Table 2.

Medium and Large Animal Model Advantages, Disadvantages, and Translational Relevance

Animal Model	Advantages	Disadvantages	Cost ($-$$$$)	Most Common Bone Used	Potential Implications of Differences (When Humans are Considered)	References for Further Reading
Rabbit	Bone density is similar to humans; bone contains Haversian systems	Size and shape differs greatly from humans; very fast remodeling compared to humans; differences in composition of the microstructure; vascular longitudinal tissue structure. External fixators are used inconsistently, the tibia is more commonly used than the femur, and bones that carry less weight are frequently used in growth factor studies (such as the ulna)	$$	Femur, Tibia	Faster remodeling may confound the expected speed of healing in the human	16,20,28,29
Canine	Most similar bone density, extractable protein content (such as IGF-1), and ash weight when compared to humans	Regarded as companion animal; trabecular bone may withstand greater compressive forces than human bone due to the increased plexiform bone structure adjacent to the periosteum	$$$	Femur	Mixed microstructure, specifically in the vicinity of the periosteum confers greater mechanical strength	16,21,28,29
Sheep	Most similar body weight when compared to humans; size of bone and weight of animal replicates conditions for human implants and prostheses	High content of plexiform bone conferring greater ability to withstand compression in early life; Haversian remodeling is favored with age; prior to haversian remodeling, sheep bone is comprised mostly of a combination of woven and lamellar bone (primary structure). Ruminant digestive tract affects nutrient cycling and delivery compared to monogastrics; seasonally polyestrous cycle alters bone metabolism	$$$	Tibia	Mixed microstructure, specifically in the vicinity of the periosteum confers greater mechanical strength; Haversian remodeling increases with age in sheep—average age and sex of sheep must be considered when extrapolating to differing populations of human patients. Human bone structure is mostly secondary osteons formed by the replacement of existing bone. It has been suggested the mechanical differences exist since primary bone structure is formed through cartilage mineralization	21,22
Horse	Most similar mechanical loading of the musculoskeletal system when compared to humans	Immediately weight bearing; high cost of anesthesia, housing, and routine care. Studies conducted in small cohorts yield lower statistical power, but confer high scientific evidence; seasonally polyestrous cycle alters bone metabolism	$$$$	Metacarpal IV (MCIV)	Success in the horse likely confers success in the human; if MCIV is used, one must be careful to immediately extrapolate evidence to a persistently weight bearing bone	30