Intervertebral disc degeneration

Biomechanics

IVDs are “cushion”-like structures that support and evenly distribute the compressive and bending stresses acting upon the spine (see Chapters 1 and 2 ). Changes in the loading pattern, intensity, and duration of loading increase the risk of IVD [ , ]. Continuous and excessive static compression is believed to cause more damage to the disc than cyclic compression [ ]. Experiments performed on cadaveric motion segments have shown mechanical disc failure following prolonged compressive loading due to a break in the integrity of the endplate (see Chapter 10 ). Fracture of the adjacent endplate may be caused by a reduction in the hydrostatic pressure of the NP. Thereafter, the resistance to compressive force is mediated by the AF [ ], leading to the formation of stress peaks, particularly in the posterior AF [ ]. A nonsupporting NP gives way to the unstable inner AF, and it may buckle inwards [ , ], leading to disruption of the remaining tissue [ ]. The pressure gradients and stress peaks break the inter- and intralamellar connections of the annular fibers resulting in delamination and separation resulting in tears and fissures [ ].

It is suggested that the prolapse of the IVD might be a consequence of rotation and bending motions combined with compressive forces (see Chapter 8 ) [ , ]; these motions, when combined, are likely to produce radial fissures of the AF due to fatigue failure [ , ]. Torsion, another critical component of loading, is also thought to increase posterolateral stress leading to prolapse [ ]. The depressurized NP and fissured AF of the prolapsed IVD cannot resist the bending movement because there is an increase in the intralamellar shear stress, causing further mechanical disruption [ ].

All of these asymmetrical loading patterns, stress gradients, and tissue deformation are reported to affect the extracellular matrix and cellular organization of the IVD [ ]. Gene expression of both aggrecan and collagen II is downregulated [ , ], along with altered gene expression for specific matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) [ ]. Walter et al. [ ] reported mechanically induced cell death and a “shift toward catabolism” due to bending movements combined with compressive stress. IVDs with altered metabolism and diminished cells experience a chronic state of distress, leading to IVD degeneration [ ].

Altered loading patterns have been reproduced in many in vitro studies. Injuries to the IVDs and endplates of human cadaveric motion segments and in animal models were experimentally induced to determine their influence on IVD degeneration (see Chapters 3 and 4 ) [ , ]. The cut injury to the peripheral AF of sheep IVDs affirmed the role of tears and fissures in degeneration [ ]. Furthermore, human cadaveric studies helped demonstrate the role of endplate fracture in altering compressive load distribution in AF injuries [ ]. Reduction in the GAG content, upregulation of MMPs and cytokines, necrotic, and apoptotic cell death all are consequences of mechanically induced injuries to the endplate [ , ]. Similarly, a mechanically injured IVD causes upregulation of proteolytic enzymes and proteoglycan loss, releasing neurotrophins capable of promoting neuronal ingrowth and sensitization, which may link IVD degeneration and LBP [ ].

Nutrition

The avascular IVD deals with nutritional challenges throughout its life. Very few blood vessels and nerves are responsible for supplying the margins of the peripheral AF, while the rest of the IVD depends for nutritional support on capillaries and blood vessels present at the bone–cartilage endplate junction [ ]. The process of diffusion and fluid flow is mainly responsible for the transport of nutrients and waste through the endplate route [ ]. Oxygen and glucose are very crucial for the well-being of IVD cells and reach the disc tissue via the process of diffusion; metabolic waste such as lactic acid follows the same process but in the opposite direction [ ]. To and from transport occurs through the bony endplate and the dense matrix of cartilaginous endplates to reach the cells of the central IVD tissue [ ]. Any structural or biochemical change in the bony or cartilaginous endplate may influence the diffusion process [ ]. Multiple studies on endplates have linked the calcification and resorption of the cartilaginous endplate (CEP) with degeneration (see Chapter 10 ) [ , ]. Calcification and sclerosis of the bony endplate were also held responsible for IVD degeneration and the possibility that occlusion of the openings with capillary buds could deprive the IVD of nutrients [ ]. But, other studies incorporating precise quantification of bone mass density with the help of a μCT scanner showed no significant association of bony endplate sclerosis with IVD degeneration [ ]. Rather, an increase in porosity and permeability was seen with increasing IVD degeneration grades and with age [ ]. All of these findings draw attention toward the CEP, calcification of which may be a permeability barrier to the solute transport, facilitating the process of IVD degeneration [ ].

Other factors causing any disturbance in the nutritional supply to the IVD might be attributed to pathological changes in adjacent blood vessels through which nutrients diffuse. Lumbosacral spine segments are supplied by the branches of the abdominal aorta and internal iliac arteries, and thence atherosclerosis of the aorta or segmental arteries may compromise the nutrient supply to the IVDs [ , ]. Constriction of the blood capillaries due to smoking or short-term vibration could also be a significant factor in reducing the diffusional transport across the IVD [ ].

Oxygen and glucose are the main nutrients required by IVDs cells to stay alive. Glucose is chiefly used to provide energy, producing lactic acid as a byproduct in a sufficiently high quantity. The concentration of glucose is a sensitive parameter required to maintain the viability of the cell [ ]. With a disturbance in the transport across the IVD, the low levels of glucose and an increased accumulation of lactate compromise the viability of the cells. Reduced pH decreases the rate of matrix component synthesis and activates the production of proteases [ ]. A study using 3D finite element analysis recorded a reduction in the cellular density with nutritional deprivation [ ], hence, supporting the notion of nutrition-related mechanisms in IVD degeneration.