Michael A. Adams, PhD; Brian J. C. Freeman, FRCS; Helen P. Morrison,
MBChB; Ian W. Nelson, FRCS; Patricia Dolan, PhD
From the *University of Bristol, the ~Queens Medical Centre, Nottingham,
and the ±Frenchay Hospital, Bristol, United Kingdom.
Study Design. Mechanical testing of cadaveric lumbar motion
Objectives. To test the hypothesis that minor damage to
a vertebral body can lead to progressive disruption of the adjacent
Summary of Background Data. Disc degeneration involves gross
structural disruption as well as cell-mediated changes in matrix
composition, but there is little evidence concerning which comes
first. Comparatively minor damage to a vertebral body is known to
decompress the adjacent discs, and this may adversely affect both
structure and cell function in the disc.
Methods. In this study, 38 cadaveric lumbar motion segments
(mean age, 51 years) were subjected to complex mechanical loading
to simulate typical activities in vivo while the distribution of
compressive stress in the disc matrix was measured using a pressure
transducer mounted in a needle 1.3 mm in diameter. "Stress profiles"
were repeated after a controlled compressive overload injury had
reduced motion segment height by approximately 1%. Moderate repetitive
loading, appropriate for the simulation of light manual labor, then
was applied to the damaged specimens for approximately 4 hours,
and stress profilometry was repeated a third time. Discs then were
sectioned and photographed.
Results. Endplate damage reduced pressure in the adjacent
nucleus pulposus by 25% ± 27% and generated peaks of compressive
stress in the anulus, usually posteriorly to the nucleus. Discs
50 to 70 years of age were affected the most. Repetitive loading
further decompressed the nucleus and intensified stress concentrations
in the anulus, especially in simulated lordotic postures. Sagittal
plane sections of 15 of the discs showed an inwardly collapsing
anulus in 9 discs, extreme outward bulging of the anulus in 11 discs,
and complete radial fissures in 2 discs, 1 of which allowed posterior
migration of nucleus pulposus. Comparisons with the results from
tissue culture experiments indicated that the observed changes in
matrix compressive stress would inhibit disc cell metabolism throughout
the disc, and could lead to progressive deterioration of the matrix.
Conclusions. Minor damage to a vertebral body endplate leads
to progressive structural changes in the adjacent intervertebral
Recent pain provocation studies have confirmed that severe and
chronic back pain can be produced by mechanical stimulation of degenerated
intervertebral discs (50,59,74). Magnetic resonance imaging (MRI)
and discographic studies, However, show poor correspondence between
generalized disc degeneration and back pain, suggesting that only
certain features of degenerated discs are likely to be painful,
such as a radial fissure in the anulus fibrosus (60) or posterior
disc protrusion (18). Other "degenerative" changes such as loss
of signal intensity from the nucleus may be only signs of aging
(83). Also, degenerative changes may become less painful as they
become more severe because disc narrowing can cause the disc to
be protected from mechanical loading by the adjacent apophyseal
joints (12,31). Despite these complications, there is no doubt that
disc degeneration can be painful, yet surprisingly little is known
Even defining disc degeneration is difficult. Degeneration involves
biological (cell-mediated) changes, which are most pronounced in
the nucleus (8,26,66,81) and gross structural changes, which are
most evident in the anulus and endplate (5,26,41,81). Common structural
changes include radial fissures, circumferential clefts and rim
tears in the anulus (81), inward buckling of the inner anulus, reduced
disc height, endplate defects, and vertical bulging of the endplates
into the adjacent vertebral bodies.
A less common but clinically important structural change is herniation
of nucleus pulposus through the anulus or endplate. Changes in the
discs often are accompanied by arthritic changes in the apophyseal
joints, and by osteophytes around the margins of the vertebral bodies
(81). Disc function deteriorates along with its structure: A healthy
disc contains a soft and highly hydrated central region, the nucleus
pulposus, which acts as a hydraulic cushion to distribute stress
evenly between vertebrae, whereas degenerated discs have only a
small hydrostatic region, or none, and exhibit high stress concentrations
in the anulus (5,12).
Traditionally, disc degeneration has been linked to mechanical
loading, although direct post mortem confirmation of this is relatively
recent (85). Gross structural disruption certainly appears to represent
mechanical failure, but tissue composition often is changed as well,
and it is not clear whether discs fail mechanically because they
are weakened by biochemical changes, or whether the latter represent
a cellular response to mechanical failure. The importance of mechanical
factors in disc degeneration is emphasized by experiments on cadaver
spines, which show that disc prolapse and radial fissures can be
simulated in apparently normal discs if the loading is sufficiently
severe (7,57) or relentless (6,32,76) and by animal experiments
showing that biological degeneration always occurs after scalpel-induced
structural failure (69,72).
The issue is far from settled, however, because epidemiological
studies on identical twins suggest that inheritance is the largest
single determinant of disc degeneration (16), and this inheritance
is at least partly genetic in nature (84). There may be genetic
weaknesses in the collagen framework of the disc or genetic influences
on blood supply and disc metabolism (84). Equally, genetic susceptibility
may involve mechanical factors such as small discs, a heavy torso,
or small internal levers, which would lead to high internal muscle
force acting on the disc.
The problem of whether disc degeneration usually is initiated by
mechanical or biological factors is important because it affects
strategies of research on the prevention and cause of disc-related
back pain. Currently, there is considerable interest in identifying
biochemical and metabolic abnormalities in degenerated disc tissues
(27,35,45,46,66), but these abnormalities may be consequences of
disc failure rather than causes, and the precise sequence of biologic
events after some mechanical disruption may offer little opportunity
for intervention. Similarly, efforts to measure and regulate spinal
loading (29) may be of little use in preventing back pain if primary
biochemical factors can predispose discs to fail under low loads.
Cause and effect is difficult to establish because any biochemical
weakening would lead directly to mechanical disruption, and mechanical
disruption would influence disc cell metabolism immediately through
its effect on matrix compressive stress (13,38,42).
One way of tackling this problem of cause and effect is to uncouple
the close links between mechanical factors and study one factor
in isolation. Experiments on cadaver spines performed over a few
hours enable cell-mediated events to be ignored so mechanical factors
that might initiate disc degeneration can be studied in detail.
If cadaver experiments could show that physiologically reasonable
mechanical loading can consistently create all of the commonly observed
structural changes that typify disc degeneration, this would add
weight to the "mechanics first" argument. The argument would be
strengthened further if the mechanically induced structural changes
could be shown to alter the matrix compressive stresses in a manner
that would be expected to inhibit disc cell metabolism.
Previous cadaver experiments have demonstrated that disc herniation
(7,57), radial fissures (6,32) and posterior disc bulging (4,7),
can be caused by severe or repetitive mechanical loading of apparently
normal discs, but several problems remain. No explanation exists
for the types of internal disruption that occur in the lamellar
structure of the anulus (28,36,77,80), which are more common than
disc prolapse. Also, it is difficult to explain how mechanical loading
could cause disc degeneration in sedentary people who recall no
preceding injury. A possible solution to both problems was suggested
by a recent study from the laboratory of the current authors (13),
which showed that even slight mechanical damage to the weakest link
of the lumbar spine, the vertebral body end plate, affected stress
distributions in the adjacent disc in a manner that could lead to
internal disruption of the disc. Fatigue damage to the endplates
can occur at loads well within the normal range of spinal loading
in life (19,39).
The purpose of the current study was to extend the previous experiment
of the authors and test the hypothesis that minor damage to a vertebral
body can lead to progressive disruption of the adjacent disc.
Materials and methods.
Overview of experiments.
In this study, 38 cadaveric lumbar "motion segments" were used
in three experiments. The first experiment compared the severity
of endplate damage with changes in the distribution of compressive
stress in the adjacent disc. It also sought to identify which discs
were affected the most by end plate damage. The second experiment
investigated how affected discs would respond to subsequent cyclic
loading: Would it cause a redistribution of fluid in the disc and
a consequent equalization of stress, or would it intensify the stress
concentrations caused by the endplate damage? The third experiment
examined the ability of the discs to equalize compressive stress
in flexed and lordotic "postures," both before and after endplate
After testing, the discs were sectioned and photographed so structural
changes caused by mechanical loading could be compared with those
that typify degenerated discs. Changes in the distribution of matrix
compressive stress were interpreted in the light of recent experiments
on disc tissue metabolism to infer the likely response of disc cells
to the structural defects created by mechanical loading.
Cadaveric lumbar spines were obtained from individuals whose cause
of death was unrelated to spinal pathology. These were stored in
sealed plastic bags at -20 C for up to 6 months. The spines were
radiographed to exclude any that exhibited such advanced disc degeneration
(including gross narrowing and bridging osteophytes) that dissection
and testing would have been difficult.
In the experiments, 19 spines, 19 to 87 years of age, were used.
When needed for testing, each spine was defrosted at 3 C in its
sealed bag and then dissected into two "motion segments" consisting
of two complete lumbar vertebrae and the intervening disc and ligaments.
One motion segment was tested immediately. The other was resealed
in a bag, stored at 3 C, and tested the next day. The following
levels were represented: L5/S1 (2 motion segments), L4/L5 (13 motion
segments), L3/L4 (4 motion segments), L2/L3 (12 motion segments),
L1/L2 (4 motion segments), and T12/L1 (3 motion segments). Of these
motion segments, 30 were male and 8 were female. The mean age of
the motion segments was 51 +/- 16 years.
Each motion segment was secured in two cups of mildly exothermic
dental plaster and tested on a computer-controlled hydraulic materials
testing machines (Dartec, Stourbridge, UK). Complex loading in bending
and compression was applied by means of two low-friction rollers.
When the rollers were of equal height, the specimen was subjected
to pure compression. When the rear roller was lower, the specimen
was loaded initially in bending by the front roller, and thus flexed
forward until the rear roller made contact with the load-cell plate.
The specimen was then loaded in compression and bending. The apparatus
did not impose ant axis of flexion-extension, but allowed small
"settling" movements in the horizontal plane while complex loading
was applied at physiological loading rates. Throughout the testing
period, the disc was surrounded in cling-film to keep its surface
moist. In this way, the swelling pressure of the disc was able to
oppose the load-induced outflow of the fluid.
Preliminary creep test.
Each motion segment was subjected to a pure compressive force of
300 Newton's for approximately 15 minutes as a precaution against
any postmortem superhydration effects. This force was sufficient
to cause an approximate 0.1 to 0.2-mm loss in disc height, with
the result that the disc approached (but did not reach) equilibrium
with the 300 N. In life, the lumbar spine is subjected to approximately
200 N during each night's rest, and 500 N during relaxed standing
Measurement of intradiscal compressive stress.
A static compressive load of 2 kN, sufficient, to simulate light
manual labor (63), was applied to the motion segment for a period
of 20 seconds. During this time, the distribution of compressive
stress in the disc was measured at a frequency of 25 Hz by pulling
a miniature pressure transducer through it, alone its sagittal midline.
The transducer was a small strain-gauged membrane mounted in the
side of a needle 1.3 mm in diameter (58). The anulus has excellent
self-sealing properties (6,52), so no disc material was expressed
through the needle hole during the experiments. Validation tests
have shown that the output of the transducer in disc tissues is
approximately equal to the average compressive acting perpendicularly
to the membrane (55). Rotating the needle about its long axis enabled
the vertical and horizontal components of compressive stress to
be measured in successive tests using the same needle track.
Each pair of "stress profiles" was analyzed as described previously
(12) for the purpose of calculating the following: the width of
the hydrostatic nucleus (expressed as a percentage of the anteroposterior
diameter of the disc), the average pressure in the nucleus, and
the peak stress (horizontal or vertical) in the anterior anulus
and the posterior anulus regions of the profiles. Peak vertical
stresses usually were greater than peak horizontal stresses (12).
The hydrostatic nucleus was defined as the region of the profile
in which the vertical and horizontal stresses did not differ from
each other or vary with location by more than 5%.
Damage to the vertebral endplate.
After the initial stress profilometry, each motion segment was
position in the moderate flexion to simulate the flat back adopted
when ordinary people lift weights from the ground (29,30). Flexion
angles reflected the mobility of each motion segment, and thus ranged
from 4 degrees for elderly upper-lumbar motion segments to 8 degrees
for young lower lumbar motion segments. A compressive overload injury
then was simulated as follows: The ram of the Dartec moved upwards
at approximately 2.5 mm/second until the first signs of damage were
evidenced by a slight reduction in gradient of the force deformation
graph, which was plotted in real time (13). The load was then removed
immediately. Damage was confirmed by compressing the specimen a
second time and noting the residual displacement from the force-displacement
graphs. The damage was quantified by measuring residual displacement
at a compressive force of 1 kN. Because this measure shows the permanent
loss of motion segment height resulting from the mechanical overload,
it is a better measure of damage than that used previously in the
authors' laboratory (13). Compressive damage occurs in the vertebral
body endplate rather than the disc (19,20,25,71) and might occur
in life during a fall on the buttocks, or by the process of fatigue
failure during repetitive strenuous lifting. Endplate damage sustained
by sudden compressive overload in vitro is similar to that resulting
from cyclic loading (19,20), but is more convenient to reproduce
in the laboratory. Approximately 5 minutes elapsed between the last
stress profile measured before endplate damage and the first measured
after the damage.
All 38 specimens were used. After the preliminary 15-minute creep
test, stress profiles were obtained with the motion segment positioned
in the neutral position (0 degrees), which involves neither flexion
nor extension. Next, the endplate was damaged as described earlier
and stress profilometry repeated. Changes in the stress profiles
were compared with the following specimen characteristics: age,
lumbar level, and height loss (i.e., severity of damage).
After the endplate had been damaged, 19 of the specimens used in
Experiment 1 were subjected to cyclic compressive loading. The last
to be tested, these 19 specimens were not selected in any other
way. Nine motion segments were position in moderate flexion (4-8
degrees) to simulate a "flat back," and 10 motion segments were
positioned at 2 degrees of extension to simulate lordotic standing
postures (4). Between 8000 and 10,000 linear, 1.5 to 3 kN (mean,
2.2kN), depending on specimen size and age. This is appropriate
to the simulation of moderately light manual labor (63). Stress
profilometry was repeated a third time immediately after cyclic
The influence of "posture" on the 19 motion segments in experiment
2 was examined by repeating the stress profilometry in 2 degrees
of extension and 4 to 8 degrees of flexion. Stress profiles were
obtained in these two postures and the neutral posture (0 degrees)
before and after endplate damage, then again after cyclic loading.
Examination of disc structural damage.
Immediately after testing, 15 of the 19 specimens in Experiments
2 and 3 were frozen at -80 degrees and subsequently sectioned in
the sagittal plane for the purpose of visualizing any disruption
in the lamellar structure of the anulus fibrosus. The disc and half
the adjacent vertebral bodies were cut from each frozen motion segment.
This vertebral body-disc-vertebral body unit the was cut into parasagittal
sections 5 mm thick, using a saw to cut through the bone and a sharp
knife to cut through frozen disc tissue. Sections were photographed
under low-angle incident light to allow individual lamellae of the
anulus to be visualized.
Two of the authors (M.A., P.D.) assessed the slides independently
for the following features: inward (reverse) bulging of the inner
lamellae (midsagittal slices only) and outward bulging of the outward
lamellae beyond the farthest rim of the vertebral body. Bulging
was quantified by dividing the maximum horizontal displacement of
a lamella's path by the vertical distance between its end points.
Features were considered as present only if both authors noted them
independently. It was not possible to assess control (unloaded)
discs in a similar manner because all available motion segments
were tested, and the intervening discs were cut in the horizontal
plane during dissection.
The remaining 23 discs were sectioned in the horizontal plane for
comparison with discs tested previously in the author's laboratory
(6,7) The precise nature of endplate damage was not investigated
because this would have required defatting procedures, which would
have interfered with the investigations of the disc. The nature
of endplate damage in cadaver specimens subjected to compressive
overload has been investigated thoroughly by others (20).
Matched-pair t tests were used to examine differences in intradiscal
stress distributions at various stages of the experiments. One-tailed
tests were used because the direction of changes could be anticipated
from previous work (11-13,56). Single and linear regression procedures
were used to test for the dependence of intradiscal stresses on
continuous variables such as age and damage severity. Differences
cited later were all highly significant (P < 0.005) unless stated
Compressive damage occurred at 6.7 +/- 2.5 kN (range, 3-11.6 kN),
resulting in permanent height loss of 0.72 +/- 0.39 mm (range, 0.17-2.11
mm), which is equivalent to approximately 1% of motion segment height.
Subsequent sectioning showed that compressive failure involved cracking
of a vertebral endplate, the trabeculae supporting it, or both,
sometimes accompanied by vertical displacement of some nucleus pulposus
into the vertebral body, as described previously (13,19,20,71).
One specimen failed by posterior prolapse of the disc. It is unusual,
but not rare, for discs to herniate in this way while positioned
in only moderate flexion, provide the compressive force is very
Compression damage caused an average fall of 25% +/- 27% in nucleus
pressure, and an average reduction of 25% +/- 26% in the maximum
vertical or horizontal compressive stress in the anterior anulus.
Maximum stresses in the posterior anulus, however, increased by
16% +/- 49% (P = 0.014). The height of stress "peaks" in the anulus
were defined relative to pressure in the nucleus: In the posterior
anulus, these peaks increased by 191%, from 0.45Mpa to 1.32Mpa,
after vertebral damage. The anteroposterior diameter of the hydrostatic
nucleus decreased from 53% to 40% after vertebral damage. The lateral
diameter of the nucleus presumably decreased also, although stress
profiles were not measured in this direction.
The fall in nucleus pressure depended on the severity of vertebral
damage, as indicated by specimen height loss. Nucleus decompression
also was more marked in discs 50 to 70 years of age. No significant
correlation was found between damage severity and age, and multiple
regression showed that the dependence of nucleus decompression on
age remained significant after correction for damage severity (P
= 0.007). Lumbar level had no significant effect on nucleus decompression.
The height increase of stress peaks in the posterior anulus after
vertebral damage was proportional to the fall in nucleus pressure
(R = 0.40; P = 0.14). Vertebral damage greatly affected a typical
middle-aged disc but had comparatively little effect on a young
Cyclic loading did not equalize stress distributions by causing
loose tissue to migrate regions of high stress to regions of low
stress. On the contrary, it made the stress peaks worse. Average
results for the 19 discs tested in the neutral posture showed that
vertebral damage decreased nucleus pressure from 1.76 to 1.41Mpa,
and cyclic loading also decreased it further to 1.23Mpa. Cyclic
loading also decreased the diameter of the hydrostatic nucleus,
from40% to 30% of the anteroposterior diameter (P = 0.015). It also
increased the small stress peaks in the anterior anulus from 0.08
to 0.20Mpa (P = 0.015). Stress peaks in the posterior anulus increased
from 1.31 to 1.45Mpa, but this failed to reach significance (P =
The effects of endplate damage and subsequent cyclic loading were
particularly large in lordotic postures: in 2 degrees extension,
stress peaks in the posterior anulus increased from 0.60 to 1.91Mpa,
and the fall in nucleus pressure was greater than in the neutral
posture. Flexion, however, reduced the posterior stress peaks and
tended to even up the maximum stresses in the anterior and posterior
anuli at all stages of the experiment. Even after damage and cyclic
loading, moderate flexion was able to restore an approximately normal
distribution of compressive stresses most discs.
Structural damage in the discs
Sagittal plane disc sections indicated inward bulging of the anulus
in 8of 15 discs, and of the posterior in 9 of 15 discs. Usually,
the same discs were affected anteriorly and posteriorly, and it
was most apparent in middle-aged that had the most greatly altered
stress profiles. Outward bulging of the outer anulus beyond the
farthest margins of the vertebral body rim was observed anteriorly
in 8 of 15 discs, and posteriorly in14 of 15 discs. In 11 of these
14 discs, the "hairpin" bulging of the posterior lamellae was so
pronounced that horizontal displacement of the lamellae exceeded
their vertical height.
Surprisingly, the patterns of structural disruption showed no significant
dependence on whether the cyclic loading had been in flexion or
extension. Two discs (not including the disc that prolapse when
overloaded in compression) showed complete radial fissures in the
posterior anulus, and in one of these discs, it appeared that some
nucleus pulposus had migrated down the fissure during the period
of cyclic loading. Horizontal sectioning of the remaining 23 discs
showed that the anulus often portrayed the bell-shaped deformation
reported previously (6).
These experiments showed that minor compressive damage to a middle-age
lumbar vertebra sufficient to reduce motion segment height by approximately
1% causes large and progressive changes in the internal stress distribution
of adjacent intervertebral discs. Additional evidence suggested
that during subsequent cyclic loading, the lamellae could buckle
in towards the nucleus, or outward beyond the edge of the vertebral
body, and that the disrupted lamellae could allow migration of nucleus
The latter inferences were not supported by observations on control
(unloaded) discs, so there is no proof that the lamellae in these
discs were not disrupted before testing began. However, previous
postmortem studies have reported that inward collapsing lamellae
become common only in elderly discs (36,77), whereas more than half
the discs in the current study were affected, although most were
younger than 60 years of age. Also, the fact that the abnormalities
in stress distributions were made worse by the cyclic loading rather
than better suggested that a progressive mechanical failure had
been initiate in the discs.
The underlying mechanism of internal disc disruption is probably
as follows: The damaged endplate deforms more when under load (22),
allowing more space for the hydrated nucleus pulposus, or allowing
some nucleus tissue to pass through it. The nucleus therefore experiences
a reduction in pressure (23), which is similar in amount to the
reduction seen in degenerated discs (12,24) the decompressed disc
bulges more and losses height (24). This process is intensified
by water loss after sustained loading (10). Less of the applied
compressive force is resisted by the decompressed nucleus, so more
must be resisted by the surrounding anulus (and apophyseal joints).
High stress gradients in the anulus then force the inner lamellae
inward toward the decompressed nucleus (75) and the outer lamellae
outward. The buckling of the lamellae is encouraged by the accompanying
loss in disc height. The effects are greater in older discs because
there tissues are less hydrated, and therefore less able to deform
sufficiently to reduce steep stress gradients. Nucleus pulposus
material can move into the disrupted anulus during repetitive loading,
but bulk extrusion of nucleus pulposus from the disc can be achieved
(in vitro) only if the motion segment is heavily loaded in flexion
or hyperflexion (7,25,57). If endplate damage has similar consequences
in living people, then a mechanical explanation exists for the typical
structural features of disc degeneration. The validity of cadaveric
experiments was considered in detail previously (2). It was concluded
that the extremely low cell density, and metabolic rate of human
discs, and the relatively small effects of frozen storage on motion
segments (70) and intradiscal pressure (65) enable the results of
short-term mechanical experiments to be extrapolated to living people
with some confidence. Evidence that frozen storage affects disc
water content (43) or creep properties (14) may be attributable
to artifactual swelling of freeze-thawed discs after removal of
the ligamentum flavum, which normally pre-stresses the disc (54).
Any postmortem changes in disc hydration must be small because hydration
naturally varies by 20% during the course of each day, and similar
variation is observed in cadaver discs subjected to prolonged creep
loading (54). Freezing appears to cause some permanent change in
pig discs (14), which have a water content of 90%, but this may
not apply to less hydrated discs. Apparent changes in the creep
properties of discs immediately after death (47) are caused, at
least in part, by the poor reproducibility of the measurements even
before death (1). Diurnal fluid flow in vitro may prevent fatigue
damage from accumulating as quickly as in cadaver experiments, but
this possibility has not been investigated. The complex loading
of discs in life, which comes from gravity and muscle attachments,
can be simulated in cadaveric experiments by summing all of the
relevant forces into one "resultant" force, provided its magnitude,
direction, and point of application are chosen appropriately (9).
The only assumptions required are quite justifiable (2), so there
appears to be no reason why cadaver experiments should not be used
to simulate short-term mechanical changes in living discs.
In the longer term, However, mechanical events would be accompanied
by biologic events, as disc cells respond to changes in their mechanical
environment. Tissue culture experiments show that abnormally high
and abnormally low hydrostatic pressure both inhibit disc cell metabolism
(38,42) and that pressures of 3 Mpa can stimulate the production
of the matrix-degrading enzyme MMP3 (38).
In the current experiments, structural disruption to the endplate
and anulus reduced the ability of the disc to distribute compressive
stresses evenly, especially in lordotic postures, so regions of
very high and very low stress were generated. A large pressure drop
in the nucleus pulposus would inhibit cells in the nucleus from
synthesizing more proteoglycans and restoring the volume of the
nucleus. On the contrary, nucleus volume, and therefore pressure,
probably would fall even more, exacerbating the short term effects
simulated in the current experiments. In the anulus, peak stresses
often exceeded 3Mpa, and these would be expected to inhibit disc
cell metabolism and hinder attempts to repair the collagen network.
Therefore, by destroying the disc's ability to equalize compressive
stress, structural failure would inhibit matrix synthesis permanently
and progressively both nucleus and anulus. A relatively minor injury
to a vertebral body, which might quickly heal, then would leave
a progressive long-term problem for the adjacent discs. Endplate
damage also could lead to disc degeneration by other means: for
example, by hindering metabolite transport from the vertebral body
into the nucleus (53), or by instigating an inflammatory (35,68,80)
or autoimmune (17) reaction in the disc or the vertebral body (78).
There is plenty of circumstantial evidence linking endplate damage
with disc degeneration. According to Vernon-Roberts (81), discs
with Schmorl's nodes tend to exhibit advanced degenerative changes
at an earlier age, and the earliest changes are adjacent to the
endplate defect. In a large MRI study, Hamanichi et al (37) showed
that Schmorl's nodes were present in 19% of patients with back or
leg pain, as compared with 9% of controls. These authors found Schmorl's
nodes to be particularly common in patients ages 10 to 39 years,
and 60 to 69 years. The nodes were often associated with posterior
disc prolapse, especially at the lower lumbar levels. It is possible
that long-term biochemical changes may render old Schmorl's nodes
"invisible" to MRI scans in later life.
Schmorl's nodes at more than one level were a frequent finding (37).
In young people, they were associated with vigorous sports, suggesting
that they may be caused by an impulsive force acting up the spine.
The fact that Schmorl's nodes in young people often are of little
clinical relevance may be explained by the increased ability of
young discs to equalize compressive stress after endplate damage.
Associations between recently occurring endplate damage in middle
aged people and subsequent disc degeneration have yet to be explored.
The mechanical initiation of disc degeneration suggested by the
current study complements previous biochemical and histologic investigation
of disc aging and degeneration. Biochemical aging, which begins
at birth, is manifested by increased fragmentation and loss of proteoglycans
(26), water loss (8), brown pigmentation (66), and changes in matrix
collagens (66). These changes occur earlier and to a greater extent
in the nucleus than in the anulus, and they may be attributable
to "oxidative stress" arising from nutritional compromise (66,67).
In contrast, the types of structural disruption studied in the current
experiment tend to appear later, usually after the age of 20 years,
and they affect primarily the endplate and the anulus (66,81). Moreover,
in adults, disc herniation and endplate defects show little correlation
with age (83) and they most commonly affect only the lower lumbar
levels. It therefore appears that structural disruption of discs
should not be viewed simply as a more-or-less inevitable extension
of age-related changes.
In combination, the biochemical and mechanical evidence suggests
that disc "degeneration" represents some mechanical, or possibly
nutritional, injury superimposed on normal tissue aging. It may
be significant that Type 1 collagen, associated with tissues subjected
to non-hydrostatic stresses, appears in the nucleus pulposus only
after the age when gross structural damage is common (66). This
again suggests that mechanical events drive the biochemical changes
because a marked reduction in the size of the hydrostatic nucleus
was seen after the structural disruption produced in the current
experiments whereas little change in nucleus size followed (creep-induced)
loss of water from the disc (10). The relative importance of metabolic
and mechanical "injuries" as initiators of disc degeneration is
difficult to determine because they interact with each other and
with genetic inheritance. For example, cigarette smoking, which
probably impairs metabolite transport into the discs, increases
the risk of degeneration (15), but some of this small risk may be
attributable to generic inheritance and shared early environment
in families of smokers rather than the cigarette smoke itself (15,16).
Nevertheless, the fact that structural degenerative changes are
much more common in the lower lumbar discs than in the upper discs
(83), although they would have similar nutritional problems, suggests
that "nutritional" injuries are less important than mechanical injuries.
Regular physical activity appears to reduce or increase the risks
of disc degeneration, depending on how severe it is. This complication
probably is caused by the ability of skeletal tissues to strengthen
with regular moderate exercise (51) but to experience (fatigue)
failure if the loading is too severe (86). "Adaptive remodeling"
in response to controlled exercise explains why professional tennis
players have 30% more bone in their racquet arm (44), and why physically
active individuals have extremely strong vertebrae (33,34) and discs
(73). Conversely, a lack of exercise leads to tissue weakening,
and this may explain why some sedentary occupations increase the
risk of disc prolapse (49). The weakened spinal tissues would be
vulnerable to accidental injury during slips and falls.
Intervertebral discs may be particularly vulnerable to injury and
fatigue damage when they are subjected to sudden and large increases
in mechanical loading because increased physical loading will strengthen
muscles and bone faster than the avascular discs (3). These considerations
could explain why the highest known risk factors for disc prolapse
involve frequent lifting of heavy loads, either at work (49) or
in the home (61), although some manual occupations carry no greater
risk than sedentary work (48).
The mechanisms discussed earlier suggest how disc degeneration might
be initiated by structural disruption to the vertebral end plate.
However, is there biomechanical evidence to show that many people
overload their backs sufficiently to damage their vertebrae? In
post-menopausal women and elderly men, high forces are not always
necessary to cause endplate fractures: Many are reported to occur
during everyday activities, as shown in a recent review by Myers
(62). In younger people, a single overload injury could be caused
by a fall on the buttocks, or by maximal contraction of the trunk
muscles during exceptional circumstances. Vertebrae can be crushed
by muscle action during epileptic seizures (79), and a similar lack
of muscle inhibition may occur during alarming incidents (87), or
in the heat of sporting competition. Like other muscles, the erector
spinae are strongest when contracting eccentrically. They can generate
particularly high forces when preventing forced flexion of the trunk.
During repetitive activities, muscle action undoubtedly can lead
to fatigue failure of the vertebral endplate: In vitro, there is
a 70% risk of failure at approximately 40% to 50% of the specimen's
normal compressive failure load if 5000 loading cycles are applied
(19), which is only 3 to 4 kN for average young men (20.71). For
comparison, the peak compressive force on the spine rises to approximately
4.4 kN when weights of 20 kg are lifted from the ground (29). It
appears that only the adaptive remodeling process prevents all workers
in heavy manual jobs from sustaining fatigue damage to their vertebrae,
and the likelihood of an individual being injured will depend on
metabolic factors as much as the rigors of the job. Not surprisingly,
minor damage to the vertebral body endplate or to its supporting
trabeculae are very common (21,40,82), and may explain why endplates
become more concave with increasing age (21).
The aforementioned evidence explains how high or repetitive compressive
loading might initiate lumbar disc degeneration. Other explanations
are possible, such as hyperflexion injury (7) or defects in the
vitamin D receptor gene (84), and it is reasonable to suppose that
several factors may contribute to disc degeneration in individual
cases. However, repetitive may prove to be the factor that can be
controlled most easily. Effective control does not mean simply minimizing
spinal loading, because that would lead to weak backs that are vulnerable
to accidents. Manual handling legislation should recognize that
mechanical and metabolic risks interact, so that too little physical
exertion may be as harmful as too much. Also, mechanical risk factors
themselves can be environmental or genetic, so a given work activity
may harm one back but strengthen another. Links between disc degeneration
and back pain are also complicated, as discussed in the introductory
paragraphs. However, it would be unfortunate if mechanical explanations
of disc degeneration and back pain were abandoned simply because
they are not as simple as was first supposed.
Minor compressive damage to the vertebral body endplate alters
the distribution of matrix compressive stress in the adjacent intervertebral
disc. The nucleus is decompressed, and stress peaks appear in the
anulus. Discs 50 to 70 years of age are affected the most, presumably
because they have a reduced capacity to deform and equalize compressive
stress. Subsequent loading does not reverse the changes in intradiscal
stress. It makes them worse. Repetitive loading after endplate damage
appears to cause buckling of the lamellae of the anulus: The inner
anulus can collapse inward and the outer lamellae bulge outward,
particularly in the posterior anulus. Nucleus pulposus tissue can
migrate into and through the disrupted lamellae.
In life, the altered matrix stresses would be expected to inhibit
disc cell metabolism, so that a progressive biologic reaction to
the structural disruption would occur.
- Intervertebral disc degeneration involves structural disruption
and cell-mediated changes in composition, but it is not clear
which comes first.
- This experiment on cadaveric motion segments showed that compressive
damage to the vertebral body endplate alters the distribution
of matrix compressive stress in the adjacent intervertebral
disc. The nucleus is decompressed, and stress peaks appear in
- Subsequent cyclic loading made these changes worse, and there
was some evidence to suggest that the anulus was collapsing
gradually into the decompressed nucleus.
- Previous tissue culture experiments suggest that the altered
stress distributions would adversely affected disc cell metabolism.
Adams MA. Letter to the Editor. Proc Inst Mech Eng 1995;209:135.
Adams MA. Mechanical testing of the spine: An appraisal of Methodology,
results and conclusions. Spine1995;20:2151-6.
Adams MA, Dolan P. Could sudden increases in physical activity cause
intervertebral disc degeneration? Lancet 1997;350:734-5.
Adams MA, Dolan P, Hutton WC. The lumbar spine in backward bending.
Adams MA, Dolan P, Hutton WC. The stages of disc degeneration as
revealed by discograms. J Bone Joint Surg (Br)1986;68:36-41.
Adams MA, Hutton WC. Gradual disc prolapse. Spine 1985;10:524-31.
Adams MA, Hutton WC. Prolapsed intervertebral disc: A hyperflexion
injury. Spine (82;7:184-91.
Adams MA, Hutton WC. The effect on posture on the fluid content
of lumbar intervertebral discs. Spine 1983;8:665-71.
Adams MA, Hutton WC, Stott JRR. The resistance to flexion of the
lumbar intervertebral joint. Spine 1980;5:245-53.
Adams MA, McMillan DW, Green TP, Dolan P. Sustained loading generates
stress concentrations in lumbar intervertebral discs. Spine 1996;21:434-8.
Adams MA, MacNally DS, Chinn H, Dolan P. Posture and the compressive
strength of the lumbar spine. Clin Biomech 1994;9:5-14.
Adams MA, MacNally DS, Dolan P. Stress distributions inside intervertebral
discs: The effects on age and degeneration. J Bone Surg (Br) 1996;78:965-72.
Adams MA, MacNally DS, Wagstaff J, Goodship AE. Abnormal stress
concentrations in lumbar intervertebral discs following damage to
the vertebral body: A cause of disc failure. Eur Spine J 1993;1:214-21.
Bass MC, Duncan NA, Hariharan JS, Dusik J, Bueff HU, Lotz JC. Frozen
storage affects the compressive creep behaviour of the porcine intervertebral
disc. Spine 1997;22:2867-76.
Battie MC, Haynor DR, Fisher LD, Gill K, Gibbons LE, Videman T.
Similarities in degenerative findings on magnetic resonance images
of the lumbar spines of identical twins. J Bone Surg (Am) 1995;77:1662.
Battie MC, Videman T, Gibbons LE, et al. Determinants of lumbar
disc degeneration: A study relating to lifetime exposures and MRI
findings in identical twins. Spine 1995;20:2601-12.
Bogduk N. Clinical Anatomy of the Lumbar Spine and Sacrum. 3rd ed.
Churchill Livingston, 1997. ISBN 0-443-06014-2.
Boos N, Rieredr R, Schade V, Spratt KF, Semmer N, Aebi M. The diagnostic
accuracy of MRI, work perception, and phsycosocial factors in identifying
symptomatic disc herniations. Spine 1995;20:2613-25.
Brinckmann P, Biggermann M, Hilweg D. Fatigue fracture of human
lumbar vertebrae. Clin Biomech 1988;3 (suppl 1).
Brinckmann P, Biggermann M, Hilweg D. Prediction of the compressive
strength of human lumbar vertebrae. Clin Biomech 1989;4 (suppl 2).
Brinckmann P, Frobin W, Biggermann M, etal. Quantification of overload
injuries to thoracolumbar vertebrae and discs in persons exposed
to heavy physical exertions or vibration at the work place: Part
1. The shape of vertebrae and intervertebral discs. Clin Biomech
1994;9 (suppl 1).
Brinckmann P, Frobin W, Hierholzer E, Horst M. Deformation of the
vertebral endplate under axial loading of the spine. Spine 1983;8:851-6.
Brinckmann P, Grootenboer H. Change of disc height, radial bulge,
and intradiscal pressure from discectomy: An in vitro investigation
on human lumbar discs. Spine 1991;16:641-6.
Brinckmann P, Horst M. The influence of vertebral body fracture,
intradiscal injection, and partial discectomy on the radial bulge
and height of human lumbar discs. Spine 1985;10:138-45.
Brinckmann P, Porter RW. A laboratory model of lumbar disc protrusion.
Buckwalter JA. Spine update: Aging and degeneration of the human
intervertebral disc. Spine 1995:20:1307-14.
Crean JKG, Roberts S Jaffray DC, Eisenstein SM, Duance VC. Matrix
metalloproteinases in the human intervertebral disc: Role in disc
degeneration and scoliosis. Spine 1997;22:2877-84.
Crock HV. Internal disc disruption: A challenge to disc prolapse
50 years on. Spine 1986;11:650-3.
Dolan P, Earley M Adams MA. Bending and compressive stresses acting
on the lumbar spine during lifting activities. J Biomech 1994;27:1237-48.
Dolan P, Mannion AF, Adams MA. Passive tissues help the back muscles
to generate extensor moments during lifting. J Biomech 1994;27:1077-85.
Dunlop RB, Adams MA, Hutton WC. Disc space narrowing and the lumbar
facet joints. J bone Joint Surg (Br) 1984;66:706-10.
Gordon SJ, Yang KH, Mayer PJ, Mace AH, Kish VL, Radin EL. Mechanism
of disc rupture: A preliminary report. Spine 1991;16:450-6.
Granhed H, Jonson R, Hansson T. the loads on the lumbar spine during
extreme weight lifting. Spine 1987;12:146-9
Granhed H, Jonson R, Hansson T. Mineral content and strength of
lumbar vertebrae: A cadaver study. Actua Orthop Scand 1989;60:105-9.
Gronbald M, Virri J, Ronkko S, et al. A controlled biomechanical
and immunohistochemical study of human synovial-type (Group 2) phospholipase
A2 and inflammatory cells in macroscopically normal, degenerated,
and herniated human lumbar disc tissues. Spine 1996;21:2531-8.
Gunzburg R, Parkinson R, Moore R, et al. A cadaveric study comparing
discography, MRI, Histology, and mechanical behaviour of the human
lumbar disc. Spine 1992;17:417-23.
Hamanishi C, Kawabata T, Yosii T, Tanaka S. Schmorl's nodes on MRI:
Their incidence and clinical relevance. Spine 1994;19:450-3.
Handa T, Ishihara H, Ohshima H, Osada R, Tsuji H, Obata K. Effects
of hydrostatic pressure on matrix metalloproteinase production in
the human lumbar intervertebral disc. Spine 1997;22:1085-91.
Hansson TH, Keller T, Spengler D. mechanical behaviour of the human
lumbar spine:2. Fatigue strength during dynamic compressive loading.
J Orthop Res 1987;5:479-87.
Hilton RC, Ball J, Benn T. Vertebral endplate lesions (Schmorl's
nodes) in the dorsolumbar spine. Ann Rheum Dis 1976;35:127-32.
Hirsch C, Schajowicz F. Studies on structural changes in the lumbar
anulus fibrosus Acta Orthop Scand 1953;22:184-231.
Ishihara H, MacNally DS, Urban JPG, et al. Effects of hydrostatic
pressure on matrix synthesis in different regions of the intervertebral
disc. J Appl Physiol 1996;80:839-46.
Johnstone B, Urban JPG, Roberts S, Menage J. The fluid content of
the human intervertebral disc: Comparison between fluid content
and swelling pressure profiles of discs removed at surgery and those
taken at post mortem. Spine 1992;17:412-6.
Jones HH, Priest JD, Hayes WC, Tichenor CC, Nagel DA. Humeral hypertrophy
in response to exercise. J Bone Joint Surg (Am) 197;59:204-8.
Kaapa E, Han X, Holm S, et al. Collagen synthesis and types 1,3,4
and 6 collagens in an animal model of disc degeneration. Spine 1995;20:59-67.
Kang JD, Stefanovic-Racic M, McIntre LA, georgescu HI, Evans CH.
Towards a biomechanical understanding of human intervertebral disc
degeneration and herniation. Spine 1997;22:1065-73.
Keller TS, Holm SH, Hansson TH, Spengler DM, The dependence of intervertebral
disc mechanical properties on physiologic conditions. Spine 1990;15:751-61.
Kelsey JL. An epidemiological study of the relationship between
occupations and acute herniated lumbar intervertebral discs. Int
J Epidemiol 1975;4:197-205.
Kelsey JL, Githens PB, White AA, Holford TR, et al. An epidemiological
study of lifting and twisting on the job and risk for acute prolapsed
lumbar intervertebral discs. J Orthop Res 1984;2:61-6.
Kuslich SD Ulstrom CL, Michael CJ. The tissue origin of low back
pain and sciatica. Orthop Clin North Am 1991;22:181-7.
Lanyon LE, Goodship AE, Pye CJ, MacFie JH. Mechanically adaptive
bone remodeling. J Biomech 1982;15:141-54.
Markolf KL, Morris JM. The structural components of the intervertebral
disc. J Bone Surg (Am) 1974;56:141-54.
Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved
in the nutrition of the human lumbar intervertebral discs: Cellularity
and diffusion of glucose in vitro. J anat 1975;120:113-30.
MacMillan DW, Garbutt G, Adams MA. The effect of sustained loading
on the water content of the intervertebral disc: Implications for
disc metabolism. Ann Rheum Dis 1996;55:880-7.
MacMillan DW, McNally DS, Garbutt G, Adams MA. Stress distributions
inside intervertebral discs: the validity of experimental stress
profilometry. Eng Med 1996;210:81-7.
McNally DS, Adams MA. Internal intervertebral disc mechanics as
revealed by stress profilometry. Spine 1992;17:66-73.
McNally DS, Adams MA, Goodship AE. Can intervertebral disc prolapse
be predicted by disc mechanics? Spine 1993;18:1525-30.
McNally DS, Adams MA, Goodship AE. Development and validation of
a new transducer for intradiscal pressure measurement. J Biomed
McNally DS, Shackleford IM, Goodship AE, Mullholland RC. In vitro
stress measurements can predict pain on discography. Spine 1996;21:2580-7.
Moneta GB, Videman T, Kaivanto K, et al. Reported pain during lumbar
discography as a function of anular ruptures and disc degeneration.
Mundt DJ, Kelsey JL, Golden AL, et al. An epidemiologic study of
non-occupational lifting as a risk factor for herniated lumbar intervertebral
disc. Spine 1993;18:595-602.
Myers ER, Wilson SE. Biomechanics of osteoporosis and vertebral
fracture. Spine 1997;22:25S-31S.
Nachemson AL. Disc pressure measurements. Spine 1981;6:93-7.
Nachemson AL. In vitro discometry in lumbar discs with irregular
nucleograms. Acta Ortho Scand 1965;36:418-34.
Nachemson AL. Lumbar intradiscal pressure. Acta Ortho Scand 1960
Nerlich AG, Schleicher ED, Boos N. Immunohistologic markers for
age related changes of human lumbar intervertebral discs. Spine
Ohshima H, Urban JPG. The effect of lactate and pH on proteoglycan
synthesis rates in the intervertebral disc. Spine 1992;17:1079-82.
Olmarker K, Blomquist J, Stromberg J, Nannmark U, Thomsen P, Rydevik
B. Inflammatogenic properties of nucleus pulposus. Spine1995;20:665-9.
Osti OL, Vernon-Roberts B, Fraser RD. Anulus tears and intervertebral
disc degeneration: An experimental study using an animal model.
Panjabi MM, Krag M, Summers D, Videman T. Biomechanical time-tolerance
of fresh cadaveric human spine specimens. J Ortho Res 1985;3:292-300.
Perey O. Fracture of the vertebral endplate: A biomechanical investigation.
Acta Orthop Scand 1957 (suppl 25).
Pfeiffer M, Gris P, Franke P, et al. Degeneration model of the porcine
lumbar motion segment: Effects of various intradiscal procedures.