphometry. We found that the bisphosphonates studied have minimal to no effect on bone morphology and remodeling, and therefore conclude that these drugs do not negatively impact bone, and have no effect after 60 days. Mice are the most commonly utilized animal model for orthopedic research, and knowledge of normal anatomy is critical to identify pathologies secondary to disease. We found conflicting evidence regarding the tarsal anatomy in the mouse. While normal tarsal variation exists in other species, this has not been documented in the mouse. Therefore, the purpose of this study was to characterize the tarsal anatomy of the mouse. MicroCT data from muroid tarsi were collected, and representative tarsi were evaluated by histology. Fusion of the central and tarsal bone III was present in all laboratory mice evaluated, but was not present in the laboratory rat or wild white-footed mouse. This fusion was confirmed via histology; however, hyaline cartilage was present, surrounded by mature trabecular bone indicating a joint remnant despite the fused state of the bones. We conclude that in certain laboratory mouse strains, the central and tarsal bone III are fused into a single bone.