|Home | About | Journals | Submit | Contact Us | Français|
Animal models have been commonly used for in vivo and in vitro spinal research. However, the extent to which animal models resemble the human spine has not been well known. We conducted a systematic review to compare the morphometric features of vertebrae between human and animal species, so as to give some suggestions on how to choose an appropriate animal model in spine research. A literature search of all English language peer-reviewed publications was conducted using PubMed, OVID, Springer and Elsevier (Science Direct) for the years 1980–2008. Two reviewers extracted data on the anatomy of large animal spines from the identified articles. Each anatomical study of animals had to include at least three vertebral levels. The anatomical data from all animal studies were compared with the existing data of the human spine in the literature. Of the papers retrieved, seven were included in the review. The animals in the studies involved baboon, sheep, porcine, calf and deer. Distinct anatomical differences of vertebrae were found between the human and each large animal spine. In cervical region, spines of the baboon and human are more similar as compared to other animals. In thoracic and lumbar regions, the mean pedicle height of all animals was greater than the human pedicles. There was similar mean pedicle width between animal and the human specimens, except in thoracic segments of sheep. The human spinal canal was wider and deeper in the anteroposterior plane than any of the animals. The mean human vertebral body width and depth were greater than that of the animals except in upper thoracic segments of the deer. However, the mean vertebral body height was lower than that of all animals. This paper provides a comprehensive review to compare vertebrae geometries of experimental animal models to the human vertebrae, and will help for choosing animal model in vivo and in vitro spine research. When the animal selected for spine research, the structural similarities and differences found in the animal studies must be kept in mind.
Various large animals, such as pig, calf, sheep, baboon, deer, goat and dog spines as models have been used for in vivo and in vitro spinal research [1, 7, 11, 12, 17, 18, 21, 22]. In vitro models consisting of cadaveric spine specimens are useful in providing basic understanding of the functioning of the spine. In vivo models provide the means to model living phenomena, such as fusion, development of disc degeneration, instability and adaptive responses in segments adjacent to spinal instrumentation. Basically, human specimens are more suitable for these models than are animal specimens whenever anatomy, size (for instrumentation) and kinematics are important. However, there are some disadvantages in using the human model. One problem is the difficulty in obtaining fresh human specimens, especially from the younger population. Another problem with the use of human specimens is the large variation in geometry and mechanical properties due to differences in age, sex, bone quality and disc and bone degenerative changes. These disadvantages of human specimens force a search for alternative animal models; and, most in vivo and in vitro experiments have been performed in animal spines, which are more easily available and have more uniform geometrical and mechanical properties. To mimic the clinical situation, an appropriate animal should have similar characteristic anatomical dimensions of spine to those in humans as possible.
Up til now, basic studies about the anatomical suitability for several large animal spines exist [2–6, 8–10, 20, 23, 24]. However, in nearly all these studies, only single animal was used to do the comparative anatomical study with the human spine. Therefore, a systematic review is needed to analyze the differences and similarities of vertebrae between human and all large animals studied, so as to determine the extent to which animal models more resemble the human spine. Thus, the purpose of this study is to summarize the differences and similarities of anatomy between human and animal models, and give some suggestions on how to choose a better animal model in vivo and in vitro experiment.
PubMed, OVID, Springer and Elsevier (Science Direct) were searched using the keywords: animal(s), human, spine (spinal), lumbar, thoracic, cervical, anatomy, anatomic, anatomical, morphometry, sheep, pig (swine, porcine), calf (bovine), baboon, deer, goat (ovine) and dog (canine). The search was limited to studies on spine anatomy of large animals, published in English and in the period from January 1980 up to August 2008. References of retrieved articles and of relevant overview articles were checked to identify additional studies.
Two reviewers independently checked eligible articles on title, keywords and abstract. A consensus meeting was used to discuss disagreements. Reports on studies were included if they met the following inclusion criteria: (1) large animal used in spine research: sheep, pig, calf, baboon, deer, goat and dog, (2) anatomical study of cervical, or thoracic or lumbar spine, (3) at least three vertebral levels were measured in the study. Two reviewers then extracted data from all the included papers relating to the anatomy of animal spines. We compare the spinal anatomy of these animal models with that of human from seven anatomical parameters: vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), spinal canal width (SCW), spinal canal depth (SCD), pedicle width (PW) and pedicle depth (Table 1, Fig. 1). The comparative human parameters were taken from published literature, for various regions of the spine—cervical (Panjabi et al. ), thoracic (Panjabi et al. ) and lumbar (Panjabi et al. ) were recorded.
Among the 544 papers found, 510 papers were not considered, because they do not include any relevant anatomical information on animal spine. Furthermore, 37 papers were discarded because they did not meet the inclusion criteria mentioned above. In total, seven eligible studies were reviewed for further analysis. There was one report on baboon cervical spine , two papers on sheep spine [8, 23], two papers on porcine spine [2, 6], one paper on calf spine  and one paper on deer spine . These studies are summarized in Table 2. Comparisons of each anatomical parameter of human [13–15], baboon , sheep , porcine [2, 6], calf  and deer  are shown in Figs. 2, 3, 4, 5, 6, 7, 8, 9, 10 11 and Tables 3, 4, 5, 6 7, respectively. The sheep, porcine and deer have more than 12 thoracic vertebrae, and the human has only 12 thoracic vertebrae, therefore, we just compared the parameters from T1 to T12 between them.
In cervical region, the baboon spine is nearly half of human, and the increase trend of spine is similar to that in humans. The sheep spine is larger than human, particularly in VBH, and the trend is opposite to that in humans. In thoracic and lumbar regions, the mean human VBW and VBD are greater than that of the animals, except in upper thoracic segments of the deer; the mean VBH is lower than that of all animals (Tables 3, 4, 5; Figs. 2, 3, 4, 5, 6, 7).
The human spinal canal is wider and deeper in the anteroposterior plane than any of the animals. The human is similar to the all animal model in increase trend of SCW, but the increase trend of SCD is opposite, except the sheep, deer and porcine lumbar spine (Table 6; Figs. 8, 9).
Basic spine research and preclinical testing of new surgical methods often involve animal experiments because most tests cannot be carried out on humans or the availability of human specimens is limited. Currently, large animal models, such as sheep, pig, calf, baboon, deer, goat and dog spines have been used to substitute for human spine [1, 7, 11, 12, 17, 18, 21, 22]. Before using animal models, it is necessary to study how the parameters of interest differ between species to be aware of the limitations of any particular animal model and to ensure conclusions reached are applicable to human. The current review shows although qualitatively, the anatomy of the spine of these species is similar to that of human, the sizes of some parameters differ considerably, including greater VBHs, lower VBW and VBD, smaller spinal canal and greater PH. Therefore, the ideal animal model for human spine does not exist. The differences between human and quadruped spines may affect the consequences for the interpretation of experimental results. These differences and similarities should be kept in mind, when choosing an animal model for study of human spinal conditions and treatments.
Although based on such comparative data of these animal models, it is difficult to interpret, whether a certain species is most suitable to be used as the human spine, we can choose an appropriate animal model based on the factors such as, anatomy, availability and cost, etc. Kandziora et al.  concluded that the sheep cervical spine is suitable as a model for cervical spine research. An analysis of existing data in the present study shows that only considering VBH, the baboon cervical spine is the best model to substitute for human, while the VBH of sheep cervical spine is significantly greater than that of human spine . In terms of VBW, the trend of the sheep cervical spine is the opposite to that in humans from C2 to C7. Although the baboon cervical spine is smaller than human’s, the VBW trend is similar to human. Therefore, in cervical region, spines of the baboon and human are more similar as compared to sheep, indicating the baboon may be a better substitution for human cervical spine in anatomy, which might be their closely shared gene homology . In lower thoracic and upper lumbar regions, deer may be used as an alternative to human specimens, if the differences are taken into consideration. Sheep spine may be a useful model for experiments related to the gross structure of the thoracic or lumbar spine, with certain limitations for the cervical spine . The most suitable for human spine of porcine is from T6 to T10, and the lumbar spine of porcine is an alternative to human specimens. The calf is an alternative to human thoracic and lumbar specimens, if the differences are taken into consideration. When compared with human spine, another relevant issue of using animal models is difference in size, which is important for the used implants and screw lengths. The VBH is larger for most animals, which results in a larger corpectomy size. For the PH, most animal pedicles are larger than human, indicating a human pedicle screw can be used in animal models. Animals seem to be small for human cage sizes due to lower VBW and VBD. Only if we know how the parameters of interest differ between animal and human spine, experimental studies involving interbody cages, and screw–rod systems could be sized appropriately to provide meaningful results.
Although each porcine, calf, deer or sheep could be a choice of experimental animal for in vivo and in vitro experimental studies according to anatomical studies, several factors such as biomechanical property, availability, costs, breeding and growth also should be considered. The animals selected for spine in vivo research must be of an appropriate size both at the beginning and at the end of the experiment. Therefore, mature sheep model could be chosen for in vitro experimental use. Pig and calf generally are not to be considered for in vivo experimentation is that they grow too rapidly, high cost and not easy to handle. Calf model (age 6–8 weeks) in the present review study include open growth plates, and may lead to oversize vertebrae. Mature porcine (age 18–24 months) may avoid these limitations. Therefore, in stability biomechanical testing, both calf and porcine models could be selected for thoracic and lumbar spine research. However, when used as a traumatic model, the presence of open growth plates in immature calf spine specimens, which may affect the results of biomechanical experiment, have to be considered. The deer spine specimens could be an alternative to calf and porcine for human thoracic and lumbar spine, but it has the disadvantage of difficult availability and higher cost.
In all included papers, fresh specimens were evaluated anatomically, and parameters were measured using digitized caliper or hand-held micrometer. However, some limitations of the current study have to be noted. First, this study has not included bone mineralization and biomechanical properties of the specimens that may influence the choice of experimental specimens. Theoretical considerations show that the spine of the quadruped animal is mainly loaded along its long axis, just like the human spine . However the animals have higher vertebral bone densities, thus, indicating that axial compression stress is higher than in humans . Moreover, significant differences have been identified in flexibility testing between animal and human cadaveric specimens . All differences of these biomechanical properties may affect the animal models as a substitute for human spine. Secondly, the present study was aimed solely at identifying published peer-reviewed English literature, so that publication bias cannot be entirely ruled out. Thirdly, the present study excluded the paper on the morphometry of a single vertebra from large animal models [5, 10], which may lost some information. However, we believe data from more than a single vertebra is necessary, because spinal instrumentation and implant testing are commonly at least three vertebral levels, and more important is to show the anatomical trend of the vertebrae. Finally, the present study did not make an anatomical comparison of all the segments of the animal spines to that of the humans, because of the different measurement conditions. Therefore, the anatomy of the goat and canine spines and the porcine and calf cervical spines need to be studied in the near future.
This study gives us a clear view of similarities and differences of vertebrae geometries between common experimental animal and human spines. This will be useful to choose animal model in vivo and in vitro spine research; also, when a certain animal is selected for spine research, the structural similarities and differences found in the animal model studies must be kept in mind.
This work is supported by a Grant from the China National Nature Fund (Grant no. 30700843).
Sun-Ren Sheng, Email: moc.621@03328nernusgnehs.
Hua-Zi Xu, Phone: +86-577-88829799, Fax: +86-577-88879123, Email: moc.361@ux-enips.