and Introduction Abstract Study Design: Review and reinterpretation of existing literature. Objective: To suggest how intervertebral disc degeneration might be distinguished from the physiologic processes of growth, aging, healing, and adaptive remodeling. Summary of Background Data: The research literature concerning disc degeneration is particularly diverse, and there are no accepted definitions to guide biomedical research, or medicolegal practice. Definitions: The process of disc degeneration is an aberrant, cell-mediated response to progressive structural failure. A degenerate disc is one with structural failure combined with accelerated or advanced signs of aging. Early degenerative changes should refer to accelerated age-related changes in a structurally intact disc. Degenerative disc disease should be applied to a degenerate disc that is also painful. Justification: Structural defects such as endplate fracture, radial fissures, and herniation are easily detected, unambiguous markers of impaired disc function. They are not inevitable with age and are more closely related to pain than any other feature of aging discs. Structural failure is irreversible because adult discs have limited healing potential. It also progresses by physical and biologic mechanisms, and, therefore, is a suitable marker for a degenerative process. Biologic progression occurs because structural failure uncouples the local mechanical environment of disc cells from the overall loading of the disc, so that disc cell responses can be inappropriate or aberrant. Animal models confirm that cell-mediated changes always follow structural failure caused by trauma. This definition of disc degeneration simplifies the issue of causality: excessive mechanical loading disrupts a disc's structure and precipitates a cascade of cell-mediated responses, leading to further disruption. Underlying causes of disc degeneration include genetic inheritance, age, inadequate metabolite transport, and loading history, all of which can weaken discs to such an extent that structural failure occurs during the activities of daily living. The other closely related definitions help to distinguish between degenerate and injured discs, and between discs that are and are not painful.

What is intervertebral disc degeneration, and what causes it?

Study design A review of the literature on disc nutrition. Objectives To summarize the information on disc nutrition in relation to disc degeneration. Summary of the background data The disc is avascular, and the disc cells depend on diffusion from blood vessels at the disc's margins to supply the nutrients essential for cellular activity and viability and to remove metabolic wastes such as lactic acid. The nutrient supply can fail due to changes in blood supply, sclerosis of the subchondral bone or endplate calcification, all of which can block transport from blood supply to the disc or due to changes in cellular demand. Methods A review of the studies on disc blood supply, solute transport, studies of solute transport in animal and human disc in vitro, and of theoretical modeling studies that have examined factors affecting disc nutrition. Results Small nutrients such as oxygen and glucose are supplied to the disc's cells virtually entirely by diffusion; convective transport, arising from load-induced fluid movement in and out of the disc, has virtually no direct influence on transport of these nutrients. Consequently, there are steep concentration gradients of oxygen, glucose, and lactic acid across the disc; oxygen and glucose concentrations are lowest in the center of the nucleus where lactic acid concentrations are greatest. The actual levels of concentration depend on the balance between diffusive transport and cellular demand and can fall to critical levels if the endplate calcifies or nutritional demand increases. Conclusions Loss of nutrient supply can lead to cell death, loss of matrix production, and increase in matrix degradation and hence to disc degeneration.

Nutrition of the intervertebral disc.

STUDY DESIGN A biomechanical and imaging study of human cadaveric spinal motion segments. OBJECTIVE To investigate the effect of both disc degeneration and facet joint osteoarthritis on lumbar segmental motion. SUMMARY OF BACKGROUND DATA Spinal degeneration includes the osteoarthritic changes of the facet joint as well as disc degeneration. Disc degeneration has been reported to be associated with spinal motion. The association of facet joint osteoarthritis with lumbar segmental motion characteristics and the combined influence of disc degeneration and facet osteoarthritis has not yet been investigated. METHODS A total of 110 lumbar motion segments (52 female, 58 male) from 44 human lumbar spines were studied (mean age = 69 years). Magnetic resonance images were used to assess the disc degeneration from Grade I (normal) to Grade V (advanced) and the osteoarthritic changes in the facet joints in terms of cartilage degeneration, subchondral sclerosis, and osteophytes. Disc height, endplate size, and facet joint orientation and width also were measured from the computed tomographic images. Rotational movements of the motion segment in response to the flexion, extension, lateral bending, and axial rotational moments were measured using a three-dimensional motion analysis system. RESULTS Female motion segments showed significantly greater motion (lateral bending: P < 0. 001, flexion: P < 0.01, extension: P < 0.05) and smaller endplate size (P < 0.001) than male ones. The segmental motion increased with increasing severity of disc degeneration up to Grade IV, but decreased in both genders when the disc degeneration advanced to Grade V. In male segments, the disc degeneration-related motion changes were significant in axial rotation (P < 0.001), lateral bending (P < 0.05), and flexion (P < 0.05), whereas female segments showed significant changes only in axial rotation (P < 0.001). With cartilage degeneration of the facet joints, the axial rotational motion increased, whereas the lateral bending and flexion motion decreased in female segments. In male segments, however, motion in all directions increased with Grade 3 cartilage degeneration and decreased with Grade 4 cartilage degeneration. Subchondral sclerosis significantly decreased the motion (female: axial rotation, P < 0. 05; extension, P < 0.05 vs.- male:flexion,P < 0.05). Severity of osteophytes had no significant association with the segmental motion. CONCLUSION Axial rotational motion was most affected by disc degeneration, and the effects of disc degeneration on the motion were similar between genders. Facet joint osteoarthritis also affected segmental motion, and the influence differed for male and female spines. Further studies are needed to clarify whether the degenerative process of facet joint osteoarthritis differs between genders and how facet joint osteoarthritis affects the stability of the spinal motion segment.

The effect of disc degeneration and facet joint osteoarthritis on the segmental flexibility of the lumbar spine.

https://www.oarsijournal.com/article/S1063-4584(15)00877-8/pdf

Mechanics and biology in intervertebral disc degeneration: a vicious circle

Objective
Degenerative intervertebral disc disease is common; however, the importance of genetic factors is unknown. This study sought to determine the extent of genetic influences on disc degeneration by classic twin study methods using magnetic resonance imaging (MRI).

Methods
We compared MRI features of degenerative disc disease in the cervical and lumbar spine of 172 monozygotic and 154 dizygotic twins (mean age 51.7 and 54.4, respectively) who were unselected for back pain or disc disease. An overall score for disc degeneration was calculated as the sum of the grades for disc height, bulge, osteophytosis, and signal intensity at each level. A “severe disease” score (excluding minor grades) and an “extent of disease” score (number of levels affected) were also calculated.

Results
For the overall score, heritability was 74% (95% confidence interval [95% CI] 64–81%) at the lumbar spine and 73% (95% CI 64–80%) at the cervical spine. For “severe disease,” heritability was 64% and 79% at the lumbar and cervical spine, respectively, and for “extent of disease,” heritability was 63% and 63%, respectively. These results were adjusted for age, weight, height, smoking, occupational manual work, and exercise. Examination of individual features revealed that disc height and bulge were highly heritable at both sites, and osteophytes were heritable in the lumbar spine.

Conclusion
These results suggest an important genetic influence on variation in intervertebral disc degeneration. However, variation in disc signal is largely influenced by environmental factors shared by twins. The use of MRI scans to determine the phenotype in family and population studies should allow a better understanding of disease mechanisms and the identification of the genes involved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28199902%2942%3A2%3C366%3A%3AAID-ANR20%3E3.0.CO%3B2-6

Genetic influences on cervical and lumbar disc degeneration: A magnetic resonance imaging study in twins

Study Design. A new technique to measure the viscoelastic behavior of the nucleus pulposus in shear was used to assess its solid and fluid characteristics. Objectives. To review existing knowledge on mechanical behaviors of the nucleus pulposus, and to develop a new technique to study the viscoelastic behaviors of isolated nucleus pulposus samples in torsional (pure) shear under transient and dynamic conditions. Summary of Background Data. Numerous studies have investigated the swelling behavior of the nucleus and found the swelling pressure to range approximately 0.05-3 MPa, depending on loading conditions. Very few studies, however, have investigated the load-deformational behaviors of the nucleus pulposus. Methods. Thirteen nondegenerate samples of nucleus pulposus were harvested from lumbar discs and tested in torsional shear under tansient and dynamic test conditions. A linear viscoelastic law with variable amplitude relaxation spectrum was used to model the stress relaxation and dynamic frequency sweep experiments. The coefficients of the viscoelastic law were determined from the stress relaxation experiments, whereas the dynamic shear modulus and phase shifts angle were determined from the frequency sweep. Results. The nucleus exhibits significant viscoelastic effects in shear. Under transient conditions, the stress relaxed to values near zero, which is indicative of the fluid-like behaviors of the nucleus. Under dynamic conditions, however, the material parameters for the nucleus, magnitude of the complex modulus (7-21 kPa), and phase angle (23-31°) were more characteristic of a viscoelastic solid. The authors' proposed stress-strain law exhibited excellent agreement with the viscoelastic data. Conclusions. In response to shear deformations, the nucleus pulposus exhibited significant viscoelastic effects, characteristic of a fluid and a solid. Whether the nucleus pulposus behaves more as a fluid or a solid in vivo depends on the rate of loading.

Is the nucleus pulposus a solid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc.

Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression

Study DesignThe structure-function relationship of anulus fibrosus of nondegenerate lumba intervertebral discs was investigated.ObjectivesThe tensile properties and biochemical composition of single lamella specimens from human anulus librosus and their variations with anatomic region were determine

Regional variation in tensile properties and biochemical composition of the human lumbar anulus fibrosus

Study Design. Samples of human lumbar (L3-L4) anulus fibrosus from four different anatomic sites (anterior outer, posterolateral outer, anterior inner, posterolateral inner), ranging fom normal to severely degenerate, were studied in uniaxial tension and measured for water content. Objectives. To evaluate the effects of agning and degeneration on the tensile properties and hydration of the anulus fibrosus in a site-specific manner. The relationship between hydration and parameters of the tensile behavior were investigated. Summary of Background Data. Degeneration and aging have been shown to be related to dramatic changes in the composition and structure of the anulus fibrosus. The associated changes in the tensile, comppressive, and shear properties of the anulus fibrosus have not been documented. Numerical studies using finite element models have attempted to simulate the degenerative process by incorporating estimated mechanical properties meant to represent the degenerate anulus fibrosus. their results present findings that suggest that altered material properties of teh anulus fibrosus affect the mechanics of the entire intervertebral disc. Methods. Samples of human lumbar anulus fibrosus were classified by grade of degeneration based on a morphologic grading scheme. Multiple layer anulus specimens from four sites in the disc were tested in uniaxial tension under quasistatic conditions in a physiologic saline bath. The tensile modulus, poisson's ratio, failure stress and strain, the strain energy density to failure, and the corresponding hydration were determined for each test sample. Results. The Poisson's ratio, failure stress, and strain energy density of the anulus fibrosus were found to be affected significantly by degeneration, with some evidence fo a sensitivity of the tensile modulus to grade of degeneration. All material properties were found to exhibit a significant and greater dependence on site within the disc than on degenerative grade. Weak correlations between aging and the poisson's ratio and strain energy density were observed. Water content of anulus fibrosus tissue was not affected by degeneration or aging, although correlations with tensile properties were observed. Conclusions. The dramatic changes in morphology, composition, and structure that occur in anulus fibrosus with aging and degeneration are accompanied by specific variations in the tensile properties, which were generally small in magnitude. position of the anulus fibrosus within the intervertebral disc, particularly in the radial direction, appeared to be the most important variable affecting anulus fibrosus tensile porperties. This dependence on position did not change with either agning or degeneration. Results from the present study may be useful in future finite element models to assess how altered material properties of the anulus fibrosus during degeneration and aging may affect the mechanics of the entire intervertebral disc

Degeneration and Aging Affect the Tensile Behavior of Human Lumbar Anulus Fibrosus

Study Design The in vitro tensile behavior of multiple-layer samples of anulus fibrosus were investigated from nondegenerate intervertebral discs. Objectives To quantify the intrinsic tensile behavior of nondegenerate anulus fibrosus and the variations with position and age in the intervertebral disc. Summary of Background Data Tension is an important loading mode in the anulus fibrosus. The tensile behavior of single- and multiple-layer samples of anulus fibrosus has been shown to vary with specimen orientation, position in the disc, and environmental conditions. Little is known of the changes in these site-specific tensile properties of the anulus with aging or degeneration of the intervertebral disc. Methods Multiple-layer specimens of anulus fibrosus were harvested with an orientation parallel to the circumference of the disc. Constant strain rate and uniaxial tensile tests were performed in 0.15 mol/l NaCl at slow strain rates to measure the intrinsic properties of the collagen-proteoglycan matrix of the anulus fibrosus. The tensile modulus, failure stress, failure strain, and strain energy density were determined. Statistical analyses were done to evaluate regional and age-related differences in these properties. Results Significant radial and circumferential variations in the intrinsic tensile properties of anular samples were detected. The anterior anulus fibrosus had larger values for tensile moduli and failure stresses than the posterolateral anulus. Also, the outer regions of the anulus had greater moduli and failure stresses and lower failure strains than the inner regions. Strain energy density did not vary significantly with region. Significant, but very weak, correlations were detected between tensile properties and age of the intervertebral disc. Conclusions The observed variations in tensile behavior of multiple-layer anulus samples indicate that larger variations in tensile modulus and failure properties occur with radial position in the disc than from anterior to posterolateral regions. This pattern is likely related to site-specific variations in the tensile properties of the single-layer samples of anulus fibrosus lamellae and the organization of successive lamellae and their interactions. The results of the present study suggest that factors other than age, such as compositional and structural variations in the disc, are the most important determinants of tensile behavior of the anulus fibrosus.

Mark Weidenbaum

Papers

Is the nucleus pulposus a solid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc.

Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression

Regional variation in tensile properties and biochemical composition of the human lumbar anulus fibrosus

Degeneration and Aging Affect the Tensile Behavior of Human Lumbar Anulus Fibrosus

Tensile properties of nondegenerate human lumbar anulus fibrosus