Disturbance of rib cage development causes progressive thoracic scoliosis: the creation of a nonsurgical structural scoliosis model in mice.
BACKGROUND
The pathomechanism underlying idiopathic scoliosis remains unclear, and, to our knowledge, a consistent and relevant animal model has not been established previously. The goal of this study was to examine whether a disturbance of rib cage development is a causative factor for scoliosis and to establish a nonsurgical mouse model of progressive scoliosis.


METHODS
To examine the relationship between rib cage development and the pathogenesis of progressive scoliosis, a plastic restraint limiting anteroposterior rib cage development was placed on the chest of four-week-old mice. All mice were evaluated with whole-spine radiographs, and the severity of scoliosis was consecutively measured. The rib cage rotation angle and the anteroposterior chest dimension were measured with use of micro-computed tomography scanning. To examine whether the imbalanced load transmission through the ribs to the vertebral body was involved in our model, we performed a rib-neck osteotomy in a subgroup of the mice.


RESULTS
The thoracic restraint did not provoke spinal curvature immediately after it was applied, but nine of ten mice that wore the restraint but did not have rib osteotomy gradually developed progressive scoliosis. Radiographs and computed tomography images showed a right thoracic curvature, vertebral rotation, and narrow chest in the mice that had worn the restraint for eleven weeks but did not have rib osteotomy even after the restraint was removed. The anteroposterior chest dimension was significantly correlated with both the curve magnitude and the rib cage rotation angle. The progression of spinal deformity was observed only during the adolescent growth spurt, and it plateaued thereafter. The left-side rib osteotomy led to the development of progressive left-thoracic curvature, whereas the bilateral rib osteotomy did not cause scoliosis, even with restraint wear.


CONCLUSIONS
We established a nonsurgical experimental model of progressive scoliosis and also demonstrated that a rib cage deformity with an imbalanced load to the vertebral body resulted in progressive structural scoliosis.
Departments of Orthopaedic Surgery (K. Kubota, K. Kobayakawa, Y.M., K.H., Y.I.) and Advanced Medical Initiatives (M.M., M.H., S.O.), Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582. E-mail address fro K. Kubota: kkubot8@ortho.med.kyushu-u.ac.jp. E-mail address for M. Murata: m-murata@dem.med.kyushu-u.ac.jp. E-mail address for K. Kobyakawa: 0809kazu@ortho.med.kyushu-u.ac.jp. E-mail address for Y. Matsumoto: ymatsu@ortho.med.kyushu-u.ac.jp. E-mail address for K. Harimaya: harimaya@ortho.med.kyushu-u.ac.jp. E-mail address for M. Hashizume: mhashi@med.kyushu-u.ac.jp. E-mail address for Y. Iwamoto: yiwamoto@ortho.med.kyushu-u.ac.jp.
Kensuke
K
Kubota
Toshio
T
Doi
Masaharu
M
Murata
Kazu
K
Kobayakawa
Yoshihiro
Y
Matsumoto
Katsumi
K
Harimaya
Keiichiro
K
Shiba
Makoto
M
Hashizume
Yukihide
Y
Iwamoto
Seiji
S
Okada
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D012272:Ribs / Q000002:abnormalities* / Q000000981:diagnostic imaging; D012600:Scoliosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000601:surgery; D013131:Spine / Q000002:abnormalities* / Q000000981:diagnostic imaging; D035441:Thoracic Wall / Q000002:abnormalities* / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed