LUMBAR INTERVERTEBRAL DISC.

A FASCINATING STRUCTURE

International Publicized Data

GMCD Instructional Course Lectures

Author :  

Dr. med. Guy M.C. Declerck MD (GMCD)

Medical FRCS-, FRCS Ed Orth-, M Ch Orth-, PhD-studies

Spinal Surgical and Research Fellow, Perth, Western Australia

Spinal Orthopaedic Surgeon and Surgical Instructor

Consultant R&D Innovative & Restorative Spinal Technologies

President International Association of Andullation Technology (IAAT)

Copywriter / Translator:   Filip Vanhaecke PhD

Illustrative expertise: Lennart Benoot, Mincko, Halle and Natacha Monstrey, HHP, Flanders, Belgium

Artistic illustrations: Alonso Ríos Vanegas, sculptor and writer, Medellín, Colombia

Page layout:   Lennart Benoot, Mincko, Halle, Flanders, Belgium

Review scientific literature:   Medical Consulting Advice, Ostend, Flanders, Belgium

Support:   International Association of Andullation Therapy (IAAT)

Legal advice:   Anthony De Zutter, kornukopia.be

Dedication to Gloria Rúa Meneses. February 2014. 

I tried to learn your name once.

You scowled, unaware of the favor I’d done you.

My interval expired. I’ve seen it from every angle now.

Each time, I came closer to doing what must be done.

Each time? I wonder how long they’ll let me do this.

Or maybe I’ll just keep going, on and on, until I decide I’m done.

Acknowledgements

Relying on the work of giants is the lifeblood of scientific research. Indeed, if I have seen further, it is by standing on the shoulders of giants. One might even say that I have always depended

on the kindness of strangers in this regard (*).

The continuous support by professor BA Kakulas (Neuropathology), professor JR Taylor (Spinal Anatomy and Human Biology), and Sir George M Bedbrook (Spinal Orthopaedic and Rehabilitation Surgeon)

made it possible to analyse 23539 post-mortem human spines, normal and pathological, in the Department of Neuropathology, Royal Perth Hospital/University Western Australia, Perth.

Note: in order not to disturb easy reading of the underneath scientifically based chapters, only a few authors are mentioned in the text where dr. Guy considered it essential.

Their names are placed between brackets. Further information on their individual research can be read in the last chapter ‘Literature Encyclopedia’.

(*) Mirsky Steve. Technology is making it harder for word thieves to earn outrageous fortunes. Scientific American, February 2014, p. 64

Table of contents

1. The need for understanding the structure of the lumbar intervertebral disc

2. Intervertebral discs are avascular, aneural, and paucicellular

3. Intervertebral discs and the length of the spinal column

4. Lumbar intervertebral discs fulfil very demanding functional tasks

5. Lumbar intervertebral discs are extraordinary entities and no simply cushions

6. The healthy lumbar intervertebral disc consists of three anatomical zones

7. Embryogenetic origin of the three distinct anatomical intervertebral disc zones

8. Endplates: structure and function

9. Endplates: elastic properties

10. Endplates: microfractures, clefts, fissures and tears precipitate the disc to degenerate

11. Endplates: traumatic lesions precipitate the disc to degenerate

12. Endplates during the osteoporotic aging processes

13. Nucleus pulposus: composition

14. Healthy nucleus pulposus: function

15. Degenerative nucleus pulposus: function

16. Annulus fibrosus: structural organisation

17. Annulus fibrosus: inner part differs from the outer part

18. Annulus fibrosus: attachment to the endplates

19. Annulus fibrosus: function and lesions

20. Literature Encyclopaedia

1. Need for understanding the lumbar intervertebral disc

Detailing the well-designed anatomical structure of the lumbar intervertebral disc (IVD), consisting of endplates (EP), nucleus pulposus (NP), and annulus fibrosus (AF), implicates an interest in trying to understand the mechanical function of the lumbar IVDs as well as the reasons why these IVDs may cause pain. This knowledge is essential for developing innovative and effective biological treatments.

The normal and healthy lumbar IVD has a very high water content. Before the age of 20 years the central nucleus pulposus (NP) consists of approximately 80 % water and the peripheral annulus fibrosus (AF) contains up to 60 % water (Fig. 1a).

Fig. 1a. X83-478. The normal L4-L5 lumbar intervertebral disc in a one-day old male individual is fully hydrated. The central nucleus pulposus (NP) consists of approximately 80 % water. The peripheral annulus fibrosus (AF) contains up to 60 % water.

(Left: X83-478, Declerck / Kakulas, Neuropathology, Perth, Western Australia)

(Right: detailed illustration of X83-478 by Colombian Sculptor Alonso Ríos, www.alonsoriosescultor.com)

When the initial high intradiscal concentration of water-attracting and water-binding proteoglycans in the NP starts decreasing, the IVD begins losing its aqueous appearance (Fig. 1b).

 

Fig. 1b. X89-1450. An accident in a 22-year old individual caused the posterior annulus fibrosus of the L4-L5 intervertebral disc to rupture (a typical traumatic out-to-in fissure). The nucleus pulposus of the otherwise normal L4-L5 lumbar intervertebral disc is highly hydrated. Before the accident, the hydrostatic loadings and swelling pressures in the nucleus pulposus during the daily activities could be resisted by a resulting tension resistance in the annulus fibrosus because its intact type I collagen content. This explains why the intervertebral disc height is still maintained.

(Left: X83-1450, Declerck / Kakulas, Neuropathology, Perth, Western Australia)

(Right: detailed illustration of X83-1450 by Colombian Sculptor Alonso Ríos, www.alonsoriosescultor.com)

In normal circumstances, any compressive load applied to a healthy IVD is carried by a balance between the elicited hydrostatic loading in the gel-like NP and the resulting tensile resistance of the annular wall caused by the intact type I collagens. In other words, any hydrostatic swelling pressure in the NP is resisted by a resulting tension in the AF. Consequently, this annular tension is responsible as well for maintaining the normal distance between the adjacent vertebral bodies.

Aging processes change the micro- and macrostructure of the NP, the AF and the endplates in the IVD. The capacity to attract and bind water gradually decreases. This dehydration leads to - painless - internal ruptures of the NP. But when structural failures such as fissures and tears arise in the endplates and / or AF, the IVD starts degenerating (Fig. 1c).

From clinical perspective, the degenerative fissures and tears may become the source of potential discogenic dysfunction and pain. Decreasing IVD height, herniating pathways, intervertebral hypermobility, spondylolisthesis and spinal stenosis are the irrefutable degenerative consequences.

Interesting note. Explorative experiments which eventually will lead to innovative biologic therapeutic approaches cannot be performed on humans for ethical reasons. Therefore, lumbar IVDs of sheep are used for analysis of the evolving degenerative processes. And because calfs possess lumbar IVDs with similar size, shape, and structure similar to the human lumbar IVD, the spinal flexibility of the calf spine shows similarities with human IVDs. Consequently, the results of the biochemical and biomechanical investigations on sheep and calf IVDs indirectly improve the insight in the mechanobiology of the human lumbar IVDs.

Fig. 1c. The intervertebral disc ages. Left: the endplates (EP) and the outer annulus fibrosus (AF) in the healthy and young IVDs are vascularized. The NP always remains without blood supply. The young NP contains a high concentration of proteoglycans and water (80 %). Right: in the adult IVD, the EPs become calcified and ossified and all blood vessels occlude. The outer AF becomes more and more avascular. In the NP, the proteoglycans disintegrate, attract and bind much less water. The NP changes its gelatinous structure to a progressing more disrupted and fibrous tissue. The AF starts bulging into the NP. Note that the AF has a laminated expression.

2. Intervertebral discs: avascular, aneural, and paucicellular

In contrast to any other organ in the human body and with the exception of the outermost third of the AF, the mature lumbar IVDs contain no blood vessels, no nerves, and only a small amount of cells (only 1 % of the adult nuclear disc tissue). However, the IVD still has to fulfil amazing functional biomechanical tasks.

3. Intervertebral discs and spinal column length

Human spines normally possess 23 intervertebral discs. The IVDs are responsible for approximately 20 % to 30 % of the length of the spinal column. When astronauts, cosmonauts, or taikonauts no longer are subjected to the Earth’s gravitational forces, their IVDs - and depending on the remaining concentration of proteoglycans - refill with water and increase the hydrostatic pressure in the central nuclei pulposi causing an increase of the spinal length.

On the other hand, all human beings older than 50 years of age experience a decreasing length of the vertebral column due to both the progressing osteoporotic processes in the vertebrae and the degenerative processes in the IVDs. If osteoporotic vertebral compression fractures are delayed, the decrease is due to the narrowing of the IVD heights.

4. Lumbar intervertebral discs fulfil demanding tasks

The lumbar IVDs act as the most important joints in the spinal column (besides the zygapophyseal facetal joints). In the standing ‘rest’ position, i.e. while waiting in line for a bus, healthy and non-degenerated IVDs bear 80 kg per cm² disc tissue. This equals the weight of eight cases with 24 fully filled bottles of beer. The weight per cm² disc in a slight 10° flexion increases to an equivalent of 210 kg or 21 cases of beer. And if loaded, the IVDs bear at least 350 kg per cm².

In a normal, healthy and non-degenerative IVD, the endplates, nucleus pulposus, and the annulus fibrosus absorb all loads from body weight, daily activities, and muscle tension. A perfect interaction between the three structures results in an even distribution of the loads to the lumbar vertebral bodies. These mechanical mechanisms facilitate but restrict the complex and multi-axial spinal motions. As such, the IVDs are responsible for the flexibility and stability of the spine.

From clinical point of view, inadequate and asymmetrical load transmission patterns through the IVD may induce pain (Mulholland).

5. Lumbar intervertebral discs are no simply cushions

The lumbar IVDs are amazing and fascinating structures. In contrast to what is taught, written and generally thought, lumbar IVDs are not at all ordinary soft and ‘simple’ cartilaginous cushions anchoring two adjacent vertebral bodies. IVDs require a heterogenous but exceptionally well-designed structural organisation to meet important mechanical demands.

6. Healthy lumbar intervertebral: three anatomical zones

In the healthy and non-degenerated IVD, three distinct but highly coupled fibrocartilaginous anatomical zones can be distinguished. The inner structure, the nucleus pulposus (NP), is surrounded by a firm and much better organized collagenous outer ring termed the annulus fibrosus (AF). Both inferior and superior outer limits of the IVD, named the endplates (EP), separate the NP from the adjacent vertebral bodies (Fig. 6a).

In each of the three structures (NP, AF and EP) sparse cells respond to the daily load patterns by continuously breaking down and synthesizing their extracellular matrix. Indeed, the IVD continuously undergoes micro- and macroscopic changes. However, during the progressing degenerative stages, Mother Nature produces more and more collagen fibers (especially type I) so that the entire IVD gradually fibroses (Fig. 6b). In the end, the integrity of the three regions (NP, EP, AF) is completely lost and it becomes completely impossible to distinguish one zone from the other (Fig. 6c).

Fig. 6a. A70/355 (male - 70 years old). The aging L1-L2 intervertebral disc shows a slightly decreased disc height. Intact endplates (EP) separate the aging and brown coloured central nucleus pulposus (NP) from both vertebral bodies. At its periphery, the NP is surrounded by an aging annulus fibrosus (AF). The anterior collagenous lamellae bulge outwards but posteriorly the most inner collagenous layers start folding inwards. Degenerative internal nuclear ruptures are as yet not present. Degenerative endplate fissures are absent. Note: the laminated structure of the AF is clearly visible.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 6b. A90/139 (male aged 50 years). A normal aging L3-L4 intervertebral disc (IVD) without degenerative characteristics. The central nucleus pulposus (NP) has the typical aging ‘brown’ colour, the endplates remain well delineated and the parallel oriented laminated sheets in the annulus fibrosus (AF) are clearly visible. The L4-L5 disc shows the advanced stages of disc degeneration. The brown NP is internally disrupted. The NP no longer can be distinguished from the AF which anteriorly is ruptured allowing degenerative nuclear material to ‘herniate’. The inferior L4 endplate is interrupted. Through these fissures the degradative (inflammatory) nuclear products migrate into the L4 vertebral body where they create discolouration in the subchondral bone (compatible with Modic changes on MRI). At the level of the L5-S1 IVD, the posterior AF is ruptured with subsequent protrusion, resorption and disc height loss. Posterior parts of the endplates (EPs) are resorbed. Through the EP fissures degradative products migrate into the posterior subchondral bone and cause the intraosseous light brown discoloration. The laminated structure in the AF is clearly visible.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 6c. X89/859 (male 70 years). Fully degenerated and already resorbed L5-S1 intervertebral disc (IVD). The endplates are completely destroyed. Inflammatory osseous reactions are seen all over in the subchondral bone of the L5 and S1 vertebrae (white discolouration). The healing processes, orchestrated by Mother Nature, spontaneously fuse both vertebrae to each other: the natural history of a degenerating IVD!

Note: the yellow spot in the L5 vertebra underneath the aging (but as yet not degenerating) L4-L5 IVD represents fat related to the fatty disintegration of osteoblastic bone forming cells.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

7. Embryogenetic origin of IV discs: essentials

In the very early stages of human embryonic development, a complex process called the ‘gastrulation’ differentiates a single layer of identical embryonic stem cells into three germ cell layers. These three distinctive zones - the endoderm, mesoderm and exoderm - finally form all organs.

The central and para-axial parts of the mesoderm form the three distinct anatomical zones of the IVD (Choi; McCann; Sivakamasundari).

The central mesoderm forms a rod-like structure termed the notochord. Its notochordal cells give rise to the central nucleus pulposus (NP). However, the notochordal cells are not able to respond to mechanical loads exerted on them. Once the infant starts putting more and more weight onto his spine around the age of 8 years (sitting, standing, walking, running, etc …) most notochordal cells will stop their normal metabolic activities. They no longer will synthesize the essential water-binding proteoglycans. While the NP further develops into a mature weight-bearing structure, some notochordal cells have no choice but transforming into chondrocytic-like cells which are essential for synthesizing the necessary collagen fibers (type II) to resist the compressive load-bearing activities. Some other notochordal cells become afunctional and express a large vacuolisation. The initially clear and translucent NP liquid, which may exist for 80 % of water molecules, disappears to become more opaque and more viscous. For these reasons, the disappearance and decreasing number of original notochordal cells in the NP are regarded as a loss of regeneration potential of the IVD. Indeed, the aging processes in the IVD already start in the early teenage years.

The para-axial mesoderm gives rise to sclerotomal cells. They condense around the notochord and will form the annulus fibrosus and the cartilaginous endplates.

8. Endplates: structure and function

The endplates (EP), derived from the para-axial mesoderm, are 0,6 to 1 mm thick and consist of both an osseous and a cartilaginous layer (Fig. 8a and 8b). The bony layer represents the superior and the inferior cortical coatings of the vertebral body (VB). It contains multiple openings through which nutrition of the IVD is facilitated. The cartilaginous layer (collagen type II fibers and chondrocytic-like cells) forms the shelf-like floor and ceiling of the IVD separating the nucleus pulposus (NP) from the adjacent VBs. It regulates the diffusion of water from the NP through the bony EP into the VB and vice versa, depending on the loading conditions.

Indeed, intact EPs serve as the main route for metabolites in and out of the IVD tissue in the NP. The endplates are essential for the maintenance the nuclear hydrostatic pressure required for the normal biomechanical function of the IVD.

With advancing age, both EPs undergo mineralisation, calcification and final ossification. The irreversible age-related processes progressively occlude the openings in the bony layer of the EP. Once the EPs become impermeable, diffusion of water and supply of nutrients become impossible, and metabolic waste products start to accumulate in the nucleus pulposus.

Fig. 8a. A83/85 (female - 60 years). Superior endplate - thickness: 0,6 to 1mm - in an aging L5-S1 IVD.

Note the laminated structure in the annulus fibrosus.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 8b. A70/355 (male 70 years). Inferior endplate – thickness: 0,6 to 1 mm – in an aging L1-L2 IVD.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

9. Endplates: elastic properties

The EPs always remain the weakest parts of the lumbar intervertebral disc. The weakest part is localized in the central area (0,6 mm). Initially, EPs are very resilient during normal compressive loading of the spine. During experimental loading sets, the EPs bulge approximately 0,25 mm into the adjacent vertebral bodies. This mechanism prevents the EPs for being damaged during normal daily activities and hinders the nucleus pulposus to protrude into the vertebral bone tissue.

10. Endplates: microfractures, clefts, fissures and tears precipitate degenerative processes

Because the mechanical resilience of the EPs decreases during the aging processes of cartilage and bone (from the age of 30 years), structural changes in the EPs will arise as well. Compressive endplate lesions mostly develop during normal daily compressive loading activities such as standing, sitting, bending, and stretching.

Microfractures, clefts, fissures and tears develop in the EPs at all lumbar IVD levels (Fig. 10a and Fig. 10b). In the L1-2 and L2-L3 IVDs, endplate lesions usually occur before ruptures in the annulus. The EP lesions cause acute episodes of low back pain and are the major factors for initiating or stimulating the degenerative processes in the nucleus pulposus. This evolution may lead to the generation a chronic degenerative discogenic syndrome (DDS).

Initial small-scale degenerative EP lesions still remain undetectable radiologically. However, magnetic resonance imaging (MRI) may express evolving and sometimes disappearing signal intensity changes in the adjacent subchondral zones of the vertebral bone marrow. On the MRI these changes are described as the so-called Modic reactive changes.

Fig. 10a. X90/1063 (female 40 years of age). Classic example of the degenerative involution of intervertebral discs. The normally occurring microfractures, fissures and tears in the superior endplates are clearly seen at the L2-L3 and L3-L4 intervertebral disc levels.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 10b. A90/149 (male aged 79 years). The superior endplates of the L3-L4 and L4-L5 intervertebral discs  show more destructive lesions than the inferior endplates. Consequently, more reactive (inflammatory) bone marrow changes are seen in the subchondral bone above the superior endplates (compatible with MRI Modic type changes).

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

11. Endplates: traumatic lesions precipitate disc degeneration

Because the cartilaginous and the bony EPs are weakly bound to each other, spinal injuries in youngsters, e.g. hyperflexion and hyperextension injuries during skiing or judo, may result in the avulsion of the intervertebral disc from the vertebral body (Fig. 11a).

Spinal accidents which damage parts of the EP or (temporarily) separate the EP from the vertebral body, inevitably lead to early aging and degeneration of the IVD. The remaining openings in the osseous endplate eventually will occlude and interrupt the precarious nutrition of the nucleus pulposus (Fig. 11b). In some instances, nuclear material may herniate into the vertebral marrow forming a Schmörl’s-like nodule when the nuclear tissue becomes calcified (Fig. 11c).

Fig. 11a. X89/676 (male aged 9 years). Avulsion of the L1-L2 intervertebral disc from the L2 vertebral body. The separation between cartilaginous and osseous parts of the superior L2 endplate is evident.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 11b. A90/139 (male 62 years). The aging T12-L1 intervertebral disc shows the typical brown discoloured nucleus pulposus (NP). Except for a small fissure in the NP (black spot), no ruptures are visualized in the endplates nor in the annulus fibrosus (AF). At the L1-L2 disc level, the anterior part of the superior endplate has been destroyed during an accident and is no longer visible. In the adjacent subchondral bone of the L1 vertebral body, light brown discolouration is visible. Underneath the endplate, a large degenerative tear developed in the anterior AF (initiated by the accident?) and extends into the NP.

Note: the laminated structure in the AF is clearly seen.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 11c. A90/76 (male aged 67 years). Old inferior endplate fracture with migration of nuclear material into

the vertebral body. Over time when the herniated nuclear material becomes surrounded by a calcified layer, this lesion becomes visible on radiological images as a Schmorl nodule. The intervertebral disc is degenerated. The laminated structure of the annulus fibrosus is evident. Note: metastatic lesions are present in the subchondral bone and do not invade the endplates.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

12. Endplates during the osteoporotic aging processes

The osteoporotic aging processes which initially resorb more horizontal osseous trabeculae but gradually produce more microfractures in the vertical trabeculae as well, allow the NP to gradually bulge more and more into the weaker vertebral cancellous bone tissue. The protruding progression of the IVD eventually leads to the formation of the typical radiologically thick and biconcave discogenic deformation. On radiological evaluations, these IVDs are incorrectly described as ‘normal’ although all IVDs show at least the aging processes primarily expressed by the typical brown discolouration of the NP (Fig. 12a and Fig. 12b).

Fig. 12a. X90/1442 and Fig. 12b. X90/1437. Routine findings in an osteoporotic spine indicating the progressive biconcave protrusion of intervertebral discs (IVD) into the osteoporotic vertebral bodies. Note that the disc height of all IVDs is still normal. Although no degenerative lesions are present, all IVDs show the brown discolouration of the nucleus pulposus expressing the aging processes. The laminated structure in the annulus fibrosus remains evident.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

13. Nucleus pulposus: composition

The NP is the inner but eccentrically localized component of the IVD and forms an irregular three-dimensional scaffold of randomly oriented fibrous strings. The strings consist of collagen and some elastin fibers.

In the healthy and non-degenerated IVD, the scaffold contains a soft and highly hydrated gelatinous material. The gel is made of a mixture of water and extracellular matrix (ECM). The chondrocytic-like cells which synthesize and maintain the ECM account for only 1 % of the adult nuclear disc tissue. The mature NP contains very few fibrocytes as well but less than in the annulus fibrosus. The ECM consists of type II collagen and proteoglycan aggrecan in a ratio of 1 : 20 (cf. articular cartilage in the large joint 1 : 2). The abundant large aggregates of proteoglycans are responsible for attracting and retaining water. In molecular terms this means that one proteoglycan molecule holds 500 water molecules. The water content in the young NP ranges from 60 % to 80 % (Fig. 13).

Fig. 13. X83/478 (teen L4-L5 intervertebral disc). The extraordinary functions of the intervertebral disc are by all times explained by its molecular consistency.The young nucleus pulposus (NP) can contain up to 80 % water. Its extracellular matrix is made up of approximately 15 % proteoglycans, 4 % collagen type II fibers and 1 % elastin fibers. In  contrast, the young annulus fibrosus (AF) consists of 80 % collagen type I fibers and only 20 % water. Therefore, the NP is responsible for distributing compressive load to the AF and the AF is constructed to resist tension forces.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

14. Healthy and normal nucleus pulposus: function

A normal NP can fill 30 % to 50 % of the total IVD cross sectional area. The healthy NP bears the majority of the tremendous weight of the body called axial load. Indeed, the NP is a good functioning composite structure. The collagenous scaffold imparts compressive strength and the proteoglycan gel binds water making the nucleus deformable.

Because of its high water content and low rigidity, the NP is a hydrostatic environment (Fig. 14a and Fig. 14b). Biomechanically it behaves like a fluid under pressure. During normal daily loading conditions (mostly compression and/or flexion) the hydrostatic pressure in the NP increases. As fluid cannot be compressed, the loads are uniformly redistributed in all directions during all movements of the spine. Due to this so-called isotropic behaviour of the NP, compressive loads on the spine and on the IVDs generate tensile stresses in the annulus fibrosus. This results in the AF continuously undergoing varying stress concentrations.

A healthy NP provides the IVD with resistance to compressive deformations. Indeed, a well-functioning IVD can be compared with the behavior of a normal car tire.

Fig. 14a and Fig 14b. Normal aging intervertebral discs (IVD) which still express sufficient hydrostatic pressure. Because no degenerative changes are present in the nucleus pulposus, endplates or annulus fibrosus, the IVD functions like normal car tires. The laminated structure in the annulus fibrosus remains visible.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

15. Degenerative nucleus pulposus: function

The aging processes in the lumbar IVDs are initiated by a decreasing concentration of proteoglycans leading to loss of water content and resulting in a decrease of hydrostatic pressure. These changes alter the local distribution of the loads onto the IVDs and finally start disrupting the disc tissues causing degenerative erosions, fissures and tears (Fig. 15). At the upper lumbar L1-L2 and L2-3 levels, the depressurisation is rather associated with degenerative endplate erosions. At the lower lumbar levels, the decrease in nuclear pressure leads to the transmission of higher compression loads and an increased concentration of compressive stress into the posterior portions of the annulus fibrosus. Indeed, the prevalence of degenerative annular fissures and tears is much higher at the L4-L5 and L5-S1 disc levels.

The degenerative processes in the IVD can be compared to the behavior of a flat tire. Decompression of the NP results in disc narrowing and gradually more compressive load transfer to the annulus (up to more than 50%). The outer part of the annulus starts bulging outward but its inner part collapses inward.

 

Fig. 15. X90/1063. Lumbar spine (L1-L2, L2-L3, L3-L4, L4-L5 IVDs) of a 40 year old male. He never presented severe and disabling low back pain episodes but of course complained of some low back trouble. Because of the macroscopic destruction of the nucleus pulposus (NP), endplates and annulus fibrosus (AF), the IVDs no longer are able to resist the compressive (especially by the NP) and tensile (especially by the AF) deformative loads. Indeed, the evolving abnormal loading distribution can induce low back complaints (Mulholland) and may lead to a painful degenerative discogenic syndrome.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

16. Annulus fibrosus: structural organisation

The embryonic para-axial mesoderm gives rise to the AF. It is the firm but highly organized laminated collagenous outer ring which surrounds each nucleus pulposus (Fig. 6a, 6b, 8A, 11b, 11c, 14a and 14b).  The AF is build up of 15 to 25 nearly fully concentric (not 360°!) and more or less parallel oriented sheets, called lamellae (Fig. 16a, Fig. 16b and Fig. 16c). In each of these lamellae, bundles of collagen fibers are oriented parallel to one another and run obliquely between the vertebral bodies at angles of 30 degrees with respect to the horizontal plane of the endplates (see Function of AF and Fig. 19a). However, the collagen bundles in each layer run in opposite directions with the fibers in one annular layer directed to the right and those in the immediate adjacent layers to the left. This particular selective orientation is a prerequisite for the AF to sustain high tension loads and resist torsional damage.

Contrary to the NP, the approximately 60 % water content in the AF remains relatively constant with age. The tissue of the AF contains more fibrocytes but less chondrocytic-like cells than the nucleus pulposus.

 

Fig. 16a. A82/132 (male - 80 years), 16b. X83/593 (male - 57 years) and 16c. Architecture of the annulus  fibrosus. Some 15 to 25 collagenous lamellar sheets surround the nucleus pulposus.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

Fig. 16b. Sagittal section through the intervertebral disc of a sow (Sus scrofa domesticus). The lamellae in the collagenous outer annular ring around the nucleus are clearly visible (authorization by the Dierengezondheidszorg, Flanders, Belgium).

17. Annulus fibrosus: difference between inner and outer collagenous layers

The outer lamellar zone of the AF is less deformable than the inner zone. From the interior outward, the amount of type II collagen fibers decreases whereas that of type I collagens increases (Fig. 17). The more softer inner lamellar layers of the AF, which gradually merge with the NP, consist of 70 % fine type II collagen fibers. A healthy gelatinous NP only contains 4 % collagen type II fibers. The type II collagen fibers in the inner zone of the AF, like those in the NP, are minimally interconnected by other smaller molecules. In the tougher outer lamellae, the collagen bundles comprise 90 % type I collagen fibers and only 10 % proteoglycans. The collagen type I fibers are well cross-bridged by smaller molecules like elastin and collagens type V, VI and XI.

IVD structure

Collagen fibers

Consistence

Healthy nucleus pulposus

  4 % type II – no type I

gelatinous

Inner annulus fibrosus

70 % type II

soft

Outer annulus fibrosus

90 % type I – no type II

tough and rigid

Fig. 17. The average percentages of collagen fibers (based on data in the literature) in the nucleus pulposus

and annulus fibrosus express their consistency.

18. Annulus fibrosus: attachment to the endplates

The type II collagenous lamellae of the inner annular layers are loosely attached to the cartilaginous zone of the endplates. Avulsions of the nucleus pulposus at this level are frequent undiagnosed traumatic lesions in youngsters.

The collagen type I fibers in the outer and more tougher part of the AF are powerfully attached to the peripheral area of the osseous endplate (through the Sharpey’s fibers) but do not enter the subchondral bone. This particular insertion place of outer collagen type I fibers, called the ring apophysis is a common site for peripheral rim fractures and tears (Fig. 18).

Fig. 18. Male - 19 years old – reference 896441. Rim avulsion at the L4-L5 disc level (confirmed at surgery).

19. Annulus fibrosus: function and lesions

The strength of the AF is proportional to both its type I collagen content and its characteristic cross-woven structural orientation of the lamellae (Fig. 16a, 16b and 16c).

Although its tough, rigid, and less deformable outer zone, a healthy AF remains flexible before mechanical failure may occur. The type I collagen bundles in each of the successive laminae run at an angle of 120° to those in the two immediately adjacent sheets (Fig. 19a). This explains why during torsional motions of the lumbar spine, only 50 % of fibers are put into tension while the other 50% become slack (Fig. 19b). This highly specialised structural orientation provides strength to high tensile loading and resistance to torsional damage and distension. With age, the AF loses strength and pliability which make it gradually more susceptible to the development of traumatic and degenerative tears in the inner zone, the occurrence of more annular bulgings (especially at the L4-5 and L5-S1 intervertebral disc levels), and the development of herniating pathways (protrusion, extrusion, and sequestration).

   

Fig. 19a. Left. In each of the lamellae, bundles of collagen fibers are oriented parallel to one another and run obliquely between the vertebral bodies at angles of 30 degrees with respect to the horizontal plane of the endplates. The type I collagen bundles in each of the successive laminae run at an angle of 120° to those in the immediately adjacent sheets.

Fig. 19b. Right. During torsional motions of the lumbar spine, only 50 % of collagen fibers are put into tension (represented by the elongated and more horizontal oriented blue lines) while the other 50 % become slack (represented by the shorter more vertical orientated blue lines).

20. Literature Encyclopaedia

A

Adams MA

Personal communications

Spine Society of Europe. Spine Course 2006. Chronic low back pain

Spine Course, September 2006, Barcelona, Spain

Adams MA, Bogduk N, Burton K, Dolan P

The biomechanics of back pain (2nd ed)

Churchill Livingstone, Edinburgh, 2006

Adams MA, Dolan P

        Intervertebral disc degeneration. Evidence for two distinct phenotypes

        J Anat, 2012, 221:497

Adams MA, Dolan P, Hutton WC

The lumbar spine in backward bending

Spine, 1988, 13:1019

Adams MA, Dolan P, Hutton WC

The stages of disc degeneration as revealed by discograms

J Bone Joint Surg, 1986, 68B:36

Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P

Mechanical initiation of intervertebral disc degeneration

Spine, 2000, 25:1625

Adams MA, Green TP

Tensile properties of the annulus fibrosus. I. The contribution of fibre-matrix interactions to tensile stiffness and strength

Eur Spine J, 1993, 2:203

Adams MA, Hutton WC

Prolapsed intervertebral disc. A hyperflexion Injury. 1981 Volvo award in basic science.

Spine, 1982, 7:184

Adams MA, Hutton WC

The effect of posture on diffusion into lumbar intervertebral discs

J Anat, 1986, 147:121

Adams MA, Hutton WC

The effect of posture on the fluid content of lumbar intervertebral discs

Spine, 1983, 8:665

Adams MA, Hutton WC

The mechanical function of the lumbar apophyseal joints

Spine, 1983, 8:327

Adams MA, McNally DS, Dolan P

'Stress' distributions inside intervertebral discs. The effects of age and degeneration

J Bone Joint Surg, 1996, 78B:965

Adams MA, Roughley PJ

What is intervertebral disc degeneration, and what causes it?

Spine, 2006, 31:2151

Aigner T, Gresk-otter KR, Fairbank JC, von der Mark K, Urban JP

Variation with age in the pattern of type X collagen expression in normal and scoliotic human intervertebral discs

Calcif Tissue, 1998, 63:263

Alexander RM

Elasticity in human and animal backs

In: Movement, Stability and Low Back Pain. The Essential Role of the Pelvis

Vleeming A, Mooney V, Snijders CJ, Doramn TA, Stoeckart R (eds)

Churchill Livingstone, New York, 1997

Antoniou J, Goudsouzian NM, Heathfield TF, Winterbottom N, Steffen T, Poole AR, Aebi M, Alini M

The human lumbar endplate. Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration

Spine, 1996, 21:1153

Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M

The human lumbar intervertebral disc. Evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration

J Clin Invest, 1966, 98:996

Aprill C, Bogduk N

High-intensity zone. A diagnostic sign of painful lumbar disc on magnetic resonance imaging

Brit J Radiol, 1992, 65:361

Ayotte DC, Ito K, Tepic S

Direction-dependent resistance to flow in the endplate of the intervertebral disc. An ex vivo study

J Orthop Res, 2001, 19:1073

B

Beggs I, Addison J

Posterior vertebral rim fractures

Brit J Radiol, 1998, 71:567

Benneker LM, Heini PF, Alini M, Anderson SE, Ito K

2004 Young Investigator Award Winner. Vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration

Spine, 2005, 30:167

Bernick S, Cailliet R

Vertebral end-plate changes with aging of human vertebrae

Spine, 1982, 7:97

Bibby SR, Jones DA, Ripley RM, Urban JP

Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells

Spine, 2005, 30:487

Bogduk N, Twomey LT

The inter-body joints and the intervertebral discs

In: Clinical anatomy of the lumbar spine, 2nd ed

Bogduk N, Twomey LT (eds)

Churchill Livingstone, Melbourne, 1991:11

Bogduk N, Tynan W, Wilson AS

The nerve supply to the human lumbar intervertebral discs

J Anat, 1981, 132:39

Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG

Classification of age-related changes in lumbar intervertebral discs. 2002 Volvo Award in basic science

Spine, 2002, 27:2631

Bowden REM

Anatomy of the Human Spine

In: Surgery of the spine. A combined orthopaedic and neurosurgical approach

Findlay G, Owen R (eds)

Blackwell Scientific Publications, Oxford, 1992:45

Brinckmann P, Frobin W, Hierholzer E, Horst M

Deformation of the vertebral end-plate under axial loading of the spine

Spine, 1983, 8:851

Brinckmann P, Grootenboer H

Change of disc height, radial disc bulge, and intradiscal pressure from discectomy. An in vitro investigation on human lumbar discs

Spine, 1991, 16:641

Broberg KB

On the mechanical behaviour of intervertebral discs

Spine, 1983, 8:151

Brown MF, Hukkanen MV, McCarthy ID, Redfern DR, Batten JJ, Crock HV, Hughes SP, Polak JM

Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease

J Bone Joint Surg, 1997, 79B:147

Buckwalter JA

Aging and degeneration of the human intervertebral disc

Spine, 1995, 20:1307

Buckwalter JA, Mow VC, Boden SD, Eyre DR, Weidenbaum M

Intervertebral disk structure, composition, and mechanical function

In: Orthopaedic basic sciences. Biology and biomechanics of the musculoskeletal system (2nd ed)

Buckwalter JA, Einhorn TA, Simon SR (eds)

Chicago, American Academy of Orthopaedic Surgeons, 2000:547

Buckwalter JA, Pedrini-Mille A, Pedrini V, Tudisco C

Proteoglycans of human infant intervertebral disc. Electron microscopic and biochemical studies

J Bone Joint Surg, 1985, 67A:284

Butler D, Trafimow JH, Andersson GB, McNeill TW, Huckman MS

Discs degenerate before facets

Spine, 1990, 15:111

C

Cassidy JJ, Hiltner A, Baer E

Hierarchical structure of the intervertebral disc

Connect Tissue Res, 1989, 23:75

Cheung KM, Karppinen J, Chan D, Ho DW, Song YQ, Sham P, Cheah KS, Leong JC, Luk KD

Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals

Spine, 2009, 34:934

Choi KS, Cohn MJ, Harfe BD

Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse. Implications for disk degeneration and chordoma formation

Dev Dyn, 2008, 237:3953

Coppes MH, Marani E, Thomeer RT, Groen GJ

Innervation of "painful" lumbar discs

Spine, 1997, 22:2342

Coventry MB, Ghormley RK, Kernohan JW

The intervertebral disc. Its microscopic anatomy and pathology. Part I. Anatomy, development, and physiology

J Bone Joint Surg, 1945, 27A:105

Crock HV Internal disc disruption. A challenge to disc prolapse fifty years on

Spine, 1986, 11:650

Crock HVTraumatic disc injury

In: Handbook of clinical neurology. Vinken PJ en Bruyn GW (eds)

Volume 25: Injuries of the spine and spinal cord. Part I (edited in collaboration of Braakman R)

North-Holland Publishing Company, Amsterdam, 1976, Chapter 19:481

Crock HV, Goldwasser M

Anatomic studies of the circulation in the region of the vertebral end-plate in adult Greyhound dogs

Spine, 1984, 9:702

Crock HV, Yoshizawa H

The blood supply of the vertebral column and spinal cord in man

1977, New York, Vienna Springer Verlag , New York, 1977

D

De Palma AF, Rothman RH

The intervertebral disc (1st ed)

De Palma AF, Rothman RH (eds)

Philadelphia, Saunders, 1970

Donisch EW, Trapp W

The cartilage endplates of the human vertebral column (some considerations of postnatal development)

Anat Rec, 1971, 169:705

Duncan NA

Cell deformation and micromechanical environment in the intervertebral disc

J Bone Joint Surg, 2006, 88A(Suppl 2):47

E

Ebara S, Iatridis JC, Setton LA, Foster RJ, Mow VC, Weidenbaum M

Tensile properties of nondegenerate human lumbar anulus fibrosus

Spine, 1996, 21:452

Edelson JG, Nathan H

Stages in the natural history of the vertebral end-plates

Spine, 1988, 13:21

Edwards WT, Zheng Y, Ferrara LA, Yuan HA

Structural features and thickness of the vertebral cortex in the thoracolumbar spine

Spine, 2001, 26:218

F

Fagan A, Moore R, Vernon Roberts B, Blumbergs P, Fraser R

ISSLS prize winner. The innervation of the intervertebral disc. A quantitative analysis

Spine, 2003, 28:2570

Farfan HF Mechanical disorders of the low back

Lea & Febiger, Philadelphia, 1973

Farfan HF, Cossette JW, Robertson GH, Wells RV, Kraus H

The effects of torsion on the lumbar intervertebral joints. The role of torsion in the production of disc degeneration

J Bone Joint Surg, 1970, 52A:468

Finch P        Technology Insight. Imaging of low back pain

Nat Clin Pract Rheumatol, 2006, 2:554

François RJ, Dhem A

Microradiographic study of the normal human vertebral body

Acta Anat, 1974, 89:251

Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O'Brien J, Jayson MI

Nerve ingrowth into diseased intervertebral disc in chronic back pain

The Lancet, 1997, 350:178

Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, Ross ER, O'Brien JP, Hoyland JA

Nerve growth factor expression and innervation of the painful intervertebral disc

J Pathol, 2002, 197:286

Frobin W , Brinckmann P, Biggemann M, Tillotson M, Burton K

Precision measurement of disc height, vertebral height and sagittal plane displacement from lateral radiographic views of the lumbar spine

Clin Biomech, 1997, 12(Suppl 1):S1

Fujita Y, Duncan NA, Lotz JC

Radial tensile properties of the lumbar annulus fibrosus are site and degeneration dependent

J Orthop Res, 1997, 15:814

G

Galante JO

Tensile properties of the human lumbar annulus fibrosus

Acta Orthop Scand, 1967, Suppl 100:1

Goel VK, Monroe BT, Gilbertson LG, Brinckmann P

Interlaminar shear stresses and laminae separation in a disc. Finite element analysis of the L3-L4 motion segment subjected to axial compressive loads

Spine, 1995, 20:689

Gordon SJ, Yang KH, Mayer PJ, Mace AH Jr, Kish VL, Radin EL

Mechanism of disc rupture. A preliminary report

Spine, 1991, 16:450

Grant JP, Oxland TR, Dvorak MF

Mapping the structural properties of the lumbosacral vertebral endplates

Spine, 2001, 26:889

Green TP, Adams MA, Dolan P

Tensile properties of the annulus fibrosus II. Ultimate tensile strength and fatigue life

Eur Spine J, 1993, 2:209

H

Hampton D, Laros G, McCarron R, Franks D

Healing potential of the anulus fibrosus

Spine, 1989, 14:398

Handa T, Ishihara H, Ohshima H, Osada R, Tsuji H, Obata K

Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar

intervertebral disc

Spine, 1997, 22:1085

Happey F, Johnson AG, Naylor A, Turner RL

Preliminary observations concerning the fine structures of the intervertebral disc

J Bone Joint Surg, 1964, 46B:563

Harris RI, MacNab

Structural changes in the lumbar intervertebral disc. Their relationship to low back pain and sciatica

J Bone Joint Surg, 1954, 36B:304

Hassler O The human intervertebral disc. A micro-angiographical study on its vascular supply at various ages

Acta Orthop Scand, 1969, 40:765

Hickey DS, Hukins DW

Relation between the structure of the annulus fibrosus and the function and failure of the intervertebral disc

Spine, 1980, 5:106

Hickey DS, Hukins DW

Collagen fibril diameters and elastic fibres in the annulus fibrosus of human fetal intervertebral disc

J Anat, 1981, 133:351

Hilton RC, Ball J

Vertebral rim lesions in the dorsolumbar spine

Ann Rheum Dis, 1984, 43:302

Hirsch C, Schajowicz F

Studies on structural changes in the lumbar annulus fibrosus

Acta Orthop Scand, 1953, 22:184

Holm S, Holm AK, Ekström L, Karladani A, Hansson T

Experimental disc degeneration due to endplate injury

J Spinal Disord Tech, 2004, 17:64

Horton WG

Further observations on the elastic mechanism of the intervertebral disc

J Bone Joint Surg, 1958, 40B:552

Hsu KY, Zucherman JF, Derby R, White AH, Goldthwaite N, Wynne G

Painful lumbar end-plate disruptions. A significant discographic finding

Spine, 1988, 13:76

Hukins DWL

Disc structure and function

In: The biology of the intervertebral disc

Ghosh P (ed)

Florida, Boca Raton, CRC Press, 1988:1

Humzah MD, Soames RW

Human intervertebral disc. Structure and function

Anat Rec, 1988, 220:337

I

Inoue H        Three-dimensional architecture of lumbar intervertebral discs

Spine, 1981, 6:139

Ishihara H, McNally DS, Urban JP, Hall AC

Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk

J Appl Physiol, 1996, 80:839

J

Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D, Ross JS

Magnetic resonance imaging of the lumbar spine in people without back pain

N Engl J Med, 1994, 331:69

Johnson EF, Berryman H, Mitchell R, Wood WB

Elastic fibres in the anulus fibrosus of the adult human lumbar intervertebral disc. A preliminary report

J Anat, 1985, 143:57

Johnson EF, Chetty K, Moore IM, Stewart A, Jones W

The distribution and arrangement of elastic fibres in the intervertebral disc of the adult human

J Anat, 1982, 135:301

K

Kääpä E, Han X, Holm S, Peltonen J, Takala T, Vanharanta H

Collagen synthesis and types I, III, IV, and VI collagens in an animal model of disc degeneration

Spine, 1995, 20:59

Kasra M, Goel V, Martin J, Wang ST, Choi W, Buckwalter J

Effect of dynamic hydrostatic pressure on rabbit intervertebral disc cells

J Orthop Res, 2003, 21:597

Keith A        Human embryology and morphology (6th ed)

Edward Arnold Co, London, 1948

Kerttula LI, Serlo WS, Tervonen OA, Pääkkö EL, Vanharanta HV

Post-traumatic findings of the spine after earlier vertebral fracture in young patients: clinical and MRI study

Spine, 2000, 25:1104

Kim Y        Prediction of peripheral tears in the anulus of the intervertebral disc

Spine, 2000, 25:1771

Kokkonen SM, Kurunlahti M, Tervonen O, Ilkko E, Vanharanta H

Endplate degeneration observed on magnetic resonance imaging of the lumbar spine. Correlation with pain provocation and disc changes observed on computed tomography diskography

Spine, 2002, 27:2274

Konttinen YT, Grönblad M, Antti-Poika I, Seitsalo S, Santavirta S, Hukkanen M, Polak JM

Neuroimmunohistochemical analysis of peridiscal nociceptive neural elements

Spine, 1990, 15:383

Krismer M, Haid C, Rabl W

The contribution of annulus fibers to torque resistance

Spine, 1996, 21:2551

L

Liu GZ, Ishihara H, Osada R, Kimura T, Tsuji H

Nitric oxide mediates the change of proteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure

Spine, 2001, 26:134

Lundin O, Ekström L, Hellström M, Holm S, Swärd L

Exposure of the porcine spine to mechanical compression. Differences in injury pattern between adolescents and adults

Eur Spine J, 2000, 9:466

Lundin O, Ekström L, Hellström M, Holm S, Swärd L

Injuries in the adolescent porcine spine exposed to mechanical compression

Spine, 1998, 23:2574

Lyons G, Eisenstein SM, Sweet MB

Biochemical changes in intervertebral disc degeneration

Biochim Biophys Acta, 1981, 673:443

M

Marchand F, Ahmed AM

Investigation of the laminate structure of lumbar disc annulus fibrosus

Spine, 1990, 15:402

Marketos SG, Skiadas P

Hippocrates. The father of spine surgery

Spine, 1999, 24:1381

Maroudas A, Stockwell RA, Nachemson A, Urban J

Factors involved in the nutrition of the human lumbar intervertebral disc. Cellularity and diffusion of glucose in vitro

J Anat, 1975, 120:113

McCann MR, Tamplin OJ, Rossant J, Séguin CA

Tracing notochord-derived cells using a Noto-cre mouse. Implications for intervertebral disc development

Dis Model Mech, 2012, 5:73

McDevitt CA

Proteoglycans of the intervertebral disc

In: Biology of the intervertebral disc

Ghosh P (ed)

CRC Press, Boca Raton, 1988:151

McFadden KD, Taylor JR

End-plate lesions of the lumbar spine

Spine, 1989, 14:867

McNally DS, Adams MA, Goodship AE

Development and validation of a new transducer for intradiscal pressure measurement

J Biomed Eng, 1992, 14:495

McNally DS, Adams MA

Internal intervertebral disc mechanics as revealed by stress profilometry

Spine, 1992, 17:66

Melrose J, Ghosh P, Taylor TK, Hall A, Osti OL, Vernon-Roberts B, Fraser RD

A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus

J Orthop Res, 1992, 10:665

Miller JA, Schmatz C, Schultz AB

Lumbar disc degeneration. Correlation with age, sex, and spine level in 600 autopsy specimens

Spine, 1988, 13:173

Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR

Degenerative disk disease. Assessment of changes in vertebral body marrow with MR imaging

Radiology, 1988, 166:193

Moore RJ The vertebral endplate. Disc degeneration, disc regeneration

Eur Spine J, 2006, 15(Suppl 3):333

Moore RJ, Osti OL, Vernon-Roberts B, Fraser RD 

Changes in endplate vascularity after an outer anulus tear in the sheep

Spine, 1992, 17:874

Moore RJ, Vernon-Roberts B, Fraser RD, Osti OL, Schembri M

The origin and fate of herniated lumbar intervertebral disc tissue

Spine, 1996, 21:2149

Mulholland RC

The myth of lumbar instability. The importance of abnormal loading as a cause of low back pain

Eur Spine J 2008, 17:619-625

Mwale F, Roughley P, Antoniou J

Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage. A requisite for tissue engineering of intervertebral disc

Eur Cell Mater, 2004, 8:58

N

Nachemson A, Lewin T, Maroudas A, Freeman MA

In vitro diffusion of dye through the end-plates and the annulus fibrosus of human lumbar inter-vertebral discs

Acta Orthop Scand, 1970, 41:589

Natarajan RN, Ke JH, Andersson GB

A model to study the disc degeneration process

Spine, 1994, 19:259

Neidlinger-Wilke C, Würtz K, Urban JP, Börm W, Arand M, Ignatius A, Wilke HJ, Claes LE

Regulation of gene expression in intervertebral disc cells by low and high hydrostatic pressure

Eur Spine J, 2006, 15(Suppl 3):S372

Nerlich AG, Schleicher ED, Boos N

Immunohistologic markers for age-related changes of human lumbar intervertebral discs. 1997 Volvo Award winner in basic science studies.

Spine, 1997, 22:2781

O

Oda J, Tanaka H, Tsuzuki N

Intervertebral disc changes with aging of human cervical vertebra. From the neonate to the eighties

Spine, 1988, 13:1205

Oegema TR Jr

Biochemistry of the intervertebral disc

Clin Sports Med, 1993, 12:419

Oki S, Matsuda Y, Shibata T, Okumura H, Desaki J

Morphologic differences of the vascular buds in the vertebral endplate. Scanning electron microscopic study

Spine, 1996, 21:174

Osti OL, Vernon-Roberts B, Fraser RD

1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model

Spine, 1990, 15:762

Osti OL, Vernon-Roberts B, Moore R, Fraser RD

Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs

J Bone Joint Surg, 1992, 74B:678

P

Paajanen H, Lehto I, Alanen A, Erkintalo M, Komu M

Diurnal fluid changes of lumbar discs measured indirectly by magnetic resonance imaging

J Orthop Res, 1994, 12:509

Palmgren T, Grönblad M, Virri J, Kääpä E, Karaharju E

An immunohistochemical study of nerve structures in the anulus fibrosus of human normal lumbar intervertebral discs

Spine, 1999, 24:2075

Panjabi MM, White AA III

Intervertebral disc

In: Clinical biomechanics of the spine (2nd ed)

White AA III, Panjabi MM (eds)

JB Lippincott, Philadelphia, 1990:3

Park WM, McCall IW, O'Brien JP, Webb JK

Fissuring of the posterior annulus fibrosus in the lumbar spine

Brit J Radiol, 1979, 52:382

Peacock A Observations on the postnatal structure of the intervertebral disc in man

J Anat, 1952, 86:162

Pearce RH, Grimmer BJ, Adams ME

Degeneration and the chemical composition of the human lumbar intervertebral disc

J Orthop Res, 1987, 5:198

Peng B, Hao J, Hou S, Wu W, Jiang D, Fu X, Yang Y

Possible pathogenesis of painful intervertebral disc degeneration

Spine, 2006, 31:560

Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y

The pathogenesis of discogenic low back pain

J Bone Joint Surg, 2005, 87B:62

Pezowicz CA, Robertson PA, Broom ND

Intralamellar relationships within the collagenous architecture of the annulus fibrosus imaged in its fully hydrated state

J Anat, 2005, 207:299

Pfirrmann CW, Metzdorf A, Elfering A, Hodler J, Boos N

Effect of aging and degeneration on disc volume and shape. A quantitative study in asymptomatic volunteers

J Orthop Res, 2006, 24:1086

Piccolo S        Mechanics in the embryo

Nature, 2013, 504:223

Pollintine P, Przybyla AS, Dolan P, Adams MA

Neural arch load-bearing in old and degenerated spines

J Biomech, 2004, 37:197

Pooni JS, Hukins DW, Harris PF, Hilton RC, Davies KE

Comparison of the structure of human intervertebral discs in the cervical, thoracic and lumbar regions of the spine

Surg Radiol Anat, 1986, 8:175

Pritzker KP

Aging and degeneration in the lumbar intervertebral disc

Orthop Clin North Am, 1977, 8:66

Przybyla A, Pollintine P, Bedzinski R, Adams MA

Outer annulus tears have less effect than endplate fracture on stress distributions inside intervertebral discs: relevance to disc degeneration

Clin Biomech, 2006, 21:1013

R

Ratcliffe JF

The arterial anatomy of the developing human dorsal and lumbar vertebral body. A microarteriographic study

J Anat, 1981, 133:625

Rauschning W

Anatomy and pathology of the lumbar spine

In: The adult spine. Principles and practice

Frymoyer JW (ed-in-chief)

Raven Press, New York, 1991, Chapter 67:1465

Roberts S, Caterson B, Menage J, Evans EH, Jaffray DC, Eisenstein SM

Matrix metalloproteinases and aggrecanase. Their role in disorders of the human intervertebral disc

Spine, 2000, 25:3005

Roberts S, McCall IW, Menage J, Haddaway MJ, Eisenstein SM

Does the thickness of the vertebral subchondral bone reflect the composition of the intervertebral disc?

Eur Spine J, 1997, 6:385

Roberts S, Menage J, Urban JP

Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc

Spine, 1989, 14:166

Rolander SD, Blair WE

Deformation and fracture of the lumbar vertebral end plate

Orthop Clin North Am, 1975, 6:75

Roughley PJ

Biology of intervertebral disc aging and degeneration. Involvement of the extracellular matrix

Spine, 2004, 29:2691

S

Sato K, Kikuchi S, Yonezawa T

In vivo intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems

Spine, 1999, 24:2468

Setton LA, Zhu W, Weidenbaum M, Ratcliffe A, Mow VC

Compressive properties of the cartilaginous end-plate of the baboon lumbar spine

J Orthop Res, 1993, 11:228

Shao Z, Rompe G, Schiltenwolf M

Radiographic changes in the lumbar intervertebral discs and lumbar vertebrae with age

Spine, 2002, 27:263

Sivakamasundari V, Lufkin T

Bridging the gap. Understanding embryonic intervertebral disc development

Cell Dev Biol, 2012, 1:103

Skrzypiec D, Tarala M, Pollintine P, Dolan P, Adams MA

When are intervertebral discs stronger than their adjacent vertebrae?

Spine, 2007, 32:2455

Slipman CW, Patel RK, Zhang L, Vresilovic E, Lenrow D, Shin C, Herzog R

Side of symptomatic annular tear and site of low back pain. Is there a correlation?

Spine, 2001, 26:E165

Stern CD Gastrulation. From Cells to Embryo

Laboratory Press, Cold Spring Harbor, New York, 2004

T

Tanaka M, Nakahara S, Inoue H

A pathologic study of discs in the elderly. Separation between the cartilaginous endplate and the vertebral body

Spine, 1993, 18:1456

Taylor JR Growth of human intervertebral discs and vertebral bodies

J Anat, 1975, 120:49

Taylor JR Persistence of the notochordal canal in vertebrae

J Anat, 1972, 111:211

Tsuji H, Hirano N, Ohshima H, Ishihara H, Terahata N, Motoe T

Structural variation of the anterior and posterior anulus fibrosus in the development of human lumbar intervertebral disc. A risk factor for intervertebral disc rupture

Spine, 1993, 18:204

Twomey L, Taylor J

Age changes in lumbar intervertebral discs

Acta Orthop Scand, 1985, 56:496

Twomey LT, Taylor JR

Age changes in lumbar vertebrae and intervertebral discs

Clin Orthop Relat Res, 1987, 224:97

U

Urban JP, Holm S, Maroudas A

Diffusion of small solutes into the intervertebral disc. As in vivo study

Biorheology, 1978, 15:203

Urban J, Maroudas A

The chemistry of the intervertebral disc in relation to its physiological function

Clin Rheum Dis 1980; 6:51

Urban JP, Maroudas A

Swelling of the intervertebral disc in vitro

Connect Tissue Res, 1981, 9:1

Urban JP, Roberts S

Degeneration of the intervertebral disc

Arthritis Res Ther, 2003, 5:120

Urban JPG, Maroudas A

The measurement of fixed charged density in the intervertebral disc

Biochim Biophys Acta, 1979, 586:166

Urban JPG, Roberts S

Development and degeneration of the intervertebral discs

Mol Med Today, 1995, 1:329

Urban JPG, Roberts S, Ralphs JR

The nucleus of the intervertebral disc from development to degeneration

Am Zool, 2000, 40:53

V

Veres SP, Robertson PA, Broom ND

ISSLS prize winner. Microstructure and mechanical disruption of the lumbar disc annulus. Part II. How the annulus fails under hydrostatic pressure

Spine, 2008, 33:2711

Vernon-Roberts B, Fazzalari NL, Manthey BA

Pathogenesis of tears of the anulus investigated by multiple-level transaxial analysis of the T12-L1 disc

Spine, 1997, 22:2641

Vernon-Roberts B, Pirie CJ

Degenerative changes in the intervertebral discs of the lumbar spine and their sequelae

Rheumatol Rehabil, 1977, 16:13

Vernon-Roberts B, Pirie CJ

Healing trabecular microfractures in the bodies of lumbar vertebrae

Ann Rheum dis, 1973, 32:406

Videman T, Battié MC, Gibbons LE, Maravilla K, Manninen H, Kaprio J

Associations between back pain history and lumbar MRI findings

Spine, 2003, 28:582

Videman T, Nurminen M

The occurrence of anular tears and their relation to lifetime back pain history. A cadaveric study using barium sulfate discography

Spine, 2004, 29:2668

W

Wallace AL, Wyatt BC, McCarthy ID, Hughes SP

Humoral regulation of blood flow in the vertebral endplate

Spine, 1994, 19:1324

Watanabe H, Yamada Y, Kimata K

Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function

J Biochem, 1998, 124:687

Weiler C, Nerlich AG, Zipperer J, Bachmeier BE, Boos N

2002 SSE Award Competition in Basic Science. Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption

Eur Spine J, 2002, 11:308

Weinstein JN, Gordon SL (eds)

Low back pain. A scientific and clinical overview (1st ed)

American Academy Orthopaedic Surgeons, North River Road 6300, Rosemont, IL, 1996

Weishaupt D, Zanetti M, Hodler J, Min K, Fuchs B, Pfirrmann CW, Boos N

Painful Lumbar Disk Derangement. Relevance of Endplate Abnormalities at MR Imaging

Radiology, 2001, 218:420

Whalen JL, Parke WW, Mazur JM, Stauffer ES

The intrinsic vasculature of developing vertebral end plates and its nutritive significance to the intervertebral discs

J Pediatr Orthop, 1985, 5:403

White AA III, Panjabi MM (eds)

Clinical biomechanics of the spine (2nd ed)

JB Lippincott, Philadelphia, 1990

Wilke HJ, Krischak ST, Wenger KH, Claes LE

Load-displacement properties of the thoracolumbar calf spine: experimental results and comparison to known human data

Eur Spine J, 1997, 6:129

Y

Yasuma T, Koh S, Okamura T, Yamauchi Y

Histological changes in aging lumbar intervertebral discs. Their role in protrusions and prolapses

J Bone Joint Surg, 1990, 72A:220

Yoshizawa H, O'Brien JP, Smith WT, Trumper M

The neuropathology of intervertebral discs removed for low-back pain

J Pathol, 1980, 132:95

Yu J, Fairbank JC, Roberts S, Urban JP

The elastic fiber network of the anulus fibrosus of the normal and scoliotic human intervertebral disc

Spine, 2005, 30:1815

Yu J, Winlove PC, Roberts S, Urban JP

Elastic fibre organization in the intervertebral discs of the bovine tail

J Anat, 2002, 201:465

Yu SW, Haughton VM, Ho PS, Sether LA, Wagner M, Ho KC

Progressive and regressive changes in the nucleus pulposus. Part II. The adult

Radiology, 1988, 169:93

Z

Zhao F, Pollintine P, Hole BD, Dolan P, Adams MA

Discogenic origins of spinal instability

Spine, 2005, 30:2621

Zhao FD, Pollintine P, Hole BD, Adams MA, Dolan P

Vertebral fractures usually affect the cranial endplate because it is thinner and supported by less-dense trabecular bone

Bone, 2009, 44:372