Adolescent idiopathic scoliosis: The mechanobiology of differential growth

Abstract

Adolescent idiopathic scoliosis (AIS) has been linked to neurological, genetic, hormonal, microbial, and environmental cues. Physically, however, AIS is a structural deformation, hence an adequate theory of etiology must provide an explanation for the forces involved. Earlier, we proposed differential growth as a possible mechanism for the slow, three-dimensional deformations observed in AIS. In the current perspective paper, the underlying mechanobiology of cells and tissues is explored. The musculoskeletal system is presented as a tensegrity-like structure, in which the skeletal compressive elements are stabilized by tensile muscles, ligaments, and fasciae. The upright posture of the human spine requires minimal muscular energy, resulting in less compression, and stability than in quadrupeds. Following Hueter-Volkmann Law, less compression allows for faster growth of vertebrae and intervertebral discs. The substantially larger intervertebral disc height observed in AIS patients suggests high intradiscal pressure, a condition favorable for notochordal cells; this promotes the production of proteoglycans and thereby osmotic pressure. Intradiscal pressure overstrains annulus fibrosus and longitudinal ligaments, which are then no longer able to remodel and grow, and consequently induce differential growth. Intradiscal pressure thus is proposed as the driver of AIS and may therefore be a promising target for prevention and treatment.

Keywords: Hueter‐Volkmann law; adolescent idiopathic scoliosis; differential growth; intervertebral disc; notochordal cells; tensegrity.

FIGURE 1

An example of tensegrity: the 18 m high Needle Tower at the Hirshhorn Museum and Sculpture Garden, Washington D.C., designed by Kenneth Snelson. The rods are loaded under pure compression, the wires under pure tension. Picture by Saku Takakusaki

FIGURE 2

Muscular and gravity forces working on the body (62 kg) and the lumbar spine. In the situation drawn, the head, trunk and arms have a relatively large lever arm with respect to the joint center at L5‐S1. By contrast, the Mm. erectores spinae that counterbalance the resulting moment have a lever arm of only 6 cm. In the example drawn, the muscular force adds up to 2512 N, about four times body weight. Figure adapted from Grieve D, Phaesant S (1982): Biomechanics (Chapter 3). In: Singleton, WT, ed. Body at Work—Biological Ergonomics. Cambridge University Press, p.165

FIGURE 3

Rods buckling under axial compression. The mode of buckling strongly depends on the boundary conditions at the ends of the slender rod

FIGURE 4

Differential growth in a physical spine model. The distance between the vertebrae is expanded while the metal wires representing the ligaments restrict this. We see a gradual flattening of the thoracic kyphosis (blue dots) and an induced scoliosis which starts slowly and increases exponentially after reaching instability (red dots). Left an anterior view on the original position of the spine with a Cobb angle of 7°, right the situation at the end of the experiment. Note that the vertebrae also show substantial axial rotation, For further details, see Crijns et al ¹⁵

FIGURE 5

Tension in the ligaments and annulus fibrosus. A, Intervertebral disc height diurnal changes from morning (left) to evening (middle). In the case of AIS, intervertebral disc height is strongly increased by increased disc pressure, counterbalanced with higher tension in ligaments and annulus fibrosus (right). B, Typical bi‐linear elasticity of ligaments, with low stiffness in the toe‐region (green) and high stiffness in the strained region (red)

FIGURE 6

Spinal compression and stresses in the intervertebral disc. The spine is mainly loaded under axial compression (F _compr), which results in a deformation and a stress in the intervertebral disc. Stresses can mathematically be divided into two components: an all‐sided pressure p which reduces the volume and remains shape; and a distortional shear stress which maintains the volume of the matrix but changes shape. Hydraulic stress drives the fluid flow which is necessary for the transport of nutrients and waste products and secures the vitality of the cells. Notochordal cells and chondrocytes thrive under hydrostatic pressure and respond by proliferation and matrix production, leading to growth. Shear stress, by contrast, induces katabolic and inflammatory gene expression, leading to apoptosis and matrix breakdown. The balance between hydraulic and shear stress determines cellular response and growth of the intervertebral disc