do intervertebral discs deserve their bad reputation?

DO INTERVERTEBRAL DISCS DESERVE THEIR BAD REPUTATION?

Joseph A. Buckwalter, MS, MD

Intervertebral discs are a critical component of theaxial skeleton. They stabilize and maintain the align-ment of the spine by anchoring adjacent vertebral bod-ies to each other (Figure 1). At the same time, theyallow the movement between vertebrae that gives thespine its flexibility, and they absorb and distribute loadsapplied to the spine. Despite these fundamental contri-butions to the function of the musculoskeletal system,they have a bad reputation. Few people who havereached or passed middle age have not experienced atleast some back pain and stiffness; both patients andphysicians commonly blame "bad discs," "degenerateddiscs" and "slipped discs" for these problems. Althoughintervertebral discs can be held responsible for theherniations of disc tissue that cause leg or arm painand neurologic deficits, do they deserve the blame forthe far more common problems of back stiffness andpain? The answer to this question lies in understandinghow intervertebral disc structure, composition and func-tion change with age and disc degeneration.

STRUCTURE AND COMPOSMHONThree concentrically arranged component tissues

form the normal human intervertebral disc: 1) the outerannulus fibrosus, a narrow ring of highly orienteddensely packed collagen fibril lamellae, includng col-lagen fibrils that insert into the vertebral bodies, 2) thelarger fibrocartilagenous inner annulus fibrosus consist-ing of a less dense collagenous matrix that lacks thelamellar organization of the outer annulus, and 3) thecentral nucleus pulposus7. Vertebral endplates, initiallyconsisting of hyaline cartilage and later of calcified car-tilage and bone, form the superior and inferior bound-aries of the discs (Figure 2).The cells of the cartilage endplates resemble

chondrocytes found in other hyaline cartilages. Theouter annulus contains fibroblast or fibrocyte like cellswhile the inner annulus and transition zone contain cellsthat more closely resemble chondrocytes7. Initially, thenucleus pulposus contains a syncytium of notochordalcells (Figure 3, Top). During growth and development,notochordal cells appear to separate from the syncytium

Figure 1. Drawing ofthe human spine byVesalius (1543). Vesaliusshowed how the intervertebral discs unite the vertebral bodies toform the central column of the axial skeleton and iliustrated thedifferences in the sizes of the intervertebral discs.

Please address correspondence to Joseph A. Buckwalter, 01013Pappajohn Pavilion, Department of Orthopaedics, University ofIowa College of Medicine, Iowa City, IA 52242, Phone (319) 356-2595, FAX (319) 356-8999, email ([email protected])

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Figure 2. Schematic drawing of the intervertebral disc componenttissues: the lamellae of the outer annulus fibrosus (OA), the innerfibrocartilagenous annulus fibrosus (IA) and the central nucleuspulposus (NP). Cartilage end plates (CEP) cover the superior andinferior surfaces of the intervertebral discs.

3. MIDDLE ` 7%

Figure 3. Electron micrographs showing viable cells from humannucleus pulposus. Top: Notochordal cells from a newborn. Noticethe interdigitation of the cell membranes and the regions of extra-cellular matrix surrounded by cell membranes. Middle: Chondro-cyte like cell from a fourteen month old infant. U indicates lipiddeposits and the arrows mark the edges of accumulated granularpericellular material. Bottom: Chondrocyte like cell from a ninety-one year old. Go indicates Golgi membranes, G indicates glycogenand arrows mark the edges of the accumulated granular pericellu-lar material. Notice the increased density of the granular materialin the matrix in the tissue from the older individual.

2 The Iowa Orthopaedic Journal

Do Intervertebral Discs Deserve Their Bad Reputation?

and then disappear completely by early adult life, leav-ing scattered chondrocyte like cells in their place (Fig-ure 3, Middle and Bottom)72829.The intervertebral disc extracellular matrix macro-

molecular framework consists primarily of collagens andproteoglycans3"1822. Collagens give disc tissues their formand tensile strength; proteoglycans, through their in-teractions with water, give the tissues stiffness, resis-tance to compression and viscoelasticity. The matricesof disc components differ significantly in their relativeamounts of these two structural macromolecules718.Collagens account for as much as 70% of the dry weightof the outer annulus, but less than 20% of the dry weightof the central nucleus in children and young adults. Incontrast, proteoglycans account for only a few percentof the dry weight of the outer annulus, but as much as50% of the dry weight of the nucleus of a child.The matrices of the disc components also vary in

the types of collagens that form part of their macromo-lecular framework18. The dense fibrous matrix of theouter annulus consists primarily of type I collagen,which accounts for about 80% of the total collagen ofthis tissue, along with small amounts of type V collagen,which accounts for about 3% of the total collagen of thistissue. Inside this region, the concentrations of type IIcollagen and proteoglycan progressively increase to-ward the center of the disc as the concentration of typeI collagen falls. In the nucleus, the concentration of typeII collagen reaches 80% of the total collagen and type Icollagen is absent. The nucleus also contains smallamounts of type XI collagen, about 3%, and both annu-lus and nucleus contain small amounts, probably lessthan 2%, of type IX collagen. Discs contain remarkablyhigh concentrations of type VI collagen, about 10% inthe annulus and 15% or more in the nucleus. This col-lagen consists of fine filaments connected to dense trans-verse bands with central lucent areas'0. Its function re-mains unknown, but its unusually high concentrationin the disc suggests that it has a role in providing theunique mechanical properties of the disc matrix.

Proteoglycan aggregates consisting of centralhyaluronan filaments and multiple attached aggrecanmolecules exist in all the component tissues of newbornand infant discs12-'4. Link proteins, small proteins thatbind to aggrecan molecules and hyaluronan, stabilizethe large aggregates. The annulus and cartilageendplate contain aggregates that closely resemble thosefound in articular cartilage; but, even in discs from in-fants, nucleus pulposus aggregates are smaller, and theirconcentration rapidly declines with increasing age12-14.In addition, with increasing age the proportion of non-aggregated proteoglycans progressively increases andthe size of the aggrecan molecules decreases dramati-

cally, especially in the nucleus pulposus'2-'4. These ex-tensive alterations in proteoglycan structure begin earlyin life, years before the age related changes in discmorphology or the development of disc degeneration.A variety of non-collagenous proteins and small

amounts of elastin exist throughout the disc tis-sues78"1820. Although the non-collagenous proteins havenot been extensively studied, they appear to contributesignificantly to the organization and stability of thematrix20. The contribution of elastin to the mechanicalproperties of the disc remains uncertain, but its lowconcentration suggests that it does not have a majorrole.

BLOOD SUPPLY AND INNERVATIONNormal discs in skeletally mature individuals have a

limited vascular supply and limited innervation7. Bloodvessels lie on the surface of the annulus and may pen-etrate a short distance into the outer layers. The bloodvessels of the vertebral bodies lie directly against theendplates but do not enter the central regions of thedisc. Simple and plexiform unmyelinated nerve endingsand encapsulated nerve endings have been found onthe surface of the annulus and small nerves with simplefree nerve endings enter the outer layers of the annu-lus, but nerves have not been identified within the cen-tral regions of normal discs. Facet joint capsules andspinal ligaments have free and encapsulated nerve end-ings.

FUNCIIONThe unique structure and composition of the inter-

vertebral disc make possible its specialized mechanicalfunctions32: maintaining the alignment and stability ofthe spine, allowing movement between vertebrae andabsorbing and distributing loads applied to the spine.Collagen fibers of the annulus pass into the bone of thevertebral bodies binding adjacent vertebrae together,contributing to the stability of the spine and joining theannulus to the vertebral bodies. They also contain thenucleus pulposus between the vertebral endplates andthe annulus (Figure 2). The dense collagenous circum-ferential lamellae of the outer annulus fibrosus resistlarge tensile stresses, minimizing intervertebral discbulging and annulus fibrosus strains during compres-sion, bending and torsional loading of the disc (Figure4). The less dense collagenous matrix of the inner an-nulus may permit larger deformations in response toloadings, and these larger deformations create fluidflows that dissipate energy. The high water andproteoglycan content of the normal nucleus pulposusenables it to function predominantly as a viscous fluidunder static loading conditions. The swelling pressure

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Figure 4. Schematic diagram showing the mechanical function of the intervertebral disc. Under minimal axial load, the high water andproteoglycan content of the nucleus pulposus maintain the height of the disc (left). Axial loading and compression force fluid from the discand decrease disc height (middle). After cessation of axial loading, flow of fluid into the disc restores its height (left). Bending of the spine,flexion, and extension cause eccentric deformation of the disc (right).

resulting from the high proteoglycan concentrationhelps maintain disc height and contributes to load sup-

port and load distribution. The flow of water in and outof the disc across the cartilage endplates helps transferloads in a uniform manner across the inner annulusfibrosus and nucleus pulposus. Fluid flow is also respon-sible for the loss of disc height during prolonged com-

pression loading and for the ability of discs to regaintheir original height after cessation of prolonged load-ing (Figure 4). Thus, the specialized component tissuesof intervertebral disc form a structure that providesspine stability while allowing motion and absorbing anddistributing loads. The outer annulus fibrosus resiststensile loads and contains the inner annulus fibrosusand nucleus pulposus limiting their deformations; theinner annulus fibrosus and nucleus pulposus contrib-ute to the viscoelastic behavior of the disc, includingmaintaining or restoring disc height and absorbing loadsapplied to the spine.

DEVELOPMENT AND AGINGDisc volume and shape change with skeletal devel-

opment and growth and then again following skeletalmaturity6'7. Following birth, the disc rapidly grows inheight and diameter to keep pace with the growth ofthe vertebral column. The changes in volume and shapethat occur following skeletal maturity vary among indi-viduals and among discs. Unfortunately, they have notbeen well defined or correlated with the changes in tis-sue structure and composition. However, the primaryalterations in disc volume and shape that occur withaging include a loss of disc height, or protrusion of thecentral disc into the vertebral body with a decrease in

the height of the annulus, and buckling or bulging ofthe annulus.

Changes in disc tissue structure and composition pre-cede and accompany the alterations in gross morphol-ogy. The changes in disc size, vascular supply and com-

position, especially proteoglycan organization andproteoglycan and water concentration, begin duringgrowth and development. These changes occur wellbefore evidence of disc degeneration appears, but theymay form the basis for the changes that occur follow-ing skeletal maturity including degeneration9' 15. In thissense the age related changes of the disc begin soon

after birth. Although all the disc tissue components andthe endplates change from birth through old age7 25, themost extensive changes occur in the nucleus pulposuswhere the number of viable cells and the concentrationsof proteoglycans and water all decline. This is accom-

panied by fragmentation of the aggregatingproteoglycans and increases in the concentrations ofcollagens and non-collagenous proteins7" 2-14' 8. All discseventually develop similar age-related changes, butwithin the same individual and among individuals theyvary in rate and extent. Thus, specific discs may changemore rapidly or more slowly than the time sequencedescribed in the following sections.

NEWBORNAt birth, distinct hyaline cartilage endplates separate

the disc tissues from the vertebral bodies. The outerrim of the annulus consists of dense circumferentiallayers of collagen fibrils that penetrate the cartilageplates of the vertebrae. Occasional elastic fibers lie par-allel to the collagen fibrils. Small blood vessels may be


J. A. Buckwalter

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found between the lamellae of the outer annulusfibrosus, especially in the posterolateral regions of thedisc and in and adjacent to the cartilage plates. Occa-sional blood vessels penetrate the inner annulus. Nu-merous perivascular and free nerve endings lie on andamong the most peripheral layers of the annulus. Thenucleus fills almost half the disc and consists primarilyof notochordal tissue: a soft gelatinous, clear matrixsurrounding syncytial cords and clusters of notochordalcells (Figure 3, Top). The matrix of the nucleus con-tains few collagen fibrils and even more rare sheets ofelastin embedded in an abundant network of highlyhydrated proteoglycans. Throughout the newborn disctissues, collagen fibrils have a nearly uniform small di-ameter. Proteoglycan aggregates from newborn andinfant intervertebral disc annulus fibrosus and cartilageend plate have the same structure as aggregates fromhyaline cartilages'2",4" 5. However, only about one-thirdof nucleus pulposus proteoglycan aggregates resemblethese large aggregates. The other two-thirds consist ofaggrecan clusters that frequently lack a visible centralhyaluronan filament.

CHILDHOOD AND ADOLESCENCEDuring skeletal growth, disc volume increases many

fold, thereby increasing the distance between the cen-tral regions of the disc and the peripheral blood ves-sels. At the same time, the blood vessels of the annulusand the vertebral cartilage endplate become smaller andless numerous. The fibrocartilagenous component of theannulus increases in size, but in early adolescence thenucleus pulposus still comprises nearly half the disc andcan easily be distinguished from the fibrocartilage ofthe inner annulus. During this time the number of no-tochordal cells decreases and chondrocyte like cellsappear in the central regions of the disc (Figure 3).More collagen fibrils appear in the nucleus and the col-lagen fibrils of all disc components increase in meandiameter and variability in diameter. The proportion ofproteoglycans that form aggregates and proteoglycanaggrecan size both decrease, and large proteoglycanaggregates similar to those found in articular cartilagedisappear6" 2-1525. By adolescence, the proteoglycan popu-lation of the nucleus pulposus consists almost entirelyof clusters of short aggrecan molecules and non-aggre-gated proteoglycans. A decline in the concentration offunctional link protein may cause at least some of thechange in proteoglycan aggregates'2-'525.

ADULTWith skeletal maturity, many of the remaining pe-

ripheral blood vessels disappear. The outer annulusfibrosus stays about the same relative size, but the ap-

parent size of the fibrocartilagenous inner annulus ex-pands at the expense of the nucleus, as the nucleus be-comes progressively more fibrotic. In portions of theannulus, myxomatous degeneration develops with lossof the normal collagen fibril organization. Fissures andcracks appear in the disc and may extend from the pe-riphery to the central regions. The nucleus becomesfirm and white rather than soft and translucent. In allregions of the disc inside the outer annulus, the con-centration of viable cells declines sharply, especially inthe most central regions7'28'29. Few if any notochordalcells remain, but the central regions of the nucleus con-tain scattered viable chondrocyte like cells.Proteoglycan and water concentrations30 decrease andcollagen and non-collagenous protein concentrationsincrease"7 as dense granular material accumulatesthroughout the matrix (Figure 3, Middle and Bot-tom)7"1'28'29. Although this material accumulates through-out the matrix, it appears to concentrate in the regionsimmediately surrounding the cells, and forms thicksheaths around some collagen fibrils7"1'. Its compositionremains unknown, but it may contain degraded matrixmolecules or noncollagenous matrix proteins includingfibronectin.

ELDERLYLate in adult life the entire disc inside the outer lamel-

lae of the annulus becomes a plate of fibrocartilage thattypically contains fissures and areas of myxoid tissue.It may be difficult if not impossible to distinguish theinner annulus from the nucleus pulposus by gross ex-amination, although the region of the nucleus may stillhave smaller diameter, less densely packed collagenfibrils. In the central regions of the disc, few viable cellsremain (Figure 5). The height of the disc may declinefurther and prominent fissures and clefts may form inthe center.

DEGENERATIONAll discs age, but not all discs degenerate. Disc de-

generation is the age related deterioration of disc struc-ture and alteration of disc composition that leads to lossof disc mechanical function including loss of the abilityto maintain disc height, allow normal spine motion andabsorb and distribute loads. Discs that have almost dis-appeared, leaving only a thin layer of fibrotic tissue sepa-rating adjacent vertebral bodies, represent the end stageof the degenerative process (Figure 6). Some individu-als develop advanced disc degeneration in mid life whileothers in their ninth decade have little detectable lossof disc structure and function. In addition, one disc mayundergo rapid severe degeneration while the others inthe same individual appear normal. The reasons for

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Figure 6. Radiographs showing advanced degeneration of an inter-vertebral disc. Notice the almost complete loss of disc height andthe formation of vertebral osteophytes. Top: anterior-posterior ra-diograph. Bottom: lateral radiograph.

Figure 5. Electron micrograph showing the remains of a necroticnucleus pulposus cell. V indicates membrane bound vacuoles andthe arrows mark dense cell debris.

these differences among and within individuals remainpoorly understood, although some of the differencesamong individuals may be genetically determined4.

In many instances, advanced disc degeneration isassociated with vertebral body osteophytes, increasedbone density or sclerosis of the vertebral bodies adja-cent to the disc, and facet joint osteoarthritis (Figures6 and 7). Small blood vessels proliferate in the endplatesand vertebral bodies and grow into the peripheral re-gions of degenerated discs5'23. Extension of nerves intothe inner regions of the disc may accompany this vas-cular proliferation and vascular ingrowth, and severalauthors have found evidence that these changes areassociated with back pain5'19'27. The loss of disc tissueresults from the action of degradative enzymes withinthe disc and the inability of disc cells to maintain orrestore their matrix. This last stage of disc degenera-tion leads to a loss of spinal mobility and abnormal load-ing of the facet joints, spinal ligaments and muscles.

The osteophytes that develop in association with ad-vanced disc degeneration may lead to compression ofnerve roots and spinal stenosis (Figure 7)1.

Although the end stage of intervertebral disc degen-eration can be identified by imaging studies and grossexamination (Figures 4 and 5), generally accepted cri-teria for the diagnosis of disc degeneration and for dis-tinguishing between disc aging and degeneration havenot been established. Correlation of changes in disc size,shape, composition and mechanical properties with al-terations in spine function should make it possible todevelop these criteria25. These types of studies mayeventually show that disc degeneration differs from thenormal aging of the disc much like osteoarthritis ordegenerative joint disease differs from normal aging ofsynovial joints. In both synovial joints and the jointsformed by vertebral bodies and intervertebral discs,degenerative changes may or may not be associatedwith pain. Articular cartilages and intervertebral discschange with age, and degeneration of both these tis-sues is closely correlated with increasing age"5. How-ever, despite aging changes, these tissues continue tofunction well throughout life in many individuals. Thus,



Figure 7. Drawing showing degenerative changes ofthe spine. Noticethe advanced degeneration of the L4-L5 and L5-S1 intervertebraldiscs, the formation of vertebral and facet joint osteophytes andthe narrowing of the intervertebral foramina by the osteophytes(adapted from a drawing by F. Netter published in Buckwalter,J.A., Martin, J. Degenerative joint disease. In Clinical Symposia.47 (2), Ciba-Geigy, 1995).

disc degeneration may result from either an accelera-tion or exacerbation of normal aging, or it may be adistinct process that is superimposed on normal aging.At present, it is not possible to distinguish betweenthese alternatives.

MECHANISMS OF INTERVERTEBRALDISC DEGENERATION

A variety of mechanisms may contribute to disc de-generation including declining nutrition, decreasingconcentration of viable cells, cell senescence, loss ofaggregating proteoglycans, modification of matrix pro-teins, degradative enzyme activity, accumulation of de-graded matrix macromolecules and fatigue failure of thematrix6"5. Although each of these mechanisms may al-ter disc composition and structure, their relative impor-tance and the interactions among them have not beenestablished'5.The most critical event responsible for the changes

in central disc cells and their matrices appears to bedeclining nutrition6"8'31. The disc cells rely on diffusionof nutrients through the matrix from blood vessels on

the periphery of the annulus fibrosus and within thevertebral bodies. The increase in disc volume duringgrowth combined with the progressive age related de-cline in the number of arteries supplying the peripheryof the disc, and possibly calcification of the cartilageendplates, impair delivery of nutrients and removal ofwastes18"3. At the same time the blood supply to theperiphery of the disc declines, accumulation of degradedmatrix macromolecules and decreasing matrix waterconcentration within the central disc may interfere withdiffusion through the matrix, further compromising cellnutrition. Not only does the supply of nutrients decline,rising lactate concentration, due to increased lactate pro-duction as a result of low oxygen tension and decreasedrate of lactate removal, decreases the pH. Declining pHcompromises cell metabolism and biosynthetic func-tions, and can cause cell death. Factors that may in-crease the rate and severity of age-related changes inintervertebral discs by indirectly altering nutrition in-clude increased disc loading due to demanding physi-cal activities, immobilization, vibration and spinal defor-mity1. Factors that directly compromise the vascularsupply include smoking, vascular disease and diabetes1.The age related decline in nutrition of the central

disc region and the accompanying decline in pH wouldbe expected to adversely affect cell viability, and elec-tron microscopic studies show that the proportion ofnecrotic cells increases with age (Figure 5)7,28,29. In fe-tal and infant intervertebral discs, no more than 2% ofthe nucleus pulposus cells showed morphologic signsof necrosis. In some adolescents and young adult discs,more than 50 percent of the nucleus cells were necrotic,and in samples from elderly people more than 80 per-cent of the cells were necrotic.

Although changes in disc cell function with age havenot been extensively studied, in other tissues decliningcell function contributes to age-related tissue degenera-tion'5. Even without an alteration in cell nutrition, manynormal differentiated cells become senescent with in-creasing age. They remain viable, but they lose theircapacity to replicate DNA, part or all of their syntheticcapacity and some other specialized functions. Experi-mental evidence suggests that these alterations resultfrom changes in gene expression, and that transcrip-tion factors, proteins that bind to specific sequences ofDNA and direct gene expression, control these age-re-lated changes.

Mature intervertebral discs lack large proteoglycanaggregates and aggrecans similar to those found in ar-ticular cartilage6'12-14. A population of articular cartilagelike proteoglycan aggregates exists in the discs of new-borns, but these aggregates disappear during matura-tion, and the aggrecans become shorter'2 3. Other work

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shows that a decline in proteoglycan concentration pre-cedes and accompanies disc degeneration25. The lossof proteoglycan aggregates and large aggrecans and de-creased proteoglycan concentration decrease the abil-ity of the disc to maintain a high water concentration,thereby increasing the loading of the collagenous com-ponent of the matrix. These changes combined with theincreasing collagen concentration and accumulation ofnon-collagenous proteins, including fibronectin and oth-ers, make the central disc fibrotic and stiff, and decreaseits ability to maintain disc height and to distribute loads.

With increasing age, connective tissue matrices, in-cluding those of intervertebral disc tissues, tend to losetensile strength'532. Some of this loss may result frommodifications of the collagens'5'24 that include increasedor altered cross-linking, impaired fibril formation anddenaturation2212433. Increasing collagen cross linksthrough non-enzymatic glycation or lipid peroxidationmay cause increasing brown pigmentation with age, and,more importantly, alter disc mechanical properties. Inaddition to their potential effects on tissue mechanicalproperties, glycation products also can stimulate cells,including chondrocytes, to release cytokines and pro-teases that contribute to tissue degeneration24. Exami-nation of adult human intervertebral discs has showngreater denaturation of type-II collagen (loss of triplehelical configuration) in the annulus fibrosus andnucleus pulposus than in articular cartilage from thesame individuals21. This difference may result from ac-cumulation of degraded molecules in the intervertebraldisc and could alter the mechanical properties of thecollagen fibril framework and the interaction of type-IIcollagen fibrils with other matrix molecules.

Throughout life, disc cells synthesize matrix mol-ecules to replace older molecules that are enzymaticallydegraded in the matrix. A balance between synthesisand degradation maintains the tissue. Thus, the loss ofdisc tissue seen in advanced disc degeneration (Figures6 and 7) must result from excessive degradation rela-tive to synthesis, but the cause of this imbalance be-tween synthetic and degredative activity in degenerat-ing discs remains unknown.

With aging, accumulation of partially degraded mol-ecules may alter the properties of the disc, includingthe mechanical behavior of the tissue and the ability ofnutrients and metabolites to diffuse through the ma-trix. Increasing concentrations of degraded molecules,and possibly non-collagenous proteins, may inhibit orinterfere with the ability of cells to synthesize newmolecules. Accumulation of degraded molecules mayalso interfere with assembly of newly synthesized mol-ecules in the matrix. For example, accumulation ofhyaluronan binding fragments of proteoglycan aggrecan

core proteins may interfere with assembly ofproteoglycan aggregates'3"526. Accumulation of de-graded matrix molecules is most likely to occur in tis-sues that lack a blood supply and have relatively slowdiffusion of molecules through their matrix, like thecentral regions of the intervertebral disc.

Normal spine movement and absorption of loads re-quires loading and deformation of discs followed byrecovery of disc shape (Figure 4). In addition, main-taining an upright posture decreases disc height bydriving water out of the disc matrix. Prolonged recum-bency then restores the original disc shape and volumeas water returns to the matrix. These repetitive defor-mations of the disc may lead to fatigue failure of thematrix. This failure may appear as fissures, cracks ormyxoid degeneration, or as more subtle changes in themacromolecular framework of the matrix including frag-mentation of proteoglycans and disruption of collagenfibrils and the relationships between collagen fibrils andother matrix macromolecules. These alterations of thematrix may expose cells to increased loads that com-promise their function.Age related changes in the disc may make the tis-

sue less able to recover from deformation and morevulnerable to progressive fatigue failure of the matrix.Loss of proteoglycans and water from the central discregions increases loading of the collagen network.Modifications of the collagens, decreased water concen-tration and accumulation of degraded matrix moleculesmay make the collagen framework more vulnerable tofailure, and the decline in cell nutrition, decreased con-centration of viable cells and cell senescence combinedwith the alterations in the matrix may compromise theability of the cells to repair damage to the matrix mac-romolecules.

INTERVERTEBRAL DISCDEGENERATION AND PAIN

The relationships between disc degeneration andpain remain poorly understood. Some individuals withminimal morphologic evidence of disc degenerationhave chronic back pain and stiffness, while others withadvanced disc degeneration have minimal symptoms.The available information suggests that intervertebraldisc degeneration may contribute to back pain throughthree possible mechanisms: loss of disc structure andmechanical properties, release of mediators that maysensitize nerve endings and nerve and blood vessel in-growth into degenerated discs. The loss of disc struc-ture and mechanical properties alters loading and align-ment of vertebral bodies, facet joints, spinal ligamentsand muscles, and decreases the ability of the discs toabsorb and distribute loads applied to the spine. These


Do Intervertebral Discs Deserve 7heir Bad Reputation?

changes may increase stimulation of nerve endings inbone, spinal ligaments, facet joint capsules and muscles.By altering the mechanical function of the spine andthe alignment of the facet joints, long standing advanceddisc degeneration may initiate or accelerate develop-ment of osteoarthritis of the facet joints (Figure 7)16. Inaddition to these structural and mechanical changes,the cell and matrix changes associated with disc degen-eration, including cell necrosis, may be associated withrelease of cytokines, free radicals, matrix degradationproducts and other molecules. Some of these substancesmay sensitize nociceptive nerve endings and therebycontribute to the development of back pain. Althoughnormal intevertebral discs rarely have nerve fibers orblood vessels that penetrate further than the outer an-nulus, nerves and blood vessels have been identified inthe inner annulus and even in the nucleus pulposus ofdegenerated discs, and these changes have been cor-related with back pain1927.

CONCLUSIONSDo intervertebral discs deserve their bad reputation?

To at least some degree, yes. At the time of skeletalmaturity, intervertebral discs are impressive structures.They are well designed to stabilize the spine, maintainthe alignment of the vertebral bodies and facet joints,allow movement between vertebral bodies and distrib-ute loads. However, they are not well designed to last alifetime. After middle age, or sooner, alterations of theirstructure and composition decrease their ability to al-low movement between vertebral bodies and absorbloads. Some discs degenerate; that is, much or most ofthe disc tissue is lost reducing disc volume and height,altering the alignment and loading of the facet jointsand stiffening and shortening the spine. Disc degen-eration may also lead to mechanical failure of the annu-lus, osteophyte formation, blood vessel proliferation inthe region of the endplates and penetration of the innerdisc tissues by blood vessels and nerves. In its mostsevere form, disc degeneration leaves only a thin plateof fibrous tissue separating adjacent vertebral bodies.While the adverse effects of advanced disc degenera-tion on spine mechanical function are apparent, the re-lationships between disc degeneration and pain are lessclear. Some individuals with almost complete loss of oneor more intervertebral discs have little or no discom-fort while others have intermittent or chronic pain. Thereasons for this variability remain unknown, but discdegeneration may cause pain by contributing to thedevelopment of facet joint osteoarthritis, nerve rootcompression and spinal stenosis, release of mediatorsthat sensitize nociceptive nerve endings and by stimu-lating proliferation and ingrowth of blood vessels and

nerve fibers. If intervertebral discs deserve their repu-tation for causing back stiffness and pain, it is reason-able to consider why an important structure begins todeteriorate soon after skeletal maturity. Intervertebraldiscs represent perhaps the best example of how natu-ral selection guided the evolution of structures or or-gans that function well until, or somewhat past, the ageof peak reproductive fitness, but then deteriorate, andin some instances almost disappear, within a decade.Unfortunately, genes that could lead to formation ofintervertebral discs that maintain their composition,structure and function for eight decades or more wouldnot have given their possessors much advantage in pass-ing on those genes.

REFERENCES1. Andersson, G.BJ.: Intervertebral disk: Clinical as-

pects. In Musculoskeletal Soft Tissue Aging: Impacton Mobility, pp. 331-347. Edited by J.A. Buckwalter,V.M. Goldberg and SL-Y Woo. Rosemont, IL, Ameri-can Academy of Orthopaedic Surgeons, 1993.

2. Antoniou, J.; Steffen, T.; Nelson, F.;Winterbottom, N.; Holiander, A.P.; Poole, R.A.;Aebi, M.; and Alini, M.: The human intervertebraldisc: Evidence for changes in the biosynthesis anddenaturation ofthe extracellular matrix with growth,aging and degeneration. J. Clin. Invest., 98(4):996-1003, 1996.

3. Ayad, S., and Sandell, LJ.: Collagens of the inter-vertebral disk: Structure, function, and changes dur-ing aging and disease. In NewApproaches to Low BackPain, pp. 539-556. Edited by J.W. Weinstein and S.L.Gordon. Rosemont, IL, American Academy of Ortho-paedic Surgeons, 1996.

4. Battie, M.C., and Kaprio, J.: The role of geneticinfluences in disk degeneration and herniation. InNew Approaches to Low Back Pain, pp. 85-96. Editedby J.W. Weinstein and S.L. Gordon. Rosemont, IL,American Academy of Orthopaedic Surgeons, 1996.

5. Brown, M.F.; Hukkanen, M.V.; McCarthy, I.D.;Redfern, D.R.; Batten, JJ.; Crock, H.V.; Hughes,S.P.; and Polak, J.M.: Sensory and sympathetic in-nervation of the vertebral endplate in patients withdegenerative disc disease. J. Bone and Joint Surg.,79B:147-153, 1997.

6. Buckwalter, J.A.: Aging and degeneration of thehuman intervertebral disc. Spine, 20:1307-1314,1995.

7. Buckwalter, J.A.: Fine structural studies of the hu-man intervertebral disc. In Idiopathic Low Back Pain,pp. 108-143. Edited by A.A. White and S.L. Gordon.St. Louis, Mosby, 1982.

8. Buckwalter, J.A; Cooper, R.R.; and Maynard,J.A.: Elastic fibers in human intervertebral discs.J. Bone and Joint Surg., 58A:73-76, 1976.

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9. Buckwalter, J.A., and Martin, J.A.: Intervertebraldisc degeneration and back pain. In New Approachesto Low Back Pain, pp. 607-623. Edited by J.W.Weinstein and S.L. Gordon. Rosemont, IL, AmericanAcademy of Orthopaedic Surgeons, 1996.

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Volume 18 11

do intervertebral discs deserve their bad reputation?

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