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Use of the dog and cat in experimental maxillofacial surgery
Chapter
10
Use of the dog and cat in experimental maxillofacial surgery M. Anthony Pogrel & Xudong Wang The use of dogs and cats as animal models for human research has a long history which is often arbitrary, and not always based on science. In fact, the use of animal models in general has a somewhat checkered history, both scientifically and emotionally. At the present time, attempts are being made to move away from live animal models as much as possible, and to move to the use of simulation, biomimetics and tissue cultures, etc. Where animal models need to be used, an attempt has been made to move to smaller animals, including rodents, for studies where size is not an important part of the study. However, instances still remain where it is required to use an animal that is large enough to render simulation as realistic as possible to obtain realistic results. Primates have always been felt to be the most realistic animal models for human research, but costs have increased such as to make them unusable for anything but the largest studies. Dogs and cats have been used extensively, but their use is decreasing because of noted differences in size, biology and physiology between dogs and cats and humans, and also cost issues and psychological issues related to the use of animals which are also domestic pets. Animals such as pigs,1–3 sheep4–6 and goats7–9 are becoming more frequently used as animal models, in part because of the larger and more realistic size, biological similarities to humans,3,10–12 and also because there may be less emotion attached to their use.
DOGS In the maxillofacial region, dogs have a long history of use as an animal model, usually for hard tissue (bone and teeth) research, but also for soft tissue studies. The rationale often given for the use of dogs is that their size makes them large enough for realistic surgical procedures to be carried out. In fact, studies have shown that in some respects they are about the smallest animal that can be used for some realistic studies of human maxillofacial procedures. Their teeth are also of similar size and pulpal pattern to those of humans, and they have similar periodontal ligament attachments as human teeth.13,14 The bony architecture of the mandible and maxilla is also similar to humans with Haversian systems (unlike rats), and they are the © 2012 Elsevier Ltd DOI: 10.1016/B978-0-7020-4618-6.00010-5
smallest animals with a similar pattern of bone remodeling to humans.15,16 Growth, remodeling, structural and chemical properties, and mineralization of bone is similar to that of humans. Age-related bony changes are also similar to humans.17 They are cooperative animals, and there is often no need for general anesthesia for relatively simple procedures such as obtaining photographs, making measurements, and even procedures such as cleaning teeth, or adjusting dental appliances or braces. This can be a considerable advantage in some studies.
Bone turnover It is generally agreed that the bone turnover time in dogs is faster than that in humans, and that fractures heal more rapidly in dogs than humans.18 However the process of fracture healing in dogs is essentially similar to that in humans.18 Bone turnover time is normally expressed as sigma, which is one complete bone turnover cycle, including both a resorptive phase and an appositional phase.19–23 This time for the beagle is felt to be two to three times that of a human,23–28 though other studies have suggested it is around 1.5 times as great.29 Variations are possible for a number of reasons. It is known that variations occur within the same species of dogs, and certainly there are variations between species of dogs. There is also a variation depending on age. It must be remembered that most animal experiments involving dogs are carried out on fairly young dogs, usually for financial reasons, whilst equivalent human operations may be carried out on more mature humans. Bone turnover is obviously going to be more rapid in younger animals. There are also variations in bone turnover time for cortical bone versus medullary bone, and this should be taken into account when studies are compared. Studies carried out on animals may not therefore be directly transferred to humans,15 or even to clinical veterinary practice. The critical size defect has been established for the canine cranium at around 20 mm, and for the canine mandible it is at 15 mm if the periosteum is removed and 50 mm if it is intact.30,31 A critical size defect is one which, if created, will not heal spontaneously. Critical size defects are used for research on bone grafting and reconstruction techniques involving a variety of osteoconductive and osteoinductive agents.32,33
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Facial growth As we move away from the use of primates in maxillofacial studies, dogs have been examined for their use in a number of studies of facial growth. Losken et al. determined that the mandibular growth pattern of the dog shows similar relative percentage changes in different regions in juvenile through adult stages, as do those of the human being, and suggested that dogs may be an acceptable, inexpensive alternative to primates in certain maxillofacial growth situations.34 Similarly, dogs have also been studied for their ability to be used as spontaneous animal models of human disease. For example, many dogs suffer from maxillary brachygnathism as a natural phenomenon. In fact, it is even a requirement in the official standards established for certain breeds, including the English toy spaniel, French bulldog, English bulldog and boxers.35 Brachycephaly in dogs is a regional manifestation of achondroplasia, and occurs naturally in some breeds.35 Hereditary multiple exostosis has also been recognized to occur in several breeds including the West Highland white terrier, cairn and Boston terriers, Great Danes and Labrador retrievers.36 Data suggest that these animals may make suitable models for investigation of the etiology and treatment of infantile cortical hyperostosis in human infants.36,37 Dogs have also been used in studies involving orthognathic surgery and tooth viability.13
Periodontal disease The beagle suffers naturally from periodontal disease and periodontal degeneration, and has been widely used in studies of periodontal disease and in evaluations of a variety of surgical and nonsurgical treatments of periodontal disease.14,38 More recently, the beagle has been used in studies utilizing membrane technology as a method of treating periodontal disease in humans.39,40 Postoperative infection rates are extremely low in dogs, and this may also need to be taken into account in studies of healing following certain procedures. Single genomic beagle models have recently been developed which should lead to more standardization of research data. Soft tissue studies on dogs have included grafting materials for vestibuloplasty (increasing the amount of gingiva for dentures to rest on).41
Implants Dogs have also been used extensively in studies on various aspects of osteointegrated dental implants for tooth replacement, including osteointegration time, degree of osteointegration, effects of early and late loading, and the effects of orthodontic forces.42–50 Some of these studies have been combined with the use of growth factors.39,43 Although these studies have been valuable, it does need to be borne in mind that the bone turnover time is more rapid in dogs than in humans, and thus the studies may not be directly transferrable to the human situation or even to clinical veterinary practice. Despite the possible dissimilarities between bone healing in dogs and humans, the canine model has become popular for investigating the management of periodontal disease, both around natural teeth
and around implants, and the concept of a barrier membrane to encourage new bone growth. This has led to the concept of a criticalsize supra-alveolar periodontal defect and the related critical-size supra-alveolar peri-implant defect in the canine animal model. In the beagle dog model, this critical size defect is around 5 mm all around a natural tooth or implant.44,45
Distraction Dogs have also been used to look at various aspects of distraction osteogenesis, which is a more recent technique for slowly moving facial bones by means of gradual distraction following an initial osteotomy.51–54 Again, many of the parameters utilized in humans have been established from animal research utilizing dogs. However, it needs to be emphasized that the bone turnover rate is faster in dogs than in humans.
CATS The use of cats as experimental animals in oral and maxillofacial surgery is not found as frequently as dogs, possibly because they are smaller animals and therefore may not be quite as realistic a model, and also because they are not as cooperative as dogs, and therefore may need anesthetizing more often for procedures to be carried out. Nevertheless, cats have been used for a variety of hard and soft tissue studies. They have been widely used for orthodontic studies involving tooth movement because the crown to root ratio and periodontal ligaments are similar to that of humans and therefore it is felt that the tooth movement obtained orthodontically on a cat may be realistically transferred to the human.55–58 Studies have shown that the cat may be the most realistic nonprimate model for nasal growth studies to simulate results in humans.59 In the soft tissues, studies involving the temporalis muscle have been carried out on cats, and this appears to be related to the fact that cats have a prominent temporalis muscle which is particularly amenable to surgical procedures.60–62
Nerve studies The cat has also been used for studies on the lingual and inferior alveolar nerves, with particular reference to the response of this nerve to injury, and spontaneous and surgically induced regeneration, and also the value of a number of nerve growth factors which may aid reconstruction and regrowth of the branches of the trigeminal nerve.63–70 The rationale for utilizing the cat for these studies appears to be that there is a long history of its use, and the cat appears to lend itself to carrying out single neuron studies on the branches of the trigeminal nerve, which can be extremely valuable in a number of physiological studies. Injury to the inferior alveolar and lingual nerves occurs in humans as a result of trauma and a variety of surgical procedures including wisdom tooth removal.71,72 Loss of sensation, or dysesthesia, causes considerable morbidity and hence the necessity for a reliable animal model.73
REFERENCES 1. Terheyden H, Knak C, Jepsen S, et al. Mandibular reconstruction with a prefabricated vascularized bone graft using recombinant human osteogenic protein-1: an experimental study in miniature pigs.
94
Part I: Prefabrication. Int J Oral Maxillofac Surg 2001;30:373–9. 2. Henkel KO, Ma L, Lenz JH, et al. Closure of vertical alveolar bone defects with guided horizontal distraction osteogenesis:
an experimental study in pigs and first clinical results. J Craniomaxillofac Surg 2001;29:249–53. 3. Troulis MJ, Glowacki J, Perrott DH, et al. Effects of latency and rate on bone
Use of the dog and cat in experimental maxillofacial surgery formation in a porcine mandibular distraction model. J Oral Maxillofac Surg 2000;58:507–13; discussion 514. 4. Uckan S, Schwimmer A, Kummer F, et al. Effect of the angle of the screw on the stability of the mandibular sagittal split ramus osteotomy: a study in sheep mandibles. Br J Oral Maxillofac Surg 2001;39:266–8. 5. Matsuura H, Miyamoto H, Ishimaru JI, et al. Costochondral grafts in reconstruction of the temporomandibular joint after condylectomy: an experimental study in sheep. Br J Oral Maxillofac Surg 2001;39:189–95. 6. Gaggl A, Schultes G, Regauer S, et al. Healing process after alveolar ridge distraction in sheep. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 90:420–9. 7. Hu J, Tang Z, Wang D, et al. Changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction. J Oral Maxillofac Surg 2001;59:1041–5; discussion 1046. 8. Denissen H, Montanari C, Martinetti R, et al. Alveolar bone response to submerged bisphosphonate-complexed hydroxyapatite implants. J Periodontol 2000;71:279–86. 9. Bravetti P, Membre H, Marchal L, et al. Histologic changes in the sinus membrane after maxillary sinus augmentation in goats. J Oral Maxillofac Surg 1998;56:1170–6; discussion 1177. 10. Fukuta K, Har-Shai Y, Collares MV, et al. The viability of revascularized calvarial bone graft in a pig model. Ann Plast Surg 1992;29:136–42. 11. Gerard D, Gotcher JE, McKay H, et al. Is RAP responsible for higher bone activity around implants? J Dent Res 1992;71: 1466. 12. Rose EH, Vistnes LM, Ksander GA. The panniculus carnosus in the domestic pig. Plast Reconstr Surg 1977;59:94–7. 13. Zisser G, Gattinger B. Histologic investigation of pulpal changes following maxillary and mandibular alveolar osteotomies in the dog. J Oral Maxillofac Surg 1982;40:332–9. 14. Haney JM, Zimmerman GJ, Wikesjo UM. Periodontal repair in dogs: evaluation of the natural disease model. J Clin Periodontol 1995;22:208–13. 15. Nunamaker DM. Experimental models of fracture repair. Clin Orthop Relat Res 1998:S56–65. 16. Meller Y, Kestenbaum RS, Mozes M, et al. Mineral and endocrine metabolism during fracture healing in dogs. Clin Orthop Relat Res 1984:289–95. 17. Martin RK, Albright JP, Jee WS, et al. Bone loss in the beagle tibia: influence of age, weight, and sex. Calcif Tissue Int 1981; 33:233–8. 18. Frost HM. Tetracycline-based histological analysis of bone remodeling. Calcif Tissue Res 1969;3:211–37.
19. Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part I of IV parts: mechanisms of calcium transfer between blood and bone and their cellular basis: morphological and kinetic approaches to bone turnover. Metabolism 1976;25:809–44. 20. Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone diseases. II. PTH and bone cells: bone turnover and plasma calcium regulation. Metabolism 1976;25:909–55. 21. Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part III of IV parts; PTH and osteoblasts, the relationship between bone turnover and bone loss, and the state of the bones in primary hyperparathyroidism. Metabolism 1976;25:1033–69. 22. Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part IV of IV parts: The state of the bones in uremic hyperaparathyroidism – the mechanisms of skeletal resistance to PTH in renal failure and pseudohypoparathyroidism and the role of PTH in osteoporosis, osteopetrosis, and osteofluorosis. Metabolism 1976;25:1157–88. 23. Kimmel DB, Jee WS. A quantitative histologic study of bone turnover in young adult beagles. Anat Rec 1982;203: 31–45. 24. High WB, Capen CC, Black HE. Histomorphometric evaluation of the effects of intermittent 1,25-dihydroxycholecalciferol administration on cortical bone remodeling in adult dogs. Am J Pathol 1981;104:41–9. 25. Anderson C, Danylchuk KD. Appositional bone formation rates in the Beagle. Am J Vet Res 1979;40:907–10. 26. Anderson C, Danylchuk KD. Age-related variations in cortical bone-remodeling measurements in male Beagles 10 to 26 months of age. Am J Vet Res 1979; 40:869–72. 27. Snow GR, Karambolova KK, Anderson C. Bone remodeling in the lumbar vertebrae of young adult beagles. Am J Vet Res 1986;47:1275–7. 28. Snow GR, Anderson C. The effects of continuous estradiol therapy on cortical bone remodeling activity in the spayed beagle. Calcif Tissue Int 1985;37: 437–40. 29. Kim SG, Kim YU, Park JC, et al. Effects of presurgical and post-surgical irradiation on the healing process of Medpor in dogs. Int J Oral Maxillofac Surg 2001;30: 438–42.
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30. Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 1986:299–308. 31. Huh JY, Choi BH, Kim BY, et al. Critical size defect in the canine mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:296–301. 32. Sherris DA, Murakami CS, Larrabee WF Jr, et al. Mandibular reconstruction with transforming growth factor-beta1. Laryngoscope 1998;108:368–72. 33. Yudell RM, Block MS. Bone gap healing in the dog using recombinant human bone morphogenetic protein-2. J Oral Maxillofac Surg 2000;58:761–6. 34. Losken A, Mooney MP, Siegel MI. A comparative study of mandibular growth patterns in seven animal models. J Oral Maxillofac Surg 1992;50:490–5. 35. Andrews E, Ward B, Altman N. Spontaneous animal models of human disease. Vol II. New York: Academic Press; 1979. p. 222. 36. Andrews E, Ward B, Altman N. Spontaneous animal models of human disease. Vol II. New York: Academic Press; 1979. p. 223. 37. Thornburg LP. Infantile cortical hyperostosis (Caffey-Silverman syndrome). Animal model: craniomandibular osteopathy in the canine. Am J Pathol 1979;95:575–8. 38. Giannobile WV, Finkelman RD, Lynch SE. Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I. J Periodontol 1994;65:1158–68. 39. Ruskin JD, Hardwick R, Buser D, et al. Alveolar ridge repair in a canine model using rhTGF-beta 1 with barrier membranes. Clin Oral Implants Res 2000;11:107–15. 40. Dongieux JW, Block MS, Morris G, et al. The effect of different membranes on onlay bone graft success in the dog mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:145–51. 41. Rosner TM, Stern K, Doku HC. Autogenous dermal grafting vestibuloplasty in dogs. J Oral Maxillofac Surg 1982;40:9–12. 42. Gotfredsen K, Berglundh T, Lindhe J. Bone reactions adjacent to titanium implants subjected to static load of different duration. A study in the dog (III). Clin Oral Implants Res 2001;12:552–8. 43. Becker W, Lynch SE, Lekholm U, et al. A comparison of ePTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freeze-dried bone in promoting bone formation around immediate extraction socket implants. J Periodontol 1992;63: 929–40. 44. Wikesjo UM, Nilveus R. Periodontal repair in dogs. Healing patterns in large
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circumferential periodontal defects. J Clin Periodontol 1991;18:49–59. 45. Lee J, Decker JF, Polimeni G, et al. Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs. J Clin Periodontol 2010;37:582–90. 46. Block MS, Almerico B, Crawford C, et al. Bone response to functioning implants in dog mandibular alveolar ridges augmented with distraction osteogenesis. Int J Oral Maxillofac Implants 1998;13:342–51. 47. Block MS, Gardiner D, Almerico B, et al. Loaded hydroxylapatite-coated implants and uncoated titanium-threaded implants in distracted dog alveolar ridges. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89:676–85. 48. Redlich M, Reichenberg E, Harari D, et al. The effect of mechanical force on mRNA levels of collagenase, collagen type I, and tissue inhibitors of metalloproteinases in gingivae of dogs. J Dent Res 2001;80: 2080–4. 49. Ohmae M, Saito S, Morohashi T, et al. A clinical and histological evaluation of titanium mini-implants as anchors for orthodontic intrusion in the beagle dog. Am J Orthod Dentofacial Orthop 2001;119:489–97. 50. Liou EJ, Figueroa AA, Polley JW. Rapid orthodontic tooth movement into newly distracted bone after mandibular distraction osteogenesis in a canine model. Am J Orthod Dentofacial Orthop 2000;117:391–8. 51. Cho BC, Seo MS, Baik BS. Distraction osteogenesis after membranous bone onlay grafting in a dog model. J Oral Maxillofac Surg 2001;59:1025–33. 52. Hollis BJ, Block MS, Gardiner D, et al. An experimental study of mandibular arch widening in the dog using distraction osteogenesis. J Oral Maxillofac Surg 1998;56:330–8. 53. Block MS, Chang A, Crawford C. Mandibular alveolar ridge augmentation
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in the dog using distraction osteogenesis. J Oral Maxillofac Surg 1996;54:309–14. 54. Klotch DW, Ganey TM, Slater-Haase A, et al. Assessment of bone formation during osteoneogenesis: a canine model. Otolaryngol Head Neck Surg 1995;112: 291–302. 55. Guajardo G, Okamoto Y, Gogen H, et al. Immunohistochemical localization of epidermal growth factor in cat paradental tissues during tooth movement. Am J Orthod Dentofacial Orthop 2000;118: 210–19. 56. Burrow SJ, Sammon PJ, Tuncay OC. Effects of diazepam on orthodontic tooth movement and alveolar bone cAMP levels in cats. Am J Orthod Dentofacial Orthop 1986;90:102–5. 57. Long A, Loescher AR, Robinson PP. A histological study on the effect of different periods of orthodontic force on the innervation and dimensions of the cat periodontal ligament. Arch Oral Biol 1996;41:799–808. 58. Long A, Loescher AR, Robinson PP. A quantitative study on the myelinated fiber innervation of the periodontal ligament of cat canine teeth. J Dent Res 1995;74: 1310–17. 59. Losken A, Mooney MP, Siegel MI. Comparative cephalometric study of nasal cavity growth patterns in seven animal models. Cleft Palate Craniofac J 1994;31: 17–23. 60. Cheung LK. Microvascular network of the healing surface over the temporalis flap in maxillary reconstruction. Int J Oral Maxillofac Surg 1999;28:469–74. 61. Cheung LK. The epithelialization process in the healing temporalis myofascial flap in oral reconstruction. Int J Oral Maxillofac Surg 1997;26:303–9. 62. Cheung LK. An animal model for maxillary reconstruction using a temporalis muscle flap. J Oral Maxillofac Surg 1996;54:1439–45. 63. Holland GR, Robinson PP, Smith KG, et al. A quantitative morphological study
of the recovery of cat lingual nerves after transection or crushing. J Anat 1996; 188(Pt 2):289–97. 64. Smith KG, Robinson PP. An experimental study on the recovery of the lingual nerve after injury with or without repair. Int J Oral Maxillofac Surg 1995;24: 372–9. 65. Smith KG, Robinson PP. The effect of delayed nerve repair on the properties of regenerated fibres in the chorda tympani. Brain Res 1995;691:142–52. 66. Smith KG, Robinson PP. An experimental study of three methods of lingual nerve defect repair. J Oral Maxillofac Surg 1995;53:1052–62. 67. Smith KG, Robinson PP. An experimental study of lingual nerve repair using epineurial sutures or entubulation. Br J Oral Maxillofac Surg 1995;33: 211–19. 68. Smith KG, Robinson PP. The reinnervation of the tongue and salivary glands after two methods of lingual nerve repair in the cat. Arch Oral Biol 1995;40: 373–83. 69. Smith KG, Robinson PP. The re-innervation of the tongue and salivary glands after lingual nerve repair by stretch, sural nerve graft or frozen muscle graft. J Dent Res 1995;74:1850–60. 70. Holland GR, Robinson PP. Axon populations in cat lingual and chorda tympani nerves. J Dent Res 1992; 71:1468–72. 71. Pogrel MA, Thamby S. The etiology of altered sensation in the inferior alveolar, lingual, and mental nerves as a result of dental treatment. J Calif Dent Assoc 1999;27:531, 534–8. 72. Pogrel MA, Kaban LB. Injuries to the inferior alveolar and lingual nerves. J Calif Dent Assoc 1993;21:50–4. 73. Gregg JM. Studies of traumatic neuralgias in the maxillofacial region: surgical pathology and neural mechanisms. J Oral Maxillofac Surg 1990;48:228–37; discussion 238–9.
10
Use of the dog and cat in experimental maxillofacial surgery M. Anthony Pogrel & Xudong Wang The use of dogs and cats as animal models for human research has a long history which is often arbitrary, and not always based on science. In fact, the use of animal models in general has a somewhat checkered history, both scientifically and emotionally. At the present time, attempts are being made to move away from live animal models as much as possible, and to move to the use of simulation, biomimetics and tissue cultures, etc. Where animal models need to be used, an attempt has been made to move to smaller animals, including rodents, for studies where size is not an important part of the study. However, instances still remain where it is required to use an animal that is large enough to render simulation as realistic as possible to obtain realistic results. Primates have always been felt to be the most realistic animal models for human research, but costs have increased such as to make them unusable for anything but the largest studies. Dogs and cats have been used extensively, but their use is decreasing because of noted differences in size, biology and physiology between dogs and cats and humans, and also cost issues and psychological issues related to the use of animals which are also domestic pets. Animals such as pigs,1–3 sheep4–6 and goats7–9 are becoming more frequently used as animal models, in part because of the larger and more realistic size, biological similarities to humans,3,10–12 and also because there may be less emotion attached to their use.
DOGS In the maxillofacial region, dogs have a long history of use as an animal model, usually for hard tissue (bone and teeth) research, but also for soft tissue studies. The rationale often given for the use of dogs is that their size makes them large enough for realistic surgical procedures to be carried out. In fact, studies have shown that in some respects they are about the smallest animal that can be used for some realistic studies of human maxillofacial procedures. Their teeth are also of similar size and pulpal pattern to those of humans, and they have similar periodontal ligament attachments as human teeth.13,14 The bony architecture of the mandible and maxilla is also similar to humans with Haversian systems (unlike rats), and they are the © 2012 Elsevier Ltd DOI: 10.1016/B978-0-7020-4618-6.00010-5
smallest animals with a similar pattern of bone remodeling to humans.15,16 Growth, remodeling, structural and chemical properties, and mineralization of bone is similar to that of humans. Age-related bony changes are also similar to humans.17 They are cooperative animals, and there is often no need for general anesthesia for relatively simple procedures such as obtaining photographs, making measurements, and even procedures such as cleaning teeth, or adjusting dental appliances or braces. This can be a considerable advantage in some studies.
Bone turnover It is generally agreed that the bone turnover time in dogs is faster than that in humans, and that fractures heal more rapidly in dogs than humans.18 However the process of fracture healing in dogs is essentially similar to that in humans.18 Bone turnover time is normally expressed as sigma, which is one complete bone turnover cycle, including both a resorptive phase and an appositional phase.19–23 This time for the beagle is felt to be two to three times that of a human,23–28 though other studies have suggested it is around 1.5 times as great.29 Variations are possible for a number of reasons. It is known that variations occur within the same species of dogs, and certainly there are variations between species of dogs. There is also a variation depending on age. It must be remembered that most animal experiments involving dogs are carried out on fairly young dogs, usually for financial reasons, whilst equivalent human operations may be carried out on more mature humans. Bone turnover is obviously going to be more rapid in younger animals. There are also variations in bone turnover time for cortical bone versus medullary bone, and this should be taken into account when studies are compared. Studies carried out on animals may not therefore be directly transferred to humans,15 or even to clinical veterinary practice. The critical size defect has been established for the canine cranium at around 20 mm, and for the canine mandible it is at 15 mm if the periosteum is removed and 50 mm if it is intact.30,31 A critical size defect is one which, if created, will not heal spontaneously. Critical size defects are used for research on bone grafting and reconstruction techniques involving a variety of osteoconductive and osteoinductive agents.32,33
93
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Surgical methods
Facial growth As we move away from the use of primates in maxillofacial studies, dogs have been examined for their use in a number of studies of facial growth. Losken et al. determined that the mandibular growth pattern of the dog shows similar relative percentage changes in different regions in juvenile through adult stages, as do those of the human being, and suggested that dogs may be an acceptable, inexpensive alternative to primates in certain maxillofacial growth situations.34 Similarly, dogs have also been studied for their ability to be used as spontaneous animal models of human disease. For example, many dogs suffer from maxillary brachygnathism as a natural phenomenon. In fact, it is even a requirement in the official standards established for certain breeds, including the English toy spaniel, French bulldog, English bulldog and boxers.35 Brachycephaly in dogs is a regional manifestation of achondroplasia, and occurs naturally in some breeds.35 Hereditary multiple exostosis has also been recognized to occur in several breeds including the West Highland white terrier, cairn and Boston terriers, Great Danes and Labrador retrievers.36 Data suggest that these animals may make suitable models for investigation of the etiology and treatment of infantile cortical hyperostosis in human infants.36,37 Dogs have also been used in studies involving orthognathic surgery and tooth viability.13
Periodontal disease The beagle suffers naturally from periodontal disease and periodontal degeneration, and has been widely used in studies of periodontal disease and in evaluations of a variety of surgical and nonsurgical treatments of periodontal disease.14,38 More recently, the beagle has been used in studies utilizing membrane technology as a method of treating periodontal disease in humans.39,40 Postoperative infection rates are extremely low in dogs, and this may also need to be taken into account in studies of healing following certain procedures. Single genomic beagle models have recently been developed which should lead to more standardization of research data. Soft tissue studies on dogs have included grafting materials for vestibuloplasty (increasing the amount of gingiva for dentures to rest on).41
Implants Dogs have also been used extensively in studies on various aspects of osteointegrated dental implants for tooth replacement, including osteointegration time, degree of osteointegration, effects of early and late loading, and the effects of orthodontic forces.42–50 Some of these studies have been combined with the use of growth factors.39,43 Although these studies have been valuable, it does need to be borne in mind that the bone turnover time is more rapid in dogs than in humans, and thus the studies may not be directly transferrable to the human situation or even to clinical veterinary practice. Despite the possible dissimilarities between bone healing in dogs and humans, the canine model has become popular for investigating the management of periodontal disease, both around natural teeth
and around implants, and the concept of a barrier membrane to encourage new bone growth. This has led to the concept of a criticalsize supra-alveolar periodontal defect and the related critical-size supra-alveolar peri-implant defect in the canine animal model. In the beagle dog model, this critical size defect is around 5 mm all around a natural tooth or implant.44,45
Distraction Dogs have also been used to look at various aspects of distraction osteogenesis, which is a more recent technique for slowly moving facial bones by means of gradual distraction following an initial osteotomy.51–54 Again, many of the parameters utilized in humans have been established from animal research utilizing dogs. However, it needs to be emphasized that the bone turnover rate is faster in dogs than in humans.
CATS The use of cats as experimental animals in oral and maxillofacial surgery is not found as frequently as dogs, possibly because they are smaller animals and therefore may not be quite as realistic a model, and also because they are not as cooperative as dogs, and therefore may need anesthetizing more often for procedures to be carried out. Nevertheless, cats have been used for a variety of hard and soft tissue studies. They have been widely used for orthodontic studies involving tooth movement because the crown to root ratio and periodontal ligaments are similar to that of humans and therefore it is felt that the tooth movement obtained orthodontically on a cat may be realistically transferred to the human.55–58 Studies have shown that the cat may be the most realistic nonprimate model for nasal growth studies to simulate results in humans.59 In the soft tissues, studies involving the temporalis muscle have been carried out on cats, and this appears to be related to the fact that cats have a prominent temporalis muscle which is particularly amenable to surgical procedures.60–62
Nerve studies The cat has also been used for studies on the lingual and inferior alveolar nerves, with particular reference to the response of this nerve to injury, and spontaneous and surgically induced regeneration, and also the value of a number of nerve growth factors which may aid reconstruction and regrowth of the branches of the trigeminal nerve.63–70 The rationale for utilizing the cat for these studies appears to be that there is a long history of its use, and the cat appears to lend itself to carrying out single neuron studies on the branches of the trigeminal nerve, which can be extremely valuable in a number of physiological studies. Injury to the inferior alveolar and lingual nerves occurs in humans as a result of trauma and a variety of surgical procedures including wisdom tooth removal.71,72 Loss of sensation, or dysesthesia, causes considerable morbidity and hence the necessity for a reliable animal model.73
REFERENCES 1. Terheyden H, Knak C, Jepsen S, et al. Mandibular reconstruction with a prefabricated vascularized bone graft using recombinant human osteogenic protein-1: an experimental study in miniature pigs.
94
Part I: Prefabrication. Int J Oral Maxillofac Surg 2001;30:373–9. 2. Henkel KO, Ma L, Lenz JH, et al. Closure of vertical alveolar bone defects with guided horizontal distraction osteogenesis:
an experimental study in pigs and first clinical results. J Craniomaxillofac Surg 2001;29:249–53. 3. Troulis MJ, Glowacki J, Perrott DH, et al. Effects of latency and rate on bone
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