Imbalanced development of anterior and posterior thorax is a causative factor triggering scoliosis

Abstract

Objective: Scoliosis is a common disease characterized by spinal curvature with variable severities. There is no generally accepted theory about the physical origin of the spinal deformation of scoliosis. The aim of this study was to explore a new hypothesis suggesting that the curvatures in scoliosis may be associated with the imbalance growth between thoracic vertebral column and sternum.

Methods: We undertook a comparative computed tomography (CT) based morphology study of thoracic vertebrae and sternum of patients with adolescent idiopathic scoliosis (AIS) and age-gender matched normal subjects. We further measured the ratios between the lengths of the sternum and thoracic vertebra of mice with deficiency of fibroblast growth factor receptor 3 (FGFR3), which exhibit scoliosis. Three-week-old C57BL/6J mice were used to generate bipedal and sternal growth plate injury model. Radiographs and histological images were obtained to observe the presence of sternal and spinal deformity.

Results: There was a significant correlation between the severities of scoliosis and the ratios of the sternum to thoracic vertebral lengths. We also found that FGFR3 deficient mice showed smaller ratio of the sternum to thoracic vertebra lengths than that of the wild-type mice, which were similar with that of the AIS patients. Surgery-induced injuries of sternal growth plates can accelerate and aggravate the scoliosis in bipedal mice and imbalanced development of anterior and posterior thoracic occurred before the appearance of scoliosis.

Conclusions: Our findings suggest that the imbalanced growth between the thoracic vertebral column and the sternum is an important causative factor for the pathogenesis of scoliosis including AIS.

The translational potential of this article: Imbalanced growth between the thoracic vertebral column and the sternum is associated with scoliosis. Surgical or rehabilitation intervention for scoliosis should focus on all components involved in the pathogenesis of curvature to obtain better outcome.

Keywords: Growth plate; Imbalanced growth; Scoliosis; Sternum; Vertebrae.

Figure 1

The CT images and measurement results obtained from AIS patients and control subject. (A) Representative CT images of thorax in patients with AIS. (B) Representative CT images of thorax of individuals in the normal group. (C) The thoracic anteroposterior length ratio of patients with AIS was significantly decreased. Values are the mean ± SD. ****P < 0.0001 compared with normal group. AIS = adolescent idiopathic scoliosis; CT = computed tomography; SD = standard deviation.

Figure 2

FGFR3 deficiency results in scoliosis with decreased thoracic anteroposterior length ratio in mice. (A) Representative X-ray images of the sternum and thoracic vertebrae from WT and FGFR3-deficient mice at 2 and 8 weeks. (B) Representative 3D micro-CT images of thoracic vertebrae from WT and FGFR3-deficient mice at 8 weeks. (C) The length of thoracic vertebrae (T1–10) in FGFR3-deficient mice was increased compared with WT mice (n = 8). (D) Thoracic anteroposterior length ratio was significantly reduced in FGFR3-deficient mice (n = 8). (E) The histological section image of the affected thoracic vertebra and intervertebral disc. Red arrows point to apical vertebrae. Values are the mean ± SD. ***P < 0.001; ****P < 0.0001 compared with C3H mice. CT = computed tomography; SD = standard deviation; WT = wild-type.

Figure 3

Analysis of the thoracic anteroposterior length ratio in C57 and C3H mice. (A) The thoracic anteroposterior length ratio in C57 mice was gradually decreased with age in the development stage. (n = 5) (B) C57 mice exhibited significantly lower thoracic anteroposterior length ratios than C3H mice (n = 8) (C) Representative X-ray images of the sternum and thoracic vertebrae from C57 mice at postnatal 2 and 4 months. (D) Scatter plots illustrate that no scoliosis was developed during the development stage in C57 mice (n = 15). Values are the mean ± SD. ***P < 0.001 compared with C3H mice. SD = standard deviation.

Figure 4

Artificially reducing the thoracic anteroposterior length ratio by surgical destruction of growth plates (SGD) was sufficient to cause scoliosis in quadrupedal C57 mice and increase scoliosis curvature severity in bipedal mice. (A, B) Representative X-ray and histologic images of the sternum with or without SGD at 3 month after surgery. SGD led to shortened sternum. (C) Representative X-ray images of mice in four groups: 1, quadrupedal; 2, bipedal; 3, SGD; 4, bipedal with SGD. (D) SGD led to scoliosis in quadrupedal mice and increased scoliosis curvature severity in bipedal mice. (E) SGD led to reduced thoracic anteroposterior length ratio. Values are the mean ± SD (n = 15 mice per group). **P < 0.01, ***P < 0.001 compared with quadrupedal control mice (Group 1); ^###P < 0.001 compared with bipedal mice (Group 3). SD = standard deviation.

Figure 5

Schematic diagram of the relationship between the sternum and the thoracic vertebrae. (A, B) The schematic diagram of thoracic skeleton structure in normal individuals: (A) anteroposterior; (B) lateral. The diagram of thoracic skeleton structure in thoracic scoliosis patients with bending and rotation in lateral: (C) anteroposterior; (D) lateral. The blue regions represent the growth plates. T, thoracic vertebrae; ST, sternum. The orange regions are the T7–10 and Ribs 7–10, which are the major affected regions of thoracic scoliosis. The green regions are the T11–12 and Rib 11–12 (floating ribs).