LUMBAR INTERVERTEBRAL DISC (IVD).

BIOMECHANICAL FUNCTION

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, Flanders, Belgium

Artistic excellence: 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 Tine. June 2015.

That particular day began with a rather unconventional handshake: the jarring compressions of the heels of her hands against my sternum and gazing into each other’s eyes. It was real enough, just … limited. Inside, I could be anywhere or everywhere, do anything, be anything. She asked about my world. Past events were common. She knew me since 2,000 years. In our lives, we made so many wrong choices, dialed with so many deceptions, wasted so many opportunities, exhausted our resources, lost so much. She just was like me and my life. I saw my reflection in her and was transfixed.

Strangely enough, she understood that by saying to-morrow she would run out of time. Sometimes the human animal needs to become an amnesiac creature. Enjoying the enchantment of her personality, she could dissolve some of the frost from my previous lives. Ha ha, I must have looked strange to her. To me, everything looked ok. Arms, legs, torso … yes, human! No longer artificial presence to hide mysteries, secrets, frustrations and deceptions! No! A phenomenal person whose eyes sparkle with animation.

www.guy-declerck.com

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 23,539 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

Contents

Note: initially reading the chapter ‘extracellular matrix’ will make it easier to understand this chapter

1. In vivo mechanical analysis of lumbar intervertebral disc is barely possible

2. Functional spinal unit (FSU)

3. Morphological development of lumbar IVD. Influence of genetics and loading

4. Quantitative range of motion (ROM) of the lumbar IVD

5. Qualitative ROM of the lumbar IVD

6. Stabilizing spinal muscular activity

7. Musculoskeletal system continuously responds to its loading environment

8. Disc loading influences disc cell metabolism

9. Purpose of understanding impact of disc loading on disc cell metabolism

10. Study models need to elucidate relationships between biology and mechanics

11. Loading of aging spine

12. Search for etiological factors in degenerative processes in IVD

13. Hypermobility of degenerative spinal segment

14. ‘Clinical’ spinal instability does not exist

15. Animal models are extremely important

16. Humans and animals have some IVD similarities

17. Experimental models indicate existence of mechanical damage to IVDs

18. Primary role of lumbar IVD

19. IVD biomechanics and (discogenic) low back pain

20. Alterations in mechanical behavior affect all spinal structures

21. Functional behavior of lumbar IVD requires mechanical interplay between EPS, NP, and AF

22. Functional behavior of NP. Incompressibility of water & viscoelastic dissipation

23. Osmotic pressures in NP

24. Biomechanical viscoelastic behavior of AF

25. IVD continuously responds to spinal compressive forces

26. Hydrostatic pressure in IVD

27. Compressive stiffness provided by IVD

28. IVDs have difficulties resisting loads in shear

29. Deprivation of mechanical stimuli impairs IVDs. Unloading IVD

30. IVD impairment by non-physiological motion and deprivation of motion

31. Compressive vs distractive effects on degenerating IVD

32. Effect of normal loading patterns on IVD

33. ‘Excessive’ IVD loading patterns

34. Different positional loading patterns. Standing, sitting, bending, hyperflexion

35. Vibration as loading mechanism

36. Loading scoliotic IVDs

37. Altered IVD loading in fused and adjacent fused spinal segments

38. Complex but precarious balance and interplay between biologic and biomechanical influences

39. Cells recognise different daily mechanical patterns

40. Mechanical loads influence anabolic and catabolic functions of IVD cells

41. Mechanism of cellular mechanical signal transduction (mechanotransduction)

42. Possible existence of a ‘mechanostat’

43. Mechanotransduction significantly varies with genotype

44. Biomechanics and degeneration of lumbar IVD

45. Biomechanics and degeneration of nucleus pulposus

46. Biomechanics and degeneration of endplates and annulus fibrosus

47. Biomechanics and potential pain production

48. Conclusion by the author

49. Literature Encyclopaedia

1. In vivo mechanical analysis of lumbar intervertebral disc (IVD) is barely possible

In vivo mechanical analysis of the human spine in the living person by whatever means is barely possible. Animal, biomechanical and mathematical modelling and simulation of this most complex biological spinal structural system remains essential in order to understand the mechanical behaviour of the lumbar intervertebral discs and the lumbar spine as a whole under different mechanical loading conditions which the lumbar spine undergoes on daily basis (Gracovetsky).

2. Functional Spinal Unit (FSU)

To analyse and to study the biomechanical characteristics of the lumbar spine the term ‘functional spinal motion unit (FSU)’ has been introduced. A motion segment consists of two vertebral bodies, the intervening IVD, the paired posterior zygapophyseal facetal joints, the ligaments, muscles and tendons. Simply expressed, a functional spinal motion segment is an IVD sandwiched in between two vertebrae.

The combination of the cartilaginous endplates (EPs), the nucleus pulposus (NP) and the annulus fibrosus (AF) makes the FSU an efficient coupling unit provided all the structures remain intact.

3. Morphological development of lumbar IVD. Influence of genetics and loading

The development of the lumbar IVD, consisting of the NP and the AF, is influenced both by intrinsic genetic factors and by the mechanical loading environment. The morphological composition of the lumbar IVD changes significantly during its development and growth, aging and degenerative processes. This evolution in turn alters the way the IVD responds to changes in mechanical stress (stress = F/m² = N/m² = Pa).

The daily different mechanical loading stimuli (compression, tension, stretch, strains, fluid shear stress, etc …) induce differential gene expressions so that the cells in the IVD are able or remain unable to regulate the morphological appearance and properties of the complete IVD throughout full development.

Inappropriate mechanical loading will develop degenerative processes in the IVD more easily in some individuals than in others. This cannot solely be explained by differences in neuromuscular spinal control. In most circumstances it is due as well to the presence of unfavourable genetic inheritance (in 70 % of all individuals).

4. Quantitative range of motion (ROM) of lumbar IVD

The range of motion at the IVD level is described quantitatively and qualitatively. Quantitative spinal ROM is easily measured in vivo. A healthy young lumbar IVD allows ~ 14° flexion-extension at all levels, ~ 4° lateral bending, and 1,5° axial rotation. However, the amount of motion at L5-S1 is considerably less. Consequently, an IVD allows mobility, flexibility and stability but resists translational and angular ROM (Pearcy).

The lumbar IVD has 6 degrees of freedom, allowing independent translation and independent angular motion around each of the three anatomic axes (Panjabi; Sears). The ligaments and joint capsules contribute very little, if anything, toward maintaining spinal stability. The trunk musculature is the major force-generating structure (see below).

5. Qualitative range of motion (ROM) of lumbar IVD

Qualitative spinal ROM only can be measured in vitro during experimental laboratory evaluations. This pattern of motion at IVD level is expressed by a characteristic sigmoidal load-displacement-curve when subjected to flexion-extension moments (nicely presented in White’s book). Some well-known mathematically measured parameters of the qualitative spinal ROM are the neutral zone, centrode, floating instantaneous axis of rotation (IAR), and the dynamic centre of rotation (COR) (Gertzbein; Sears; Schmidt; White).

Then, it’s evident that the normal spinal motion segment is more than a simple hinge joint around a single axis of rotation. The CORs change constantly during movements, but each IAR remains within an elliptical locus called the centrode of motion. In a normal spine, the centrodes of motion are narrow, located in the posterior one-third of the disc, and have a length on average of 21 mm.

Scientifically oriented researchers use the mathematical variables of qualitative spinal ROM for research and development of more appropriate and innovative spinal treatment possibilities because the qualitative parameters are highly affected by the intradiscal degenerative processes. Indeed, a simple plate-and-screw system or prosthesis is not able to ‘restore’ qualitative ROM.

6. Stabilizing spinal muscular activity

Because of its inherent instability, the spine must be stabilized by a combination of muscular and spinal stiffness* (Stokes). But under nearly all circumstances of sitting, standing, walking, bending and hyperflexion, muscular forces form the largest contribution to spinal loading.

In the active person, trunk muscles are continuously activated to secure spine stability. Consequently, those who exercise and are physically fit people are reported to have a decreased incidence of acute low back pain episodes.

In contrast, a sedentary life is rather associated with the potential of developing chronic low back pain (CLBP). Once low back pain has developed, LBP sufferers unconsciously hyperactivate their stabilizing muscles to stiffen their trunk against painful motion. No doubt this situation further enhances the stability of the spine but, unfortunately, occurs at the expense of more spinal loading.

* Stiffness is a measure of resistance offered to external loads by a structure when it undergoes  

   deformation.

7. Musculoskeletal system continuously responds to its loading environment

The musculoskeletal system responds continuously - both positively and negatively - to its loading environment. As such, the influences of mechanical loading on biological tissues (cells, tissues, organs) have been studied since long time. Remember Wolff’s law.

The IVD joint is continuously subjected to the daily imposed loads, reacts with deformations related to stresses, forces and moments during motion of the spine, and gradually but finally sustains fatigue damage and injuries.

8. Disc loading influences disc cell metabolism

Lumbar IVDs in humans are continuously subjected to varying mechanical forces at all times. Under normal conditions the IVD is subjected to Wolff's law. Applied stresses and forces affect cellular activity allowing the IVD to (temporarily) remodel its extracellular matrix (ECM) and to reduce the impact of stress. Indeed, the production of both proteoglycans and of degrading matrix metalloproteinases (MMPs) by IVD cells is influenced by a variety of mechanical signals (see below).

9. Purpose of understanding impact of disc loading on disc cell metabolism

It is important to understand the complex behavioral responses of the cells and the ECMs because exposure to prolonged and repetitive normal but changing stresses and high levels of static compressive forces (F = 1m/s² = Newton) are important factors leading to IVD degeneration. It remains essential to understand how IV disc tissue damage accumulates under various static and dynamic mechanical loading patterns and how disc degeneration may cause painful signs and symptoms.

All outcome studies of the extensive variety of actual existing non-operative and surgical approaches treating painful degenerative discogenic conditions indicate their limited efficacy in the long term. This conclusion urges for innovative biologic therapeutic strategies toward repair and/or stabilization of the ECM tissue of the IVD during a specific stage of degeneration.

10. Study models need to elucidate relationships between biology and mechanics

Different study models are used to elucidate the interrelationship between loading of the IVD cell and its metabolism. The three main questions remain:

(1) how do daily mechanical loads and strains change the physical signals between the ECM and the IV disc cells?

(2) how do the degradative and structural changes in the EC matrices interact with the biosynthetic mechanisms of the IV disc cells? and

(3) how do these interactions initiate the degenerative processes in the ECM of the normal aging intervertebral disc?

11. Loading of aging IVD

Once the aging processes have started in the NP, further internal disc disruption and continuous normal and abnormal loading patterns may lead to degenerative tears in the AF and degenerative fissures or ruptures in the cartilaginous EPs which result in abnormalities in the adjacent vertebral bodies (Fig. 11).

Fig. 11. Normal aging process in the L3-L4 intervertebral disc. The central nucleus shows the typical aging brown colour. The endplates and surrounding annulus remain intact. At the L4-L5 disc level the degenerative lesions are visualised. The brown nucleus is disrupted internally and cannot longer be distinguished from the annulus. The annulus is ruptured through which nuclear material could have herniated. In the upper endplate, microfractures, fissures and ruptures are clearly seen. Degenerative endproducts from the nucleus have migrated through these fissures into the L4 vertebral body. Hence, the discoloration in part of these osseous structures which is compatible with the Modic-sign on MRI. The lower L4 endplate evidences ruptures as well. The annulus at the level of the L5-S1 disc is ruptured and part of the nucleus migrated into the spinal canal.The endplates are fissured. At these levels vertebra bone is discoloured. The laminar structure of the annulus is nicely documented.

 (A90-139, male, 50 yrs / Declerck / Kakulas, Neuropathology, Perth, Western Australia).

12. Search for etiological factors in degenerative processes in IVD

Direct evaluation of how different biomechanical loading patterns influence the degradative processes in the human IVD is not possible. Although the impact of muscular forces on the spine can be evaluated, the pressures in the IVD can be measured, the motion in the different lumbar segments can be analyzed, and diffusion into the IVDs can be assessed by MRI, their relevance in searching for the aetiological factors in the progress of degenerative processes remains indirect.

Surgical disc specimens and cadaveric models are unable to provide correlations between mechanical loading and the degenerative metabolic processes in the IVD.

Isolated disc cell and tissue cultures as well as animal IVDs allow for studying the effect of loads and strains on metabolic cell response. No conclusions can be made in analyzing the evolution of the degenerative processes.

Based on the observation that during aging and degenerative processes, the ECM of the IVD loses water and becomes stiffer as the NP increases its collagen content, a variety of mathematical models of intervertebral discs simulating the different stages in the progressing degenerative process is developed. Studying such IVDs as biomechanical entities has major advantages in predicting mechanical behaviors of the IVD when it is subjected to various loading conditions. Using numerical models, introduction of changes in the human IVD physics such as geometry, volumetric changes, fluid flows and fluid pressures, porosity, osmotic pressure effects, permeability, deformations in tension, compression, or shearing configurations, electric streaming potentials, … can be reproduced mathematically. The influences of mode, magnitude, frequency, and duration of different mechanical loading patterns of compression, tension and shear onto the ECM can then selectively be analyzed to understand the potential of important regulators and inhibitors of metabolism of the IVD cells and the evolution to IVD degeneration.

However, each of these study models will retain its shortcomings. Indeed, a long way to the development of an innovative biological treatment annihilating the disasters of fusion surgeries.

13. Hypermobility of degenerative spinal segment

During the degenerative processes, the IVD shows displacement of the centrodes of motion resulting in a reduction of flexion-extension but an increase of its rotation. The functional spinal motion segment becomes more wobbly which is typically encountered during spinal surgery. However, the FSU is by no means a hypermobile intervertebral segment associated with or synonymous of an increase in quantitative ROM in vivo (flexion, extension, lateroflexion, rotation). See below: ‘IVD impairment by non-physiological motion and deprivation of motion’. Why then surgically destroying a segment which mother Nature can stabilise overtime? Why not looking for methods which mother Nature uses for ages?

14. ‘Clinical’ spinal instability does not exist

For totally unknown and for scientifically completely incorrect reasons a temporary segmental intervertebral hypermobility (and a variable pattern of painful symptoms) has been translated with the incorrect and ambiguous clinical wording of ‘spinal instability’. Although ‘spinal instability’ only can be created in a laboratory (Wiltse; White & Panjabi; Shirazi-Adl) and cannot be seen in the living human individual, some surgical clinicians, who do not understand the biomechanics of the lumbar spine and who never examined lumbar spines at the autopsy table, are excited by using this term for convincing their patients to implant one of the hundreds existing and sometimes funny fusion systems (Al-Rawahi; Ashton-Miller; Kirkaldy-Willis*; Mulholland). One advice to all my colleagues: just try these ‘things’ on a postmortem lumbar spine and analyse the resulting fusion yourself. The author was consultant for two implant companies but only for a very short time. For him the basic saying ‘don’t harm the patient’ still has a value.

The wrong interpretation of the biomechanical term ‘spinal instability’ for the degenerative discogenic syndromes opened the doors for a financially rewarding fusion business industry. Just think of the huge potential market as 80 % of all low back pain patients suffer degenerative discogenic syndromes. Millions of low back pain patients, who suffered signs and symptoms of this syndrome, are now continuously experiencing the painful and sometimes agonising and invalidating consequences of this business guided surgical industry treating a non-fatal clinical entity.

‘Spinal instability’ is a definition used only for patients suffering pain associated with mobile vertebral fracture fragments related to a traumatic or oncologic vertebral fracture. It is evident that these unlucky patients may require rigid stabilising procedures.

*According to the degenerative cascade proposed by Kirkaldy-Willis (and Farfan), degeneration increases the spinal segment progress from dysfunction to an instability phase (but what’s that?), and finally to a restabilisation phase. Although cadaveric studies have confirmed that segmental motion tends to increase with increasing severity of disc degeneration (= hypermobility!), a decrease in segmental motion has been found at the highest grade of degeneration.

15. Animal models are extremely important

Animal models are extremely important in further analyzing the relationship between biomechanical and cellular biochemical sciences. The final goal is, one day, to develop much more efficient and innovative biologic treatment strategies for the lumbar degenerative discogenic syndrome from which over 80 % of all low back pain patients suffer.

These animal models have to target the molecular and cellular components of the IVD and as such have to neutralise the intradiscal degenerative processes in the lumbar spine (Elliott; Gruber; Mason; Moskowitz; Silberberg; Ziv). To this purpose, the development of a standardized in vivo animal model that more accurately mimics the human IVD in humans would allow for more meaningful and realistic results.

16. Humans and animals have some IVD similarities

Small and large animal models (rats, rabbits; calf, goat, minipig, primates) have different loading histories and related biologic responses (Beckstein; Henriksson; Hoogendoorn; Nuckley; Yoon).

Although sizes of the IVDs and their cell types are very different, the size, shape and structure of the lumbar IVDs of a large animal are similar to the human lumbar IV discs. Similarities regarding spinal flexibility exist. In small animals the NP contains a large number of notochordal cells. Consequently, the IVDs have a different metabolic activity. On the other hand, the characteristics of the AF in animals are not drastically different.

17. Experimental models indicate existence of mechanical damage to IVDs

Different experimental models (animal, biomechanical, mathematical) clearly indicate that normal repetitive daily compressive loading patterns (not the load transfers in shear) and abnormal ECM stresses damage the endplates, generate abnormal stresses in the NP and cause complete tears in the AF. The identified degenerative changes in animal IVDs are similar to those in human IVDs:

(1) notochordal cell loss in the NP,

(2) loss of proteoglycan and water content,

(3) decreased osmotic and hydrostatic pressure,

(4) endplate sclerosis,

(5) occurrence of degradative enzymes (MMPs), various growth factors (fibroblast growth factor FGF and transforming growth factor TGF-α) and pro-inflammatory cytokines (tumor necrosis TNF-α),

(6) reduced cell viability in the NP,

(7) increased collagen type I production and fibrocartilaginous displacement of the NP,

(8) annular delamination and infolding,

(9) temporarily segmental hypermobility (no instability!),

(10) peripheral osteophytes.

18. Primary role of lumbar IVD

The primary role of a lumbar IVD is mechanical: transferring an axial load through the distal part of the spine.

19. IVD biomechanics and (discogenic) low back pain

Understanding the mechanics (the hows) of the lumbar IVD to transfer axial load remains essential for understanding how degenerative discogenic low back pain may originate and be sustained (Mulholland).

20. Alterations in mechanical behavior affect all spinal structures

Since the IVDs occupy around one third of the length of the vertebral column, alterations in the mechanical behavior of the IVDs will affect other spinal structures such as the osseous tissue of the vertebral bodies, cartilaginous tissue of the zygapophyseal facetal joints (ZGA), muscles and ligaments. Indeed, and except due to direct traumatic accidents, ZGA joint degeneration always is the consequence of intradiscal mechanical changes followed by degenerative changes.

However, some tissues will adapt faster than others to loading. Related to their blood supply, muscles adapt faster than bones. The cartilaginous tissues of the ZGAs and the IVDs are the least adapting tissues.

21. Functional behavior of lumbar IVD requires mechanical interplay between EPs, NP, and AF

The biomechanical behavior of a healthy IVD requires the critical mechanical interplay between endplates, NP and AF. The relatively impermeable cartilaginous endplates allow load transfer uniformly across the AF and NP (Adams; Goel).

The unique combination of the distinct biochemical and biomechanical properties of NP and AF allows the IVD to absorb and disperse the daily loading compressive forces experienced by the lumbar spine. The molecular meshwork of the proteoglycan-rich NP, entrapped in the highly organised collagenous-rich AF, uniformly translates the compressive loads into a hydrostatic pressure in the isotropic* (McNally) and semifluid gelatinous NP mass. The high nuclear hydrostatic pressure is uniformly propagated but resisted as well by the peripheral and predominantly tensile resisting fibrocartilaginous lamellar and cylindrical architecture of the AF. Becoming loaded in tension, the AF shares a significant portion of compressive load on the NP (Fig. 21).

Fig. 21. Fluid pump mechanism of an intact and healthy lumbar intervertebral disc. Compressive forces on the nucleus are due to the impact of body weight, daily activities and muscle contractions. Because water is not compressible, continuous variations in hydrostatic pressure result. To resist and neutralise these nuclear compressive stresses, equal tension stresses need to be generated in the laminar structures of the annulus. When this mechanical compensation mechanism starts failing, the annulus starts fissuring in an in-to-out direction (Illustration by Jasper Baeke).

* ‘Isotropic’ means that the NP behaves as a fluid because the stress is equal in all vertical en horizontal directions

22. Functional behavior of NP. Incompressibility of water & viscoelastic dissipation

The water-filled NP of a healthy IVD is trapped between the relatively impermeable cartilage endplates and the AF. The central structure acts like a nearly incompressible viscid fluid under loading conditions but also exhibits considerable elastic rebound, assuming its original physical state upon release.

The compressibility of the NP is governed by a high concentration of negatively charged proteoglycans which attract and retain water. As water cannot be compressed, the NP will experience fluid pressurisation as a mechanism to balance the high external loads on the IVD, and to support and transfer these loads. Under various mechanical loading conditions, fluid shifts within the IVD and fluid leaks from the NP occur which change the fluid volume of the NP.

Because of this swelling pressure mechanism, axial loads applied to a healthy IVD increase the hydrostatic and osmotic pressures (see below) inside the IVDs. The axial forces are distributed equally in all directions from within the NP. This in turn will increase the tensile stresses in the AF. The pressure in the NP causes the lamellae of the viscoelastic outer AF to bulge outward (especially in the posterolateral corner), stretching the fibers in the AF (Fig. 22).

In other words, the swelling pressure of the NP is resisted by tension in the type I collagen fibers of the AF. By resisting radial stress, tension increases in the annular fibers preventing the IVD from swelling freely. At rest, the balance between the swelling pressure in the NP and the tension in the AF maintains the distance between adjacent vertebral bodies.

The viscoelastic properties of the NP are related to the presence of viscoelastic type II collagen fibers which interact with the proteoglycan matrix and the out- and inflow of water in the IVD under different loading conditions (Adams; Botsford; Virgin).

Fig. 22. Water is incompressible. According to the hydrostatic law of Pascal, pressure on water in the disc will be transmitted equally in all directions. The lumbar intervertebral disc is submitted continuously to varying degress of compression stresses (stress = a force applied to a certain cross-sectional area of an object). In the erect position the compression stress equals around 80 kg/cm² disc tissue. In a slightly forward bending position of 10 °, the stress measures 210 kg/cm² and when we carry a load the stress is at least 350 kg/cm² (Illustration by Jasper Baeke).

Overall, the biomechanical function of the IVD relies heavily on the hydrodynamic ability of the NP to redistribute most of the axial compressive stress within the spine into radial annular stresses. During weight-bearing, spinal flexion, extension, and torsional motions, vertical compressive loads in the NP are always transferred outward in the direction of the AF. As such, the AF contributes to compressive load sharing.

23. Osmotic pressures in nucleus pulposus

Increasing mechanical compressive loading creates new and higher hydrostatic pressures in the NP forcing water from the disc. This fluid loss presents the nuclear cells with a different environment until a new osmotic equilibrium is achieved as the concentration of proteoglycans increases. Local changes in the hydration and proteoglycan concentrations (PG) in the ECM change the osmotic pressures.

In regulating their metabolic responses, IVD cells in the NP and in the AF react differently to changes in osmolarity, osmolyte transport, and ion concentrations (i.e. Ca), reflecting their different embryonic origins.

Human IVD cells, at values of osmolarities believed to be present in the IVD (~ 430 mOsm), exhibit an increased gene expression for the PGs decorin and biglycan in cells of the AF but decreased biosynthesis in the NP cells. Above or below the values of those osmolarities the IVD cells decrease the biosynthesis of PGs.

24. Biomechanical viscoelastic behavior of AF

When subjected to the compressive loads of weight-bearing and spinal motions, the IVD displacements are found to be vertical in the NP and outward in a characteristic bulging pattern that is observed through most of the AF but especially its posterolateral corners (Fig. 22).

The outward radial movement of the hydrated gel-like NP prevents the thick wall of the AF from bulging inward. The outer AF is well suited for minimizing IVD bulging and AF stresses.

The healthy AF sustains high tension loads. The capabilities of the AF to resist tensile loads and mechanical deformation (mechanical stiffness* of 5-30 MPa) depend on its lamellar and fibrocartilaginous structure containing a high concentration of type I collagens.

In response to stretch, collagen fibre sliding events arise in the successive lamellar sheets changing the tension in the AF. In the healthy IVD, this fluid-flow generated frictional dissipation mechanism not only results in the characteristic bulging and deformation pattern (= stretch) throughout the AF but keeps the AF from sagging inward and becoming more vulnerable to mechanical damage.

In compression, the AF reveals an ECM that is substantially less stiff than in tension because the collagen fibers are not loaded when the tissue is compressed.

The ECM of the cells in the AF are less resistant (0.3 MPa) to tension. Indeed, most mechanical properties for the AF vary as well among regions of the inner and outer AF in a manner that reflects their different collagen fiber organizations, protein and proteoglycan concentrations, water flow and water redistribution. These behaviours support the modelling of the AF as a fluid-filled collagen-reinforced material that exhibits anisotropic** behaviours and explain the viscoelastic behavior of the AF. For these reasons a radiological bulging cannot be explained as a ‘disc herniation’. Understanding the viscoelastic mechanism of the AF will avoid unnecessary destructive discectomies!

Overall, the IVD is capable of converting axial spinal loads into tensile hoop*** stresses (= tensile circumferential stresses) in the outer AF, while allowing motion of the vertebral segment. The surface strains are found to be tensile. Collagen type I fiber sliding occurs in response to stretch within the center of the IVD. Flexion, extension, and bending motions may produce similar but locally varying patterns of deformation.

* ‘Stiffness’ is a measure of resistance offered to external loads by a structure as it deforms

** ‘Anisotropic’ means that the NP no longer behaves as a fluid because the stress distribution is not equal in all vertical en horizontal directions

*** ‘Hoop stress’ is a stress in a pipe wall. It is represented by the forces inside a cylinder acting towards the circumference perpendicular to the length of the pipe

25. IVD continuously responds to spinal compressive forces

During normal daily activities, the lumbar spine (vertebral bone and IVDs) is constantly exposed to varying mechanical loading forces (= N) and stresses (= F/m²) not only involving compression, but torsion and vibration as well. The IVD is the major spinal load-bearing element in axial compression and flexion. In the young healthy spine, the IVD transfers ~ 80% of the compressive load applied to the motion segment (Adams).

Forces on the lumbar spine act longitudinally and as such compress the spinal segments. These compressive forces are associated with posterior muscle activity but their antagonistic abdominal muscle activity increases the compression forces (see above). Although the muscle groups seek an equilibrium, a compressive muscular effect always is present on the lumbar spine.

The compressive force on the human lumbar spine is estimated to range from 150-300 N (= 15-30 kg) during supine and recumbent postures and to 1400 N (= 140 kg) during relaxed standing with the trunk flexed 30 degrees (Fig. 25). The compressive force may be substantially larger when holding a weight in the hands in the static standing posture, and even more so during dynamic lifting (Nachemson; Sato; Schultz). In individuals with healthy IVDs, the spine sustains these loads without injury. The AF resists compression directly but indirectly as well by increasing the tension in its collagenous lamellar layers.

Fig. 25. According to the research data by professor Al Nachemson and compared to the erect position (100 %), the intervertebral discs in the lumbar spine are loaded 25 % less in the supine position. In the sitting position with a straight spine, the discs are loaded 40 % more.

 ‘Imagine a human being who has to carry weights of 60 kg the whole day! Well, each of the IVDs is subjected to forces varying from 600 Newton (~ 60 kg) in normal conditions to 2500 Newton (~ 250 kg) under maximal axial compressive load’ (White & Panjabi).

Under pure compressive and eccentric compressive loading, the healthy lumbar IVD demonstrates a uniform stress (= F/m² = N/m²) distribution across the entire endplate area. When loads increase from 250 N (= 25 kg) to 4500 N (= 450 kg) the height of a motion segment is reduced by 0,9 mm. Approximately half of the IVD height reduction can be attributed to the endplates bulging into the vertebral bodies (Brinckmann; Holmes). Compressive force of 2000 N (= 200 kg) stretches the collagen fibers in the outer AF by less than 2 % and causes the AF to bulge radially by 0.4 to 1.0 mm (Strokes).

26. Hydrostatic pressure in IVD

IVD structures (and thus NP cells) are exposed to wide ranges of intradiscal hydrostatic pressures depending on the different loading conditions and positions.

Hydrostatic pressure (= MPa) is one of the principal mechanical signals that influence IVD

matrix turnover by regulating gene expression of ECM forming proteins and ECM turnover enzymes.

Hydrostatic pressure is at its minimum during lying down (0.25MPa). This low hydrostatic pressure has no or little influence on gene expression with no or only little alterations of cellular activity. Low loads may support the maintenance of the disc ECM by maintaining the aggrecan expression and because of their minimal effect on the expression of matrix metalloproteinases.

High hydrostatic pressures (2,5 MPa) tend to decrease the gene expression of all anabolic proteins (collagens type I and II), to decrease the ECM protein expression and to increase NP cell death (apoptosis). Hydrostatic pressure is at maximum during weights lifting with a round back.

27. Compressive stiffness provided by IVD

The IVD provides most of the compressive stiffness (= F/m)* of the motion segment, whereas ligaments and ZGA facetal joints contribute significantly to resisting bending moments and axial torsion.

Mathematically, stiffness is defined as the resultant of the load applied and the displacement produced. The stiffness of intact spine motion segments has been estimated in the range of 600 to 700 N/mm in axial compression and 100 to 200 N/mm in anterior, posterior, or lateral shear, noting, however, considerable individual variation.

* stiffness is a measure of resistance offered to external loads by a structure as it deforms (=F/m)

28. IVDs have difficulties resisting loads in shear

As compared with compression, the lumbar IVDs appear less well suited to resist loading in shear. Load transfer in compression occurs via the production of high hydrostatic pressures. Load transfer in shear occurs via the AF without the development of significant IVD pressure (Frei; Tencer).

When the zygapophyseal facetal joints no longer resist the intervertebral shear stresses while a rotational movement is performed in a flexed position, the AF will generate high torsional tension leading to a tear and severe disc degeneration.

29. Deprivation of mechanical stimuli impairs IVDs. Unloading IVD

The essential homeostasis of the IVD tissue is impaired when compressive mechanical loading is lacking such as during rest, inactivity, or hypomobility and during other environments where compressive mechanical loading is removed from the IVD (spaceflight).

A reduced or lack of mechanical stimulus considerably reduces the metabolic activity of the IVD cells with resulting decrease in the proteoglycan synthesis and decrease in the transport of water, nutrients and metabolites through the endplates. Depending on the age of the IVD, the NP may well swell to +/- 200 % of its initial volume and develop a very high hydrostatic pressure.

In circumstances of IVD immobility and ‘hypoloading’ most individuals will develop low back pain. In order to avoid IVD lesions, astronauts and cosmonauts need to load their IVDs gradually from a recumbent to an upright position. Further complete lack of neuromuscular control of their trunk muscles (see above) as well as the potential presence of unfavourable genetic inheritance only can accentuate their symptoms.

30. IVD impairment by non-physiological motion and deprivation of motion

Physiological motions, load distributions, and intradiscal osmotic and hydrostatic pressures are mandatory for IVD viability.

 An IVD environment that is deprived of normal motion impairs the maintenance of IVD tissue homeostasis (Stokes, Iatridis 2004). It is well known that the progressive degeneration of the aging lumbar IVDs is accompanied by non-physiological motion patterns.

Moderate IVD degeneration with radial tears of the AF causes temporary hypermobility of the spinal segments. These lumbar intervertebral degenerative hypermobilities (not those related to spinal fractures) are much more complex than medical logic suggests. Huge kinetic differences beyond normal are found related to the interplay between the geometry of the IVD, its degree of degenerative fragmentation, the vertebral bony constraints, and competence of the ZGA facetal joints. Segmental hypermobility changes compressive loads, axial translations and rotations, anterior shear loads and translations, and the flexion, rotation, torsional and extension movements. If the hypermobility cannot be sufficiently neutralised by muscles and ligaments, loss of spinal balance and lordosis are resultant problems.

Progressing degenerative processes induce a reduction of the intervertebral motions rather than an increase in mobility that would be expected if the process led to instability (Sengupta; Fujiwara). In the advanced degenerative phases with disc space collapse and osteophyte formation, the motion segment ultimately becomes less mobile until spontaneous fusion occurs.

31. Compressive vs distractive effects on degenerating IVD

Since a degenerating IVD can as yet not be repaired nor regenerate itself, external devices may provide conditions for biological attempts of restoration.

In animal studies, surgical compressive devices, static or dynamic, reduce the intradiscal hydrostatic pressures significantly leading to a further decrease of IVD height, disorganization of annulus architecture, and increased cell apoptosis in the AF and cartilaginous endplates. Interestingly, these changes are reversible to a certain extend when distraction is applied following a period of compression.

Theoretically, the easiest way to restore the IVD height is distraction, but little is known regarding its biomechanical and biological effects on IVD tissue in human IVDs. Animal studies indicate an increase of intradiscal hydrostatic pressure values in the NP and less degradation of the collagens. But concluding that axial distraction devices will spontaneously induce IVD restoration is too optimistic because such enthusiastic results have never been registered in distracting human degenerating IVDs.

Non-physiological rigid compressive and immobilizing devices as well as mobile distracting devices do not create suitable intradiscal environments for future innovative IVD-stabilizing procedures like stem cell therapy, growth factor applications, and gene transfers.

32. Effect of normal loading patterns on IVD

A physiologic threshold of compressive loads, hydrostatic and osmotic pressures is essential for the IVD cells to maintain their phenotype and for the healthy IVD to synthesize and maintain its biochemical composition, structure and mechanical properties.

Normal or moderate physiological compressive loading conditions trigger IVD cell metabolism. Nuclear cells exposed to hydrostatic pressures of around 3.0 MPa directly induce anabolic responses such as an elevated extracellular matrix protein gene expression for encoding the major ECM proteins (type II collagens and aggrecan), increase the production of TIMP-1 (tissue inhibitor of metalloproteinases-1) and decrease the production of degradative matrix metalloproteinases (MMPs) in the NP. Cells of the AF seem to be less responsive to compression than the nuclear cells. AF cells react to tension stresses.

However and overtime, the normal cycle of IVD deformation and recovery caused by normal routine daily activity eventually leads to fatigue failure of the NP and the AF (Buckwalter).

33. ‘Excessive’ IVD loading patterns

Mechanical studies indicate that IVD ruptures and their further progression into a degenerative cascade can only occur when IVD overloading is also involved (Stokes; Iatridis).

Repetitive, sustained and excessively high compressive mechanical load conditions on the IVD tissues (3 to 5 MPa hydrostatic pressures) create a detrimental environment for IVD cells, chemically degrade the ECM and lead to morphological degenerative IVD tissue changes. The extent of these degenerative changes depends on the characteristics of the stimuli such as loading mode, magnitude, duration and frequency of load and pressure (Handa, Neufeld).

Compressive overload conditions induce  IVD cell death (apoptosis), decrease the matrix aggrecan-gene expression, activate the catabolic genes for increasing the degrading matrix metalloproteinases (MMPs) and cytokine production (Handa), decrease the water content, decrease the gene expression for type II collagen synthesis and increase the collagen type I production.

Thus, a demanding mechanical environment alters the biochemical composition of the IVD. These alterations will result in micro- and macroscopic structural changes of the nuclear, annular and endplate architecture (Fig. 33). The produced localised injury evolves to such an extent that accumulation of IVD tissues microdamage outpaces the ability of the IVD to repair itself due to the slow rate of turnover and biologic repair by its cells.

Fig. 33. (1) In an intact and well hydrated lumbar intervertebral disc the compressive forces are transduced in equal tension forces in the annulus. (2) When the nucleus ages, the annulus is submitted to much greater tension forces initiating in-to-out annular ruptures. (3) Once the disc degenerates, the nucleus starts fragmenting and complete ruptures appear in the annulus. Now, compressive forces may push part of the degenerated nucleus into the spinal canal through the ruptured annulus (= the herniating process) (Illustration by Jasper Baele).

In experimental models, the IVD fails at the level of the endplates before failure propagates to the NP and the AF. The disc failures are visible as internal nuclear disc ruptures, failures of the annular collagen fibers, separation of the annular collagenous layers (= annular delamination), formation of radial and circumferential annular tears, and disc herniations.

34. Different positional loading patterns.  Standing, sitting, bending, hyperflexion

When stressed in response to the different spinal loading patterns; large changes in hydration take place in the ECM of the NP with the nuclear cells constantly experiencing hydrostatic loads.

The lowest hydrostatic pressures at rest are estimated at approximately 1 to 3 atmospheres or 0,1 to 0,3 MPa and increasing 2- to 3-fold during activities such as standing upright and sitting.

The highest hydrostatic pressure (10 to 30 atm or 1 to 3 MPa) occurs under more extreme loading conditions when leaning forward and lifting heavy weight.

As a consequence of the normal diurnal*-nocturnal** loading cycle the ECM of the NP loses and regains around 20-25% of its fluid over 24 hours.

STANDING.

In 1962, Naylor already stressed that mechanical stresses (stress = F/m²) placed upon the IVD by the upright posture weakens the structure of the IVD. Indeed, static compressive loads inhibit cells and degrades ECM by producing degrading enzymes (Ching). Standing erect puts approximately 500 N of compressive force on the lumbar spine. In the healthy IVDs, these high compressive loads are supported through the high swelling pressure related to the large concentration of proteoglycans and fluid in the ECM of the NP.

PROLONGED SITTING

Prolonged sitting results in sustained axial compressive loading which alters the viscoelastic properties of the IVD and the vertebra (Goel; Keller). The NP needs to transfer the axial loads into radial tension in the AF. How does it work? The NP in the intact or in slightly degenerated IVDs acts like a gelatinous mass. A compressive load decreases the volume of the gelatinous nuclear mass with resulting decrease in IVD height. As water is non-compressible, this also increases the hydrostatic pressure which leads to bulging of the outer AF. During the day, compressive loads reduce the IVD height mainly because of water being squeezed out of the IVD, and in part due to the creep of the viscoelastic annulus collagen fibers. Both effects are reversible in healthy IV-discs while unloading of the spine during a night's bed rest.

BENDING FORWARD

Bending forward to lift 10 kg puts approximately 2000 N on the IVD. Animal experiments analysing static bending stresses on mouse tails result in increased cell death, a down-regulation of collagen II and aggrecan gene expression, and disorganization of the AF.

HYPERFLEXION

IVD cells are sensitive to mechanical stimuli (compression, pressure, stress, strain) and subsequent changes in hydrostatic pressure and osmotic pressure. It is known that hyperflexion can directly damage the three components of the IVD. Lifting quickly (speed of loading) can increase spinal loading by > 100 % (Dolan). This leads to fissures in the endplate and/or a decreased swelling pressure in the NP and/or failure of the tension strength of the AF. All three elements induce discogenic degenerative processes. Compression combined with repetitive flexion and extension causes disc herniation in an experimental porcine model. In the laboratory, disc herniation could be provoked even in young and healthy animals (Callaghan, McGill 2001). It is likely that in an moderate degenerative IVD, compression together with repetitive motion can cause similar effects.

* diurnal cycle = vertical posture, increased pressure forces water and waste out of disc, disc thickness decreases

** nocturnal cycle = horizontal posture, water and nutrients move into disc, thickness increases

35. Vibration as loading mechanism

Vibration as experienced by drivers (trucks, buses, tractors, rallies, heavy machinery) as well as by helicopters pilots is a well-known factor causing low back pain. Although this loading pattern may adversely affect nutrition and metabolism of the IVD, vibration has till now never been associated with IVD degeneration.

36. Loading scoliotic IVDs

Biological and biochemical analyses of human scoliotic IVDs indicate that alterations in mechanical loading and motion patterns generate changes in the macrostructure as well as in the biochemical composition of the disc.

The tissue of the IVD in the apex of the scoliotic curves is severely deformed due to its asymmetrical mechanical loading. Calcification of the endplates occurs at a much younger age in life limiting the nutrient transport from the vertebral body into the IVD and causing cell death. In the NP of these apical IVD cells the level of oxygen and the viability of the IVD cells are much lower than in the other discs. On the convex side of the scoliotic curve there is an increase of the ECM proteoglycan synthesis and on the concave side the cells of the AF follow Wolff's Law as the total collagen concentration and especially the expression of collagen type-I increase.

37. Altered IVD loading in fused and adjacent fused spinal segments

When a degenerative and hypermobile (incorrectly and ambiguously called ‘unstable’) lumbar spine is stabilized (= fusion) with anterior, lateral, posterior, or combined antero-posterior instrumentation, the operated intervertebral discogenic motion segment(s) should be entirely immobilized. At least this is the aim.

The loss of mobility at the fused level(s) then needs to be compensated in one way or the other by ‘forcing’ the adjacent levels into more flexion, extension and torsion. Adjacent intervertebral disc levels experience changing hydrostatic pressures and higher tensile and shear deformations (LI; McNally; Mimura; Schizas; Shirazi-Adl; Wang). The biologic expression of the subsequent altered loading patterns, radiologically visible as the initiation or acceleration of IVD narrowing and osteophytes, has been investigated in small animal hypermobility models. They demonstrate identical biologic annular degradative findings in the AF as found during sustained compression.

Although it still remains impossible in humans to differentiate the natural occurring degenerative intradiscal phenomena induced by genetic predisposition from those induced by a changed mechanical loading pattern, it seems very likely that the creation of intradiscal hypo- or hypermobility and/or an increase (adjacent to a fusion) or decrease (included in the fusion) of the intradiscal hydrostatic pressure and intradiscal strains are responsible for inducing changes in the surrounding ECM and the IVD cells. Indeed, animal models of fused spines indicate that the proteoglycan synthesis and the hydration in the NP decrease.

38. Complex but precarious balance and interplay between biologic and biomechanical influences

In 1962, Naylor already indicated that a series of biochemical processes independently weaken the structure of the IVD which will ultimately decompensate when subjected to biomechanical stress. Over the following decades, in vivo and in vitro mechanobiologic studies clearly confirmed that mechanical factors influence the biosynthetic activity of IVD cells. However, this interference partly explains the occurrence of the degenerative processes in the aging IVD.

The balance between the biological structure and the biomechanical function of the IVD is precarious, meaning that the potential development of IVD degeneration mainly is predisposed by genetic factors and modulated by mechanical influences. Indeed, the repetitive lifetime daily physical environmental exposures of the spine trigger the expression of available unfavourable genes to tip the balance toward accelerated IVD degeneration. Genetics influence the quality of the tissue material which has direct mechanical consequences.

The influence of socioeconomic environmental factors in the evolution of this degenerative process clearly is overestimated.

39. Cells recognise different daily  mechanical loading patterns

The lumbar intervertebral joint is a complex organ where the IVD cells in its cartilaginous architecture continuously respond to the stress of daily mechanically induced compressive, tensile, and shear deformations (= strains) of their extracellular matrix. This phenomenon is called cellular mechanical signal transduction or mechanotransduction.

IVDs are loaded throughout life, but can withstand most pressures normally. The duration, magnitude, frequency and type of loads influence the hydrostatic and osmotic pressures in ECM. The IVD cell metabolism, responsible for the synthesis of the molecular components (especially collagens and proteoglycans) of the IVD, reacts very sensitively to such pressure changes. The IVD tissue can remodel reversible microchanges but irreversible changes may remain and initiate IVD degeneration.

Regions of the IVDs experiencing high levels of compression like the ECM and the cells of the gelatinous NP will respond differently than the same structures in the fibrocartilaginous AF. When a compressive stress (stress = F/m²) is applied to the IVD and starts exceeding the swelling pressure, only the nuclear cells will be responsive to pressurization and not the cells of the AF, reflecting their different embryonic origins. The cells in the outer AF mostly react to stretch.

40. Mechanical loads influence anabolic and catabolic functions of IVD cells

The mechanobiologic view of the spine indicates that the anabolic and catabolic functions of the IVD cells are influenced by alterations in mechanical intervertebral joint-loading conditions exerted on their extracellular matrices. The mechanical and biologic factors interact to define whether the IVD tissue remains in homeostasis, accumulates damage, or otherwise remodels in response to the different loading conditions. Sato described this phenomena as ‘adaptive remodelling’. Cells ‘adapt’ to normal loads maintaining a balance between anabolic* and catabolic** mechanisms. The IVD cells ‘adapt’ to abnormal low and high loads by stimulating the destructive metabolism (by the MMPs and cytokines).

The key regulators of these mechanobiologic responses for IVD cells are the mechanical stimuli experienced at the cellular level which are different from those measured for the ECM. Any change in mechanical load distribution on the IVD has an impact on the ECM as well as on cell viability. Changes in stresses and strains in the ECM, related to varying compression loads, fluid volume, fluid pressures, fluid shear stress, longitudinal stretch, bending etcetera are continuously sensed by the mechanoreceptors on the cell surfaces which modulate cell-cell and cell-matrix interactions.

* Anabolic means up-regulation of all anabolic genes and of proteins and down-regulation of destructive enzymes

** Catabolic reactions stand for down-regulation of proteins and up-regulation of the degrading metalloproteinases (MMPs) and cytokines

41. Mechanism of cellular mechanical  signal transduction (mechanotransduction)

The mechanical loading variations in the ECM during standing, sitting, bending and resting are translated into adaptive changes in cell proliferation and cellular biosynthetic activity. These cells adapt and alter the production of the different molecular components (proteoglycans, collagens) in their ECM which are responsible for maintaining and repairing the IVD to give the disc its structural and functional integrity. Because of the low cell density and lack of blood supply, adaptive cellular changes are not as efficient as the reactions by bone cells in the vertebrae.

The annular cells with their longest axes aligned parallel to the oriented type-I collagen fibers within the lamellae and with processes into the matrix of the lamellae respond differently to the varying loading stimuli than rounded chondrocyte-like cells which in the mature nucleus extend small processes into the matrix.

During compressive axial strain, the rounded cells embedded within the ECM of the NP experience high hydrostatic and osmotic pressures but virtually no volume change. Both compressive and tensile strains remain quite small. For all times, NP cells experience tensile transverse strains and compressive axial strains that are much smaller than those of the surrounding matrix.

In contrast, in the anisotropic matrices of the AF the highly oriented elongated cells within the lamellae are well adapted to experience tensile strains matched to those of the ECM and associated volumetric changes in response to this tensile loading. The transverse compressive strains within the AF cells are substantially higher (2 to 5 times) than the surrounding ECM values.

Reorganisation of the cytoskeleton of the IVD cell in response to mechanical stimulation signals and activates mechanosensitive biochemical pathways (mitogen-activated protein [MAP] kinase and NF-kappa β pathways) and transcription factors (EGR-1 or Sox 9 critical for chondrocyte differentiation), upregulates mRNA and changes gene expression by binding to ECM promoter-gene expression (i.e. tenascin-C and collagen XII gene promoters contain sequences that respond to stretch).

Once certain threshold levels of strain and stress have been exceeded,  gene expression for degradative enzymes (MMPs) is turned on.

42. Possible existence of a ‘mechanostat’

The ability of the IVD cells to react appropriately to a large variety of biomechanical loading stimuli depends on the presence of their EC matrix, their intact cytoskeleton and cytoskeletal tension. It is possible that some kind of ‘mechanostat’ (referring to a thermostat at home) may exist as well to regulate the cytoskeletal internal tension in response to the varying external cell-matrix interactions. Indeed, integrins (= special cell-surface receptors that recognize particular ECM proteins) sense the cell-matrix variations and interact with the internal tension.

43. Mechanotransduction significantly varies with genotype

All cartilaginous cells, those of the IVDs as well as those of the peripheral joints, remain responsive to physical stimuli hereby enhancing their biosynthetic EC matrix synthesis. However, this cellular mechanotransduction varies significantly with genotype as individuals respond very differently to mechanical loading patterns than others do.

44. Biomechanics and degeneration

of lumbar IVD

The normal development of the lumbar IVD is influenced both by genetic factors and by the mechanical loading environment. Degeneration of the IVD is governed by a complex interaction between familial and especially genetic inheritance, aging processes*, declining IVD nutrition**, and all types of daily and/or repeated mechanical loading stimuli (compression, tension, stretch, strains, fluid shear stress, etc.) leading to an interference with the biochemistry inside the normal biologic aging IVD (Adams; Buckwalter; Horner; Nachemson).

The IVD cells no longer are able to maintain a chemically appropriate and structurally intact ECM. The extent of the ensuing degenerative changes in the IVD material (nuclear disintegration and fissures and/or ruptures in the endplates and/or annulus fibrosus) depends on mechanical factors (the magnitude, duration and frequency of load and pressures).

Whatever the extend, the alterations alter substantially the further mechanical function of the ECM. Degenerated IVDs demonstrate an uniform stress distribution under pure compressive loading, but show a non-uniform stress distribution eccentric compressive loading. The asymmetric stress distribution is presumed to occur because of the relatively solid but increasing fragmentation of the degenerating NP and its inability to conform to the eccentric loads. This may lead to the occurrence of acute attacks of low back pain (Mulholland) and the further development of the degenerative discogenic syndrome (DDS) responsible for LBP in 70 % to 80 % in the world (Fig. 44).

Fig. 44. The degenerative alterations in the IVD material (nuclear disintegration and fissures and/or ruptures in the endplates and/or annulus fibrosus) substantially alter the further mechanical function of the IVD. The increasing fragmentation is presumed responsible for asymmetric stress distribution. According to professor Bob Mulholland, this lead to the occurrence of acute attacks of low back pain. A degenerative discogenic syndrome (DDS) may ensue.

(A90-139 / Declerck & Kakulas, Neuropathology, Perth, Western Australia).

* see topic: ‘Lumbar Disc Extracellular Matrix’

** see topic: ‘Lumbar Disc Nutrition’

45. Biomechanics and degeneration of nucleus pulposus

The efficient functioning of the lumbar IVD depends largely on the physical properties of the NP which in turn are closely related to its proteoglycan structure and content and their water-binding capacity.

While aging, water is continuously lost because the amount of proteoglycan progressively decreases. The IVDs gradually change from a hydrostatic to a more solid behavior. A higher production of coarse collagen type 1 fibers rather than fine type 2 fibrils results in a transition to a more fibrous structure.

Due to the progressing reduction of the hydrostatic (swelling) pressure, the ECM experiences lower magnitudes of transverse tensile strain due to an increasing shear stiffness.

Aging IVDs gradually become less resistant to compressive loads as well and no longer are capable of normal absorption and redistribution of the stresses placed upon them. Abnormal stresses are generated in their ECM which cause the cells to experience substantially higher compressive and tensile strains which in turn induce a reduced cell viability in the NP and stimulate the IVD to degeneration.

In those with unfavourable genes, lifelong continuous cyclic and repetitive mechanical loading from all daily positions and activities - and more than from heavy physical activities related to work and leisure - will trigger the onset for developing and accumulating degenerative damages in the ECM of the disc cells.

The most dramatic changes in the NP of the IVD with degeneration are the changes in the micromechanical factors: changes in cell volume (hydration), the loss of fluid pressurization, variations in cell pressure, cell deformations, fluid-flows in the vicinity of the cell. These changes must be the key regulators of the responses of the IVD cells to the applied loads resulting in an altered biochemical composition, structure and mechanics of the ECM.

Note: intradiscal nuclear degeneration is much more common in the lowest two L4-L5 and L5-S1 levels. In the upper L1-L2 and L2-L3 IVDs, the degenerative effects are rather seen in the endplates.

46. Biomechanics and degeneration of endplates and annulus fibrosus

A degenerating lumbar IVD results in altered transmission of forces across the endplates and the NP with a resultant increase in the stress experienced by the AF. These biomechanical phenomena finally not only give rise to fissures in the endplates and in-to-out disruptions in the AF but microtraumata as well at the level where the AF fibers insert into the vertebral bone (rim lesions). The increased stresses are posture dependent which is postulated to be the cause of acute low back pain attacks (Mulholland; Sengupta).

Endplates

An endplate of the lumbar IVD is the first component to fail when subjected to loading. Inappropriate loads lead to endplate fractures. Disc fluid is pushed into the adjacent subchondral vertebral bone causing an edematous reaction which is recognised on MRI by the occurrence of a Modic sign.

The distribution of mechanical stresses across the vertebral endplates and subsequently across the IVD depends on the degree of existing aging and degenerative processes in the NP. On the other hand, the degenerative processes in the IVD are accelerated whenever a mechanical loading causes defects in the endplate.

Annulus fibrosus

The processes of IVD tissue aging and degeneration (breakdown of ECM, less proteoglycan synthesis, more type I collagen production, apoptotic cell loss and formation of cell clusters) extend from the NP to the AF. Water loss and subsequent depressurisation in the NP (= decompression) gradually generate less tensile stresses in the AF to maintain IVD height but start concentrating compressive stresses to transmit load.

High compressive stresses induce a form of annular wall microdamage that is widely disseminated through its complex collagenous architecture. The compressive stresses progress from the inner to the outer regions of the AF. They mostly arise in the posterior AF which separate the adjacent lamellae (delamination) appearing as concentric tears in the AF. Because the AF in the older IVDs has to resist the compressive loads more and more, the annular wall gradually collapses. The annular height starts decreasing. As a result the outer lamellae fold outwards (bulging) and the inner lamellae buckle inwards (Adams; Schmorl; Yu) (Fig. 46).

Fig. 46. High compressive stresses induce annular wall microdamage which progresses from the inner to the outer regions of the AF. The annular wall gradually collapses. As a result the outer lamellae fold outwards (bulging) and the inner lamellae buckle inwards.

(X83-593 - Declerck, Taylor, Kakulas, Neuropathology, Perth, Western Australia).

Identical physical alterations in the AF are less dramatic than in the NP but definitely more harmful. The AF is better vascularized and contains a higher cellularity, and therefore able to better withstand the mechanical loads. With aging and degeneration, loss of ECM hydration and changes in collagen structure (more collagen type II production) contribute to further increases in compression (the compressive modulus of the AF approximately doubles), to slight increases of the shear modulus, and to some alterations in tensile properties. The degenerating AF becomes more permeable as well to fluid-flow in all directions except in inner-outer directions, reflecting an altered porosity due to degeneration. The occurrence of the consequential structural changes can be responsible for painful discogenic expressions.

47. Biomechanics and potential pain production

No doubt there exists an interplay of both biochemical and biomechanical factors in the degenerating lumbar IVDs.

The occurrence of degenerative structural failures in the endplates and in the AF (Adams; Crock) may in the long term be responsible for creating pain-signaling pathways responsible for painful discogenic conditions which finally may result in the clinical features of the degenerative discogenic syndrome. Indeed, it is well known that In degenerating discs of patients suffering low back pain the hydrostatic pressurization is significantly reduced compared with that of normal discs. Hence the importance of pressure evaluations during discography.

48. Conclusion by the author

In order to understand the huge amount of failures in lumbar fusion surgeries for the degenerative discogenic syndrome, representing over 80 % of all chronic low back pain sufferers in the world, it is primordial to understand the relationship between the biology and the mechanics of the intervertebral disc. However, it remains a highly complicated matter.

Genetics and mechanical conditions predispose the aging IVD to the development of a variety of small degenerative lesions (endplate fissures and ruptures, internal disc rupture, fissures, tears and delamination of the annulus ...) to such an extent that these structural degenerative changes become painful and symptomatic. And because of its slow turnover, the IVD has no healing potential.

The stabilisation or the potential of restoration of a lumbar degenerating IVD must be based on an understanding of the actual knowledge of ‘spinal’ mechanobiology. A basic insight in the interrelated mechanisms is essential to appreciate the innovative ideas for developing a lumbar spinal re-loading device in association with an intradiscal cell or molecular based therapy.

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