The Veterinary Journal 200 (2014) 449–451
Contents lists available at ScienceDirect
The Veterinary Journal j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t v j l
Short Communication
The effect of kyphoscoliosis on intervertebral disc degeneration in dogs Kiterie Faller, Jacques Penderis, Catherine Stalin, Julien Guevar, Carmen Yeamans, Rodrigo Gutierrez-Quintana * School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, UK
A R T I C L E
I N F O
Article history: Accepted 19 March 2014 Keywords: Congenital Vertebral Malformation Intervertebral Disc Degeneration Kyphoscoliosis Kyphosis Scoliosis
A B S T R A C T
In people, abnormalities in vertebral column conformation, such as kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD) structure and composition. It was hypothesised that canine IVDs adjacent to a vertebral malformation undergo early degeneration. In a blinded retrospective study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance images using Pfirrmann’s grade. IVDs adjacent to a vertebral malformation had higher grades of degeneration than non-adjacent IVDs (P < 0.0001). There was an age-dependency, with dogs between 1 and 4 years showing higher grade of degeneration in adjacent than non-adjacent IVDs (P < 0.0001). Conversely, in older dogs, all IVDs – including the non-adjacents – showed degenerative signs, possibly due to normal aging. These results suggest that congenital vertebral malformation results in early degeneration of adjacent IVDs. © 2014 Elsevier Ltd. All rights reserved.
With aging, changes occur in intervertebral discs (IVD), resulting ultimately in IVD degeneration. However, changes in the normal local mechanical environment of the IVD result in earlier degeneration, as supported by studies in humans and experimentally in animals (Stokes and Iatridis, 2004; Grivas et al., 2011). In dogs with natural or surgical fusion of the vertebral column, accelerated degeneration of the IVDs adjacent to these regions has been demonstrated, this process is referred to as adjacent segment disease or ‘domino’ effect (Ortega et al., 2012). Little information is available regarding the effects of other local biomechanical changes on IVD degeneration in dogs. Previous studies in humans and animal models showed that kyphotic and/or scoliotic deformities accelerate IVD degeneration (Stokes and Iatridis, 2004; Grivas et al., 2011). These vertebral malformations are commonly seen in brachycephalic ‘screw-tailed’ breeds and offer a biological model to evaluate the effect of kyphoscoliosis on IVD degeneration in dogs (Done et al., 1975; Moissonnier et al., 2011). The aim of the present study was to investigate if congenital vertebral malformations causing kyphoscoliosis accelerate IVD degeneration in adjacent IVD spaces in dogs. University of Glasgow medical records were retrospectively reviewed from September 2009 to April 2013 to identify French bulldogs, English bulldogs, Boston terriers and Pugs with magnetic
* Corresponding author. Tel.: +44 141 3305848. E-mail address: [email protected] (R. Gutierrez-Quintana). http://dx.doi.org/10.1016/j.tvjl.2014.03.027 1090-0233/© 2014 Elsevier Ltd. All rights reserved.
resonance imaging (MRI) studies of the thoracic vertebral column (including a sagittal T2-weighted image sequence), with at least one congenital vertebral malformation causing kyphosis or scoliosis (see Supplementary material for MRI acquisition). For each thoracic IVD (T1-T2 to T12-T13 – except for one dog with only 12 thoracic vertebrae), the slice closest to mid-sagittal was selected and each IVD was then individually cropped using Adobe Photoshop Elements Editor 11. The IVDs from all dogs were randomised twice by computer to ensure blinding to both dog identity and IVD location. Each IVD was scored on two occasions one week apart by two observers using the Pfirrmann grade, previously described in humans (Pfirrmann et al., 2001) and dogs (Bergknut et al., 2011). To determine whether the degree of degeneration was higher for IVDs directly adjacent to the vertebral malformation (IVD cranial and caudal to the malformation), the mode of the four scores assigned (two scores per observer) was calculated for each IVD. When two scores had been given with the same frequency, the higher value was assigned. Adjacent IVDs were then compared to non-adjacent IVDs using a chi-square test. A Spearman-rank test was used to test the correlation between age and IVD degeneration. The effect of age on degeneration of adjacent versus non-adjacent IVD was assessed by assigning the dogs to one of three age groups: 4 years (n = 4), before applying Kruskal-Wallis and Dunn’s post-hoc tests. Differences were considered significant for P < 0.05. Statistical analysis was performed using GraphPad Prism v.5.0. Finally, inter- and intra-observer agreement was also assessed (see Supplementary material).
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K. Faller et al./The Veterinary Journal 200 (2014) 449–451
Table 1 Frequency of intervertebral disc (IVD) degeneration grade for adjacent and nonadjacent IVDs. Grade
Number of adjacent IVDs (%)
Number of non-adjacent IVDs (%)
1 2 3 4 5 Total
6 (12%) 7 (13%) 14 (27%) 9 (17%) 16 (31%) 52 (100%)
39 (34%) 36 (31%) 22 (19%) 11 (10%) 7 (6%) 115 (100%)
Fourteen dogs fulfilled the inclusion criteria: ten male and four female. There were eight Pugs, four English Bulldogs and two French Bulldogs. Mean age at the time of MRI was 1.5 years (SD: 2.6 years) ranging from 3 months to 7.6 years. Six dogs had one vertebral malformation, three had two, three had three and two had four vertebral malformations. All malformations were caused by a defect of vertebral body formation, with the majority occurring at T7 and T8 (seven and six occurrences, respectively). There was a significant difference in the degree of degeneration of IVDs adjacent to the vertebral malformation as compared to the other IVDs (P < 0.0001) (Table 1). For almost all IVD locations, the degree of degeneration of IVDs adjacent to a vertebral abnormality was higher than non-adjacent IVDs (Figs. 1, 2). There was also a good correlation between the age of the dog and the degree
of IVD degeneration, independent of whether the IVD was adjacent to a vertebral malformation or not (r = 0.5, P < 0.001 when all IVDs were considered; r = 0.7, P < 0.001 when only adjacent IVDs were considered and r = 0.5, P < 0.001 when only non-adjacent IVDs were considered). In the group aged 1 to 4 years, the degree of degeneration of the adjacent IVD was marked compared to non-adjacent IVD (Fig. 3). However, in the older group, all IVDs irrespective of their location tended to show degenerative signs. The study showed that congenital vertebral malformations associated with kyphoscoliosis accelerated IVD degeneration in the adjacent IVD spaces. In order to be blinded, the IVDs were cropped individually before randomisation twice and scoring. This was considered to be an important part of the methodology due to the obvious vertebral malformations. Arguably, the blinding was possibly not perfect due to shape distortion of some IVDs adjacent to a vertebral abnormality. Animal model studies suggest that changes in the mechanical environment of the IVD disturb the fine balance between overloading of IVDs, causing ‘wear and tear’, and underloading of IVDs, disrupting normal structure and composition (Stokes and Iatridis, 2004). Asymmetrical loading could be responsible for the IVD degeneration observed in teenagers with idiopathic scoliosis and in animal models, due to changes in cell metabolism and in biochemical composition (Antoniou et al., 2001; Bibby et al., 2002; Grivas et al., 2011). In human patients with scoliosis, these structural changes do not result in obvious degeneration on MRI; subtle signs suggestive of
Fig. 1. Degree of intervertebral disc degeneration depending on intervertebral disc number and whether the intervertebral disc was adjacent to a vertebral abnormality. The degree of IVD degeneration was assessed on magnetic resonance images using the Pfirrmann’s grading system (grade 1 = no sign of degeneration and grade 5 = endstage degeneration). The number of intervertebral discs for each category is detailed on the graph. The dots outside the box and whisker plot represent outliers.
Fig. 2. Mid-sagittal T2-weighted image of a 7 month-old Pug with vertebral abnormalities at T5, T6, T9 and T10 (arrows). Note the degree of degeneration of the intervertebral discs adjacent to the sites of vertebral abnormality. The degree of degeneration was assessed using Pfirrmann’s grading system (grade 1 = no sign of degeneration and grade 5 = end-stage degeneration).
K. Faller et al./The Veterinary Journal 200 (2014) 449–451
451
severity of the vertebral malformation. A further limitation of our study lies in the intrinsic characteristic of these dogs with marked deviation of the vertebral column as a true midsagittal plane was not available for some IVDs and the use of parasagittal or oblique planes may have resulted in an overestimation of the degree of degeneration in some IVDs. Nevertheless, this blinded retrospective study showed that vertebral malformations associated with kyphoscoliosis resulted in early degeneration of IVDs adjacent to the malformation. Conflict of interest statement None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper. Acknowledgements
Fig. 3. Degree of intervertebral disc degeneration as a function of age and whether the intervertebral disc was adjacent to a vertebral abnormality. Dogs were stratified in three age groups. The degree of degeneration was assessed using Pfirrmann’s grading system (grade 1 = no sign of degeneration and grade 5 = end-stage degeneration). The number of intervertebral discs for each category is detailed on the graph. The dots outside the box and whisker plot represent outliers. All six groups were compared using a Kruskal-Wallis test (P < 0.0001) and Dunn’s multiple comparison test. ** denotes P < 0.01 and *** P < 0.001.
The authors are grateful to Dr Timothy Parkin for his help with the statistical analysis. Appendix A: Supplementary material Supplementary data associated with this article can be found in the online version at doi:10.1016/j.tvjl.2014.03.027 References
early degeneration can be seen, but only with thorough postprocessing analysis of the images (Gervais et al., 2012). Conversely, the degree of IVD degeneration seen here is marked. Species differences and especially the chondrodystrophic nature of the dogs selected for our study may explain some of this discrepancy. These dogs were also possibly suffering from a particularly pronounced vertebral malformation, as the severity of IVD degeneration tends to be linked to the degree of malformation (Grivas et al., 2011) Kyphoscoliotic vertebral malformation is a frequent congenital abnormality in the ‘screw-tailed’ breeds. Early IVD degeneration in these breeds should therefore be considered. However, the most frequently affected vertebrae here were T7 and T8, which is similar to the previously published reports (mostly between T5 and T9) (Done et al., 1975; Moissonnier et al., 2011). Considering the low prevalence of IVD extrusion in the thoracic spine, the clinical implication of this early IVD degeneration is unknown. The main limitation of our study was the small number of cases. However, due to the marked effect of vertebral malformation on IVD degeneration, this had no influence on the main conclusion. The malformations were also heterogeneous with different degrees of kyphosis and scoliosis. A larger sample size would have allowed classification of the degree of IVD degeneration on the basis of the
Antoniou, J., Arlet, V., Goswami, T., Aebi, M., Alini, M., 2001. Elevated synthetic activity in the convex side of scoliotic intervertebral discs and endplates compared with normal tissues. Spine 26, E198–E206. Bergknut, N., Auriemma, E., Wijsman, S., Voorhout, G., Hagman, R., Lagerstedt, A.-S., Hazewinkel, H.A.W., Meij, B.P., 2011. Evaluation of intervertebral disk degeneration in chondrodystrophic and nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low-field magnetic resonance imaging. American Journal of Veterinary Research 72, 893–898. Bibby, S.R.S., Fairbank, J.C.T., Urban, M.R., Urban, J.P.G., 2002. Cell viability in scoliotic discs in relation to disc deformity and nutrient levels. Spine 27, 2220–2228. Done, S.H., Drew, R.A., Robins, G.M., Lane, J.G., 1975. Hemivertebra in the dog: clinical and pathological observations. Veterinary Record 96, 313–317. Gervais, J., Perie, D., Parent, S., Labelle, H., Aubin, C.-E., 2012. MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis. BMC Musculoskeletal Disorders 13, 239. Grivas, T.B., Vasiliadis, E.S., Kaspiris, A., Khaldi, L., Kletsas, D., 2011. Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat’s intervertebral disc after experimentally induced scoliotic deformity. Scoliosis 6, 9. Moissonnier, P., Gossot, P., Scotti, S., 2011. Thoracic kyphosis Associated with Hemivertebra. Veterinary Surgery 40, 1029–1032. Ortega, M., Gonçalves, R., Haley, A., Wessmann, A., Penderis, J., 2012. Spondylosis deformans and diffuse iodiopathic skeletal hyperostosis (DISH) resulting in adjacent segment disease. Veterinary Radiology and Ultrasound 53, 128–134. Pfirrmann, C.W., Metzdorf, A., Zanetti, M., Hodler, J., Boos, N., 2001. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26, 1873–1878. Stokes, I.A.F., Iatridis, J.C., 2004. Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization. Spine 29, 2724–2732.
Contents lists available at ScienceDirect
The Veterinary Journal j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t v j l
Short Communication
The effect of kyphoscoliosis on intervertebral disc degeneration in dogs Kiterie Faller, Jacques Penderis, Catherine Stalin, Julien Guevar, Carmen Yeamans, Rodrigo Gutierrez-Quintana * School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, UK
A R T I C L E
I N F O
Article history: Accepted 19 March 2014 Keywords: Congenital Vertebral Malformation Intervertebral Disc Degeneration Kyphoscoliosis Kyphosis Scoliosis
A B S T R A C T
In people, abnormalities in vertebral column conformation, such as kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD) structure and composition. It was hypothesised that canine IVDs adjacent to a vertebral malformation undergo early degeneration. In a blinded retrospective study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance images using Pfirrmann’s grade. IVDs adjacent to a vertebral malformation had higher grades of degeneration than non-adjacent IVDs (P < 0.0001). There was an age-dependency, with dogs between 1 and 4 years showing higher grade of degeneration in adjacent than non-adjacent IVDs (P < 0.0001). Conversely, in older dogs, all IVDs – including the non-adjacents – showed degenerative signs, possibly due to normal aging. These results suggest that congenital vertebral malformation results in early degeneration of adjacent IVDs. © 2014 Elsevier Ltd. All rights reserved.
With aging, changes occur in intervertebral discs (IVD), resulting ultimately in IVD degeneration. However, changes in the normal local mechanical environment of the IVD result in earlier degeneration, as supported by studies in humans and experimentally in animals (Stokes and Iatridis, 2004; Grivas et al., 2011). In dogs with natural or surgical fusion of the vertebral column, accelerated degeneration of the IVDs adjacent to these regions has been demonstrated, this process is referred to as adjacent segment disease or ‘domino’ effect (Ortega et al., 2012). Little information is available regarding the effects of other local biomechanical changes on IVD degeneration in dogs. Previous studies in humans and animal models showed that kyphotic and/or scoliotic deformities accelerate IVD degeneration (Stokes and Iatridis, 2004; Grivas et al., 2011). These vertebral malformations are commonly seen in brachycephalic ‘screw-tailed’ breeds and offer a biological model to evaluate the effect of kyphoscoliosis on IVD degeneration in dogs (Done et al., 1975; Moissonnier et al., 2011). The aim of the present study was to investigate if congenital vertebral malformations causing kyphoscoliosis accelerate IVD degeneration in adjacent IVD spaces in dogs. University of Glasgow medical records were retrospectively reviewed from September 2009 to April 2013 to identify French bulldogs, English bulldogs, Boston terriers and Pugs with magnetic
* Corresponding author. Tel.: +44 141 3305848. E-mail address: [email protected] (R. Gutierrez-Quintana). http://dx.doi.org/10.1016/j.tvjl.2014.03.027 1090-0233/© 2014 Elsevier Ltd. All rights reserved.
resonance imaging (MRI) studies of the thoracic vertebral column (including a sagittal T2-weighted image sequence), with at least one congenital vertebral malformation causing kyphosis or scoliosis (see Supplementary material for MRI acquisition). For each thoracic IVD (T1-T2 to T12-T13 – except for one dog with only 12 thoracic vertebrae), the slice closest to mid-sagittal was selected and each IVD was then individually cropped using Adobe Photoshop Elements Editor 11. The IVDs from all dogs were randomised twice by computer to ensure blinding to both dog identity and IVD location. Each IVD was scored on two occasions one week apart by two observers using the Pfirrmann grade, previously described in humans (Pfirrmann et al., 2001) and dogs (Bergknut et al., 2011). To determine whether the degree of degeneration was higher for IVDs directly adjacent to the vertebral malformation (IVD cranial and caudal to the malformation), the mode of the four scores assigned (two scores per observer) was calculated for each IVD. When two scores had been given with the same frequency, the higher value was assigned. Adjacent IVDs were then compared to non-adjacent IVDs using a chi-square test. A Spearman-rank test was used to test the correlation between age and IVD degeneration. The effect of age on degeneration of adjacent versus non-adjacent IVD was assessed by assigning the dogs to one of three age groups: 4 years (n = 4), before applying Kruskal-Wallis and Dunn’s post-hoc tests. Differences were considered significant for P < 0.05. Statistical analysis was performed using GraphPad Prism v.5.0. Finally, inter- and intra-observer agreement was also assessed (see Supplementary material).
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K. Faller et al./The Veterinary Journal 200 (2014) 449–451
Table 1 Frequency of intervertebral disc (IVD) degeneration grade for adjacent and nonadjacent IVDs. Grade
Number of adjacent IVDs (%)
Number of non-adjacent IVDs (%)
1 2 3 4 5 Total
6 (12%) 7 (13%) 14 (27%) 9 (17%) 16 (31%) 52 (100%)
39 (34%) 36 (31%) 22 (19%) 11 (10%) 7 (6%) 115 (100%)
Fourteen dogs fulfilled the inclusion criteria: ten male and four female. There were eight Pugs, four English Bulldogs and two French Bulldogs. Mean age at the time of MRI was 1.5 years (SD: 2.6 years) ranging from 3 months to 7.6 years. Six dogs had one vertebral malformation, three had two, three had three and two had four vertebral malformations. All malformations were caused by a defect of vertebral body formation, with the majority occurring at T7 and T8 (seven and six occurrences, respectively). There was a significant difference in the degree of degeneration of IVDs adjacent to the vertebral malformation as compared to the other IVDs (P < 0.0001) (Table 1). For almost all IVD locations, the degree of degeneration of IVDs adjacent to a vertebral abnormality was higher than non-adjacent IVDs (Figs. 1, 2). There was also a good correlation between the age of the dog and the degree
of IVD degeneration, independent of whether the IVD was adjacent to a vertebral malformation or not (r = 0.5, P < 0.001 when all IVDs were considered; r = 0.7, P < 0.001 when only adjacent IVDs were considered and r = 0.5, P < 0.001 when only non-adjacent IVDs were considered). In the group aged 1 to 4 years, the degree of degeneration of the adjacent IVD was marked compared to non-adjacent IVD (Fig. 3). However, in the older group, all IVDs irrespective of their location tended to show degenerative signs. The study showed that congenital vertebral malformations associated with kyphoscoliosis accelerated IVD degeneration in the adjacent IVD spaces. In order to be blinded, the IVDs were cropped individually before randomisation twice and scoring. This was considered to be an important part of the methodology due to the obvious vertebral malformations. Arguably, the blinding was possibly not perfect due to shape distortion of some IVDs adjacent to a vertebral abnormality. Animal model studies suggest that changes in the mechanical environment of the IVD disturb the fine balance between overloading of IVDs, causing ‘wear and tear’, and underloading of IVDs, disrupting normal structure and composition (Stokes and Iatridis, 2004). Asymmetrical loading could be responsible for the IVD degeneration observed in teenagers with idiopathic scoliosis and in animal models, due to changes in cell metabolism and in biochemical composition (Antoniou et al., 2001; Bibby et al., 2002; Grivas et al., 2011). In human patients with scoliosis, these structural changes do not result in obvious degeneration on MRI; subtle signs suggestive of
Fig. 1. Degree of intervertebral disc degeneration depending on intervertebral disc number and whether the intervertebral disc was adjacent to a vertebral abnormality. The degree of IVD degeneration was assessed on magnetic resonance images using the Pfirrmann’s grading system (grade 1 = no sign of degeneration and grade 5 = endstage degeneration). The number of intervertebral discs for each category is detailed on the graph. The dots outside the box and whisker plot represent outliers.
Fig. 2. Mid-sagittal T2-weighted image of a 7 month-old Pug with vertebral abnormalities at T5, T6, T9 and T10 (arrows). Note the degree of degeneration of the intervertebral discs adjacent to the sites of vertebral abnormality. The degree of degeneration was assessed using Pfirrmann’s grading system (grade 1 = no sign of degeneration and grade 5 = end-stage degeneration).
K. Faller et al./The Veterinary Journal 200 (2014) 449–451
451
severity of the vertebral malformation. A further limitation of our study lies in the intrinsic characteristic of these dogs with marked deviation of the vertebral column as a true midsagittal plane was not available for some IVDs and the use of parasagittal or oblique planes may have resulted in an overestimation of the degree of degeneration in some IVDs. Nevertheless, this blinded retrospective study showed that vertebral malformations associated with kyphoscoliosis resulted in early degeneration of IVDs adjacent to the malformation. Conflict of interest statement None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper. Acknowledgements
Fig. 3. Degree of intervertebral disc degeneration as a function of age and whether the intervertebral disc was adjacent to a vertebral abnormality. Dogs were stratified in three age groups. The degree of degeneration was assessed using Pfirrmann’s grading system (grade 1 = no sign of degeneration and grade 5 = end-stage degeneration). The number of intervertebral discs for each category is detailed on the graph. The dots outside the box and whisker plot represent outliers. All six groups were compared using a Kruskal-Wallis test (P < 0.0001) and Dunn’s multiple comparison test. ** denotes P < 0.01 and *** P < 0.001.
The authors are grateful to Dr Timothy Parkin for his help with the statistical analysis. Appendix A: Supplementary material Supplementary data associated with this article can be found in the online version at doi:10.1016/j.tvjl.2014.03.027 References
early degeneration can be seen, but only with thorough postprocessing analysis of the images (Gervais et al., 2012). Conversely, the degree of IVD degeneration seen here is marked. Species differences and especially the chondrodystrophic nature of the dogs selected for our study may explain some of this discrepancy. These dogs were also possibly suffering from a particularly pronounced vertebral malformation, as the severity of IVD degeneration tends to be linked to the degree of malformation (Grivas et al., 2011) Kyphoscoliotic vertebral malformation is a frequent congenital abnormality in the ‘screw-tailed’ breeds. Early IVD degeneration in these breeds should therefore be considered. However, the most frequently affected vertebrae here were T7 and T8, which is similar to the previously published reports (mostly between T5 and T9) (Done et al., 1975; Moissonnier et al., 2011). Considering the low prevalence of IVD extrusion in the thoracic spine, the clinical implication of this early IVD degeneration is unknown. The main limitation of our study was the small number of cases. However, due to the marked effect of vertebral malformation on IVD degeneration, this had no influence on the main conclusion. The malformations were also heterogeneous with different degrees of kyphosis and scoliosis. A larger sample size would have allowed classification of the degree of IVD degeneration on the basis of the
Antoniou, J., Arlet, V., Goswami, T., Aebi, M., Alini, M., 2001. Elevated synthetic activity in the convex side of scoliotic intervertebral discs and endplates compared with normal tissues. Spine 26, E198–E206. Bergknut, N., Auriemma, E., Wijsman, S., Voorhout, G., Hagman, R., Lagerstedt, A.-S., Hazewinkel, H.A.W., Meij, B.P., 2011. Evaluation of intervertebral disk degeneration in chondrodystrophic and nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low-field magnetic resonance imaging. American Journal of Veterinary Research 72, 893–898. Bibby, S.R.S., Fairbank, J.C.T., Urban, M.R., Urban, J.P.G., 2002. Cell viability in scoliotic discs in relation to disc deformity and nutrient levels. Spine 27, 2220–2228. Done, S.H., Drew, R.A., Robins, G.M., Lane, J.G., 1975. Hemivertebra in the dog: clinical and pathological observations. Veterinary Record 96, 313–317. Gervais, J., Perie, D., Parent, S., Labelle, H., Aubin, C.-E., 2012. MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis. BMC Musculoskeletal Disorders 13, 239. Grivas, T.B., Vasiliadis, E.S., Kaspiris, A., Khaldi, L., Kletsas, D., 2011. Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat’s intervertebral disc after experimentally induced scoliotic deformity. Scoliosis 6, 9. Moissonnier, P., Gossot, P., Scotti, S., 2011. Thoracic kyphosis Associated with Hemivertebra. Veterinary Surgery 40, 1029–1032. Ortega, M., Gonçalves, R., Haley, A., Wessmann, A., Penderis, J., 2012. Spondylosis deformans and diffuse iodiopathic skeletal hyperostosis (DISH) resulting in adjacent segment disease. Veterinary Radiology and Ultrasound 53, 128–134. Pfirrmann, C.W., Metzdorf, A., Zanetti, M., Hodler, J., Boos, N., 2001. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26, 1873–1878. Stokes, I.A.F., Iatridis, J.C., 2004. Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization. Spine 29, 2724–2732.
