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Biomechanical implications of degenerative joint disease in the apophyseal joints of human thoracic and lumbar vertebrae.

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AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 136:318–326 (2008)
Biomechanical Implications of Degenerative Joint
Disease in the Apophyseal Joints of Human
Thoracic and Lumbar Vertebrae
Kate Robson Brown,1* Phill Pollintine,2 and Mike A. Adams2
1
2
Department of Archaeology and Anthropology, University of Bristol, Bristol BS8 1UU, UK
Department of Anatomy, University of Bristol, Bristol BS2 8EJ, UK
KEY WORDS
apophyseal joint; cartilage loss; joint disease; loading; biomechanics
ABSTRACT
An experimental technique for quantifying load-sharing in cadaveric spines is used to test the
hypothesis that degenerative changes in human apophyseal joints are directly related to high levels of compressive load-bearing by these joints. About 36 cadaveric thoraco-lumbar motion segments aged 64–92 years
were subjected to a compressive load of 1.5 kN. The distribution of compressive stress was measured in the
intervertebral discs using a miniature pressure transducer, and stress measurements were summed over
area to give the compressive force resisted by the disc.
This was subtracted from the applied 1.5 kN to indicate
compressive load-bearing by the apophyseal joints. The
cartilage of each apophyseal joint surface was then
graded for degree of degeneration. After maceration,
each joint surface was scored for degenerative joint disease (DJD) affecting the bone. Results demonstrated
that the apophyseal joints resisted 5–96% (mean 45%)
of the applied compressive force. A significant positive
correlation was demonstrated between age and cartilage
degeneration, age and DJD bone score, apophyseal joint
load-bearing and bone score, and cartilage score and
load-bearing. The latter correlation was strongest for
load-bearing above 50%. Ordinal regression showed that
the variables describing bone DJD (marginal osteophytes, pitting, bony contour change, and eburnation)
were significantly correlated with degree of cartilage
degeneration. It is concluded that in elderly individuals
apophyseal joint load-bearing above a threshold of 50%
is associated with severe degenerative changes in cartilage and bone, and that markers of DJD observed
palaeopathologically may be used as predictors of such
loading in life. Am J Phys Anthropol 136:318–326,
2008. V 2008 Wiley-Liss, Inc.
The extent to which degenerative joint disease (DJD)
in bone may be seen as an indicator of mechanical or
occupational stress has long been a focus of debate
within osteoarchaeology (e.g., Jurmain, 1991; Waldron,
1991; Knüsel et al., 1997; Sofaer Derevenski, 2000).
While some studies of paleopathology continue to use
DJD as a predictor of specific activity patterns (Gerszten
et al., 2001), most urge caution (Jurmain, 1990, 1991;
Bridges, 1991, 1994; Lovell, 1994; Knüsel et al., 1997).
Clinical studies have failed to demonstrate a simple relationship between DJD and specific patterns of movement
or activity (Lane et al., 1986; Videman et al., 1990, and
recently reviewed by Lequesne et al., 1997 and by Conaghan, 2002). Certain aspects of DJD appear to be related
to age (Rogers et al., 1987; Jurmain, 1991; Waldron,
1991, 1992; Knüsel et al., 1997), whereas others appear
to be related to sex, genetic inheritance, or body weight
(Merbs, 1983; Waldron, 1994; Maat et al., 1995; Sofaer
Derevenski, 2000; Meulenbelt et al., 2006). DJD is probably best thought of as resulting from a combination of
‘‘systemic’’ risk factors (which can lead to degenerative
changes to many joints within an individual) and localized factors which may be more closely related to the
mechanical loading experienced at a particular joint
(Kellgren and Lawrence, 1958). An additional complication is that skeletal tissues are able to strengthen in
response to mechanical loading which does not damage
them, so that moderate loading appears to be better for
the joints than either low or high loading (Videman et
al., 1990). Not surprisingly, this complexity has tended
to discourage consideration of the biomechanical implica-
tions of DJD, even where the presence and pattern of
such pathology is well documented (e.g., Weber and
Czarnetzki, 2002; Weber and Spring, 2004).
The vertebral column is one region of the skeleton
that has become a focus of interest for paleopathological
study into DJD. Comparative studies between species
have suggested that modern humans suffer vertebral
osteophytosis and osteoarthritis more commonly and
more severely than any other living primate, which
might support the view that bipedal posture and locomotion generate localized mechanical factors affecting the
spine that differ from those of other primate species
(Jurmain, 1990, 2000). Detailed study of the morphology
and distribution of degenerative changes in the human
spine suggest that complex interacting factors are
involved. For example, postmortem studies indicate that
traumatic flexion or torsion injury to the lumbar spine
C 2008
V
WILEY-LISS, INC.
C
Grant sponsors: BBSRC and University of Bristol Research
Fellowship.
*Correspondence to: Kate Robson Brown, Department of Archaeology and Anthropology, University of Bristol, Bristol BS8 1UU.
E-mail: kate.robson-brown@bristol.ac.uk
Received 25 July 2007; accepted 28 December 2007
DOI 10.1002/ajpa.20814
Published online 6 March 2008 in Wiley InterScience
(www.interscience.wiley.com).
VERTEBRAL FACET JOINT DEGENERATION
can damage the articular surfaces of the apophyseal
joints, possibly precipitating DJD (Adams and Hutton,
1981; Twomey et al., 1989), and the pattern of cartilage
damage may be indicative of the type of mechanical
overload involved (Swanepoel et al., 1995). Palaeopathological studies have suggested that DJD occurs in the
apophyseal joints of the cervical spine, which is subjected to relatively wide range of motion (Jurmain, 1977;
Knüsel et al., 1997) and also in the lower lumbar spine,
which is heavily loaded (Lewin, 1964; Jurmain, 1977;
Bridges, 1994; Knüsel et al., 1997; Sofaer Derevenski,
2000; Haefeli et al., 2006). It is not clear if DJD reflects
excessive movements, or loading, or both.
The situation can be further complicated by the adjacent intervertebral discs. Disc degeneration and narrowing increase compressive load-bearing by the apophyseal
joints (Dunlop et al., 1984; Adams et al., 2006), especially when specimens are loaded to simulate a lordotic
posture (Dunlop et al., 1984), and clinical studies confirm that lumbar disc degeneration increases the risk of
DJD in the apophyseal joints (Butler et al., 1990). Evidence from postmortem studies has led to speculation
that patterns of cartilage wear on the apophyseal joint
surfaces may reflect focal loading of these surfaces in
certain individuals and postures (Swanepoel et al., 1995;
Tischer et al., 2006). However, there is little firm evidence to support this suggestion.
Given this complex background, it is perhaps not surprising that DJD in the apophyseal joints is of uncertain
biomechanical relevance to palaeopathology. There has
recently been a call for experimentally tested and validated biomechanical models to enable skeletal function
to be inferred from skeletal morphology (Pearson and
Lieberman, 2004; Van der Merwe et al., 2006). The present study responds to this call by combining experimental biomechanics and quantitative osteoarchaeology in
order to investigate the mechanical implications of degenerative changes in human apophyseal joints. Direct
quantification of the compressive load transmitted by the
apophyseal joints is difficult, even in cadaveric specimens (el-Bohy et al., 1989), but it can be achieved indirectly, by calculating the compressive force transmitted
by the adjacent intervertebral disc (Pollintine et al.,
2004a,b; Adams et al., 2006). Here this technique will be
used to compare load-bearing in the apophyseal joints of
elderly cadavers with direct evidence of DJD in the same
joints, assessed from morphological changes in cartilage
and bone.
MATERIALS AND METHODS
Twenty-two cadaveric thoraco-lumbar spines aged 64–
92 years (mean 77.4 years, STD 8.5 years) were obtained
from post-mortem rooms and stored at 2208C until
required for testing. None of the individuals had a history of traumatic injury to the spine, or suffered any
long-term disease that might influence disc degeneration
or bone strength. Spines were subsequently thawed and
dissected into 36 ‘‘motion segments.’’ The motion segment, consisting of two whole vertebrae and the intervening soft tissues (disc and ligaments) is the smallest
repeating unit of the spine that preserves the intervertebral joints intact, and as such has been used extensively
for in-vitro modeling of the mechanical behavior of the
spine. The following ligaments were preserved: the anterior and posterior longitudinal ligaments, the supraspinous and interspinous ligaments, the ligamentum fla-
319
Fig. 1. Apparatus for measuring distributions of compressive ‘‘stress’’ in loaded cadaveric intervertebral discs. Different
postures could be simulated by adjusting the height of the rear
roller. Compressive stress was measured by means of a pressure
transducer side-mounted in a 1.3-mm diameter needle.
vum and the capsule ligaments of the left and right apophyseal joints. Overall within the study, all levels
between T9-T10 and L5-S1 were represented, but it was
not possible to obtain identical segments for each individual. The total number and range of segments
included in the study were constrained by availability
and practicality. Each motion segment was radiographed
prior to testing as a record of bone density and distribution and disc height (Adams et al., 1986).
Each motion segment was secured in two cups of dental
stone and loaded on a computer-controlled hydraulic
materials testing machine (Dartec Ltd., Stourbridge, UK)
as shown in Figure 1. The compressive force on the spine
is conventionally defined as that force which acts perpendicular to the mid-plane of the disc (the plane equidistant
from its endplates). By keeping this plane horizontal, we
ensured that only compression was applied.
Each specimen underwent 2 h of ‘‘creep,’’ during which
a constant compressive force of 1.5 kN was applied. This
was used to reduce disc height and water content by an
amount similar to that which occurs in life during the
first few hours of each day in response to moderate physical activity (McMillan et al., 1996).
To obtain the compressive force transmitted by the
apophyseal joints, it was first necessary to calculate the
compressive load transmitted by the intervertebral disc
and adjoining vertebral bodies. As a first step, the distribution of compressive stress within the disc was measured by stress profilometry, as described in detail elsewhere (Adams et al., 1996; Pollintine et al., 2004a,b.
Briefly, each motion segment was subjected to a static
compressive load of 1.5 kN to represent the combined
effects of muscle tension and superincumbent body
weight during light manual labor (Nachemson, 1981;
Sato et al., 1999). During the loading period of 20 s, the
distribution of vertically acting compressive stress (force
per unit area) was measured inside the disc by pulling a
miniature strain-gauged pressure transducer (Gaeltec,
Dunvegen, Scotland) through the disc along its mid-sagittal diameter (see Fig. 1). Stress profiles were obtained
with the motion segment positioned in 28 of extension to
simulate the lordotic erect standing posture (Adams
et al., 1988). The compressive stress distribution was then
integrated over crosssectional area to obtain the compressive force acting on the intervertebral disc. Subtracting this force from the applied 1.5 kN then indicates the
compressive force transmitted by the neural arch (effectively, the apophyseal joints: Adams and Hutton, 1980).
American Journal of Physical Anthropology
320
K.R. BROWN ET AL.
Validation tests have shown that this technique predicts
apophyseal joint load-bearing with errors of 2–8% (Pollintine et al., 2004a).
Following the completion of the biomechanical testing
phase of the project, the two vertebrae of each motion
segment were separated. The joint capsules were opened
dorsally and the inferior and superior articular processes
were carefully separated. In turn, the left and right apophyseal joint surfaces (LAP, RAP) were stained with Indian ink to reveal the degree of cartilage damage
(Meachim, 1972; Tischer et al., 2006). The presence and
severity of damage was recorded on a scale of 0–3, where
Grade 0 signified no damage, Grade 1 indicated moderate damage (minor or peripheral pits or fissures on an
otherwise normally shiny surface), Grade 2 indicated
severe damage (many fissures, severe pitting, thin and
rough surfaced cartilage remaining), and Grade 3 indicated complete cartilage loss.
After the cartilage had been scored, the remaining soft
tissue was removed by maceration. When completely dry,
the apophyseal joint articular surfaces were scored again
for pathological bone lesions. The following lesions were
recorded: distinct osteophytes, joint surface contour or
shape change, pitting, and eburnation. These changes
were each scored for presence and severity on a scale of
0–3, where 0 signified no lesions or bone change, 1 indicated moderate lesions or change, 2 indicated severe
lesions or change, and 3 indicated that very severe
change was observed. This grading system was based on
previously published descriptions and scoring schemes
(Sager, 1969; Resnick and Niwayama, 1988; Jurmain,
1990; Knüsel et al., 1997). Osteophytosis (OP) was
recorded as a proportion of the articular surface width,
based on the methodology of Knüsel et al. (1997). Articular surface width was measured using callipers, and the
proportion of that width presented by OP informed the
score. When OP was smaller than half the width and
less than 50% of the circumference of the margin
affected, a 1 was scored. If in excess of these values, but
lower than 75% of the width and margin the lesion was
recorded as a 2. A third category was included to account
for osteophytes larger than 75% of the joint surface width
or affecting more than 75% of the joint margin. Pitting
was recorded as 1 when less than half the articular surface was affected, as 2 when between 50 and 75% was
affected, and as 3 when more was affected. Similarly
eburnation was recorded as 1 when a small area of less
than half the articular surface was affected, as 2 when
between 50 and 75% was affected, and as 3 when more
was affected. Lesions were recorded independently for
each apophyseal joint, and to create an overall measure of
DJD for each, the four bone scores were summed to give
an overall score out of 12. There were no missing values.
To assess the strength of the relationships between
neural arch loading, age, cartilage scores, and bone
scores Spearman’s rank correlation was used. This
method is particularly useful for datasets which may not
meet the assumptions about normality and homoscedasticity required by linear regression correlation (SPSS,
Chicago, IL, version 12). Unless otherwise stated, each
segment was treated as an independent data point. In
the examination of the key relationship between apophyseal joint load-bearing and summed bone score a loess
curve was employed to present a locally weighted regression (Cleveland, 1979).
To investigate the effect of sex on summed bone score,
a Mann-Whitney U test was employed. The Mann-Whitney
American Journal of Physical Anthropology
U tests the null hypothesis that two samples are drawn
from the same population; it is a nonparametric alternative to the independent-samples t test. This rank sum
test is used when the normality assumption is questionable or when data are ordinal. One of the disadvantages
of nonparametric tests is their lower power compared to
their parametric equivalents when the assumptions
underlying the test are met, but the advantages are that
the test is not affected by outliers and is more suitable
for small datasets (Howell, 1996). To test the hypothesis
that summed bone score medians from the left and right
apophyseal joints are equal a Wilcoxon matched pairs,
signed ranks test was employed. This test is a nonparametric counterpart of the paired-samples t test.
To investigate the utility of the four constituent bone
score observations (marginal osteophyte, pitting, bony
contour change, eburnation) as predictors of cartilage
score, an ordinal logistic regression model was constructed. The ordinal logistic model is an extension of
the general linear model to ordinal categorical data. Cartilage score was taken as the dependent variable and the
reference category was Score 3.
Finally, the distribution of apophyseal joint degeneration across the spine was investigated by plotting the
mean bone score against spinal level. Mixed ANOVAs
were used to examine the interacting influences of
within-subject factors (spinal level) and between-subject
factors (age, sex) on apophyseal joint load-bearing, and
DJD degeneration scores.
RESULTS
Load-bearing results and DJD scores are summarized
in Table 1.
Results of the loading experiments demonstrate that
the apophyseal joints transmitted a measurable amount
of the compressive force applied. The proportion averaged 45% and ranged from 5 to 96% of the total compressive force (Table 1).
The mean and median summed bone score for the
female group (mean 5 4.09, SD 5 3.47, median 5 3.93)
was slightly higher than that of the male group (mean 5
3.43, SD 5 2.70, median 5 3.0). The Mann-Whitney U
test showed this difference not to be significant: U 5
619.5; exact P [ 0.05 (two-tailed) (Table 2). The Wilcoxon matched-pairs, signed ranks test showed that the
difference between the median summed bone score for
left (mean 5 3.56, SD 5 3.11, median 5 3.0) and right
(mean 5 3.92, SD 5 3.04, median 5 3.0) apophyseal
joints was not significant: exact P [ 0.05 (two-tailed). A
positive correlation was found between apophyseal joint
load-bearing and summed bone score (P \ 0.01) (Table 3
and Fig. 2). A marginally less strong correlation was
found between apophyseal joint load-bearing and cartilage score (P \ 0.01). Load-bearing was not found to correlate with age (Table 3). However, a positive correlation
was found between age and cartilage score (P \ 0.05),
and a stronger correlation was found between age and
summed bone score (P \ 0.01) (Table 3). Cartilage score
and bone score were also strongly positively correlated
(P \ 0.01) (Table 3).
The relationship between degree of cartilage loss and
the four constituents of observed bone change is presented as a matrix of correlations in Table 4. All four
variables describing bone changes (marginal osteophytes,
pitting, bony contour change, eburnation) are positively
321
VERTEBRAL FACET JOINT DEGENERATION
TABLE 1. Summarized results
Specimen
Age
Sex
Motion
seg
1
64
64
64
64
67
67
71
71
71
71
71
71
76
76
76
76
76
76
85
85
85
85
87
87
87
87
88
88
92
92
92
92
65
65
67
67
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
f
m
m
m
m
L2/L3
L2/L3
T12/L1
T12/L1
T12/L1
T12/L1
L2/L3
L2/L3
T12/L1
T12/L1
T10/T11
T10/T11
L2/L3
L2/L3
T12/L1
T12/L1
T12/L1
T12/L1
T11/T12
T11/T12
L2/L3
L2/L3
L2/L3
L2/L3
L4/L5
L4/L5
L4/L5
L4/L5
L3/L4
L3/L4
T12/L1
T12/L1
L2/L3
L2/L3
T11/T12
T11/T12
2
3
4
5
6
7
8
9
10
11
Joint
Na
load
Cart
score
Bone
score
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
41
41
33
33
65
65
5
5
65
65
85
85
40
40
49
49
30
30
48
48
64
64
96
96
96
96
70
70
86
86
36
36
50
50
54
54
1
1
1
1
1
1
1
2
0
1
2
3
1
2
1
0
1
1
1
1
3
3
2
3
3
3
2
2
1
2
1
2
1
1
2
2
2
2
0
0
1
2
2
3
1
1
3
6
4
6
0
0
2
2
3
4
9
10
8
8
11
11
9
8
5
5
1
2
2
4
1
1
Specimen
13
12
16
12
14
15
17
18
19
20
21
22
Age
Sex
Motion
seg
Joint
Na
load
Cart
score
Bone
score
67
67
72
72
72
72
72
72
72
72
72
72
72
72
74
74
79
79
81
81
81
81
81
81
82
82
82
82
89
89
90
90
90
90
90
90
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
L4/L5
L4/L5
L1/L2
L1/L2
T12/L1
T12/L1
T12/L1
T12/L1
T9/T10
T9/T10
L3/L4
L3/L4
L5/S1
L5/S1
T10/T11
T10/T11
L3/L4
L3/L4
L1/L2
L1/L2
L4/L5
L4/L5
T11/T12
T11/T12
T11/T12
T11/T12
L1/L2
L1/L2
T11/T12
T11/T12
L1/L2
L1/L2
L5/L6
L5/L6
T11/T12
T11/T12
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
LAP
RAP
9
9
12
12
81
81
10
10
37
37
34
34
13
13
81
81
15
15
28
28
33
33
50
50
74
74
27
27
71
71
10
10
20
20
10
10
2
2
1
2
1
2
1
1
0
1
1
2
1
0
3
2
2
2
2
3
1
1
3
3
2
3
1
2
2
2
2
2
1
1
0
1
4
4
2
3
6
6
0
1
0
1
2
3
0
0
10
10
6
4
5
3
4
4
6
7
8
9
3
3
3
2
3
3
2
2
0
1
Abbreviation: Motion seg, motion segment; T, thoracic vertebra; L, lumbar vertebra; LAP, left apophyseal joint; RAP, right apophyseal joint; Na load, % load transmitted by the neural arch; Cart score, cartilage score; Bone score, Summed DJD bone score.
and significantly correlated with degree of cartilage loss
(P \ 0.01). The ordinal logistic regression method was
used to model the relationship between cartilage score
and these four observed bone scores, whilst allowing for
age effects. The predictor (marginal osteophytes, pitting,
bony contour change, eburnation) was entered into the
model with cartilage score as the dependent variable,
and with the reference category as Score 3. A value of
P \ 0.05 (two sided) was considered significant (Norus̆is,
2005). The results of this analysis (Table 5) show that
for the category of marginal osteophytes, all scores are
significantly related to cartilage score. Specimens graded
low for marginal osteophytes are less likely to have high
scores for cartilage loss than specimens with high marginal osteophyte scores. For the category of pitting,
Scores 0 and 1 are significantly related to cartilage
score, although pitting Score 2 is not. So here, specimens
graded low (0 or 1) for pitting are less likely to have
high scores for cartilage loss than specimens a pitting
Score of 3, but pitting Score 2 is not a good predictor.
For the category of bony contour change, Scores 0 and 1
are strongly significantly related to cartilage score (P \
0.01) while Score 2 is lightly less strongly related (P \
0.05). For the category of eburnation, Score 0 is significantly related to cartilage score (P \ 0.01), and Score 1
is slightly less strongly related (P \ 0.05). In conclusion,
TABLE 2. Mann–Whitney U test for sexual differentiation
in summed bone score
Mann-Whitney U
Wilcoxon W
Z
Exact Sig. (two-tailed)
619.500
1399.500
20.273
0.788
low bone scores (0, 1) of all categories are good predictors
of low cartilage score, while high bone scores are more
likely to predict high cartilage scores.
Finally, to investigate any patterning of apophyseal
joint degeneration with spinal level within the whole
data set (all represented levels and all individuals), the
summed bone score was plotted against spinal level (see
Fig. 3). Here, the bone score represents the total score
for each parameter of bone degeneration, averaged for
left, right, and upper and lower articular processes.
Each box shows the median, quartiles (25–75%), and
extreme values (range).
Mixed ANOVAs were used to examine the interacting
influences of within-subject factors (spinal level) and
between-subject factors (age, sex) on apophyseal joint
load-bearing, and DJD degeneration scores. The withinsubject analysis showed that level was not associated
with neural arch loading (P 5 0.1) or apophyseal joint
American Journal of Physical Anthropology
322
K.R. BROWN ET AL.
TABLE 3. Spearman’s rank correlations between age, neural arch load-bearing, cartilage score, and summed bone score
Spearman’s rho
Age
Naload
Cartscore
Bonescore
a
b
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Age
Naload
Cartscore
Bonescore
–
0.112
0.347
0.252a
0.033
0.342b
0.003
.
0.349b
0.003
0.481b
0.000
.
0.737b
0.000
.
Correlation is significant at the 0.05 level (two-tailed).
Correlation is significant at the 0.01 level (two-tailed).
Fig. 2. Scatterplot showing the % apophyseal joint loadbearing against summed bone score, with the loess line marked.
degeneration (P 5 0.9). The between subject analysis
revealed that gender and age had no significant effect on
neural arch loading and apophyseal joint degeneration
(P [ 0.1).
DISCUSSION
Apophyseal joints evidently play a major, but variable,
role in resisting compressive forces acting on the human
thoracolumbar spine. On average, they resisted 45% of
this force, but in particular specimens it could be as
much as 96% or as little as 5% (Table 1). This wide variation in levels of compressive load may be explained by
the degree of disc degeneration. In a previous study that
included the specimens described here, it was shown
that disc degeneration transfers compressive load bearing from the anterior vertebral body to the neural arch
in upright postures, but that this effect does not depend
on spinal level or sex (Adams et al., 2006). In the present
study, the results of the mixed ANOVA examining
within-subject factors suggest that apophyseal joint loadbearing and degeneration were not systematically influenced by the spinal level. However, distribution of apophyseal joint degeneration with spinal level across the
whole data set appears to reveal a pattern of peaks and
troughs (see Fig. 3), which may mask any systematic
trend within a single individual. The peaks of severity
across the whole group lie between T10-T11 and L2-L5.
This finding is consistent with previous work (Nathan,
1962; Sager 1969; Bridges, 1994; Roberts and Manchester, 1995; Knüsel et al.,1997).
American Journal of Physical Anthropology
The ‘‘compressive force’’ that may underlie this finding
is defined as the force acting down the long axis of the
spine, perpendicular to the mid-plane of the intervertebral disc at each spinal level. Compression dominates
spinal loading during vigorous activities, and arises primarily from tension in the paraspinal muscles (Dolan et
al., 1994) which tend to follow the curvature of the
spine. Even in simple standing postures, the need to stabilize the upright spine leads to high antagonistic activity of trunk muscles (Cholewicki et al., 1997), and considerable spinal compression (Sato et al., 1999). Shear
loading of the spine acts in a direction perpendicular to
the compressive force (i.e. parallel to the mid-plane of
the disc) and is resisted mainly by the articular surfaces
of the apophyseal joints (Cyron and Hutton, 1980). Shear
loading arises mainly from superincumbent body weight,
and so tends to be greatest in the lower lumbar spine,
where the discs are most inclined to the vertical. This
may explain the relatively large size of the lower lumbar
apophyseal joints (Davis, 1961). Lumbar apophyseal
joints also resist axial rotation (Adams and Hutton,
1981), and they couple axial rotation with lateral bending in a posture-dependent manner (Cholewicki et al.,
1996). Nevertheless, it is compressive loading that acts
on the apophyseal joints for most of the time in upright
posture, and which is applied to all spinal levels, and
this is why compressive loading is the focus of the present study.
Previous studies have suggested that mechanical loading may underlie the development of DJD in the lower
spine (e.g. Jurmain, 1977; Putz, 1985; Swanepoel et al.,
1995; Knüsel et al., 1997; Sofaer Derevenski, 2000), and
the results presented here provide more detailed evidence which helps to explain how this occurs, at least in
relatively elderly individuals (see Fig. 2). The loess curve
in this figure presents a locally weighted regression, and
at any particular point on the x axis it is determined
only by the points in that vicinity (Cleveland, 1979). Figure 2 suggests that specimens in which less than 50% of
the experimental compressive load was resisted by the
apophyseal joints did not show a strong relationship
between increasing load and increasing degeneration of
the apophyseal joints. However, where the apophyseal
joints resisted more than 50% of the compressive load,
bone changes in the apophyseal joints were much more
severe. This may imply that there is a compressive force
threshold under which the apophyseal joints can accommodate the force transmission, but over which degeneration of cartilage and (especially) bone becomes more
likely. There is experimental evidence that disc degeneration and narrowing can cause the apophyseal joints to
transmit compressive load by extra-articular impingement between the bony tips of the inferior articular proc-
323
VERTEBRAL FACET JOINT DEGENERATION
TABLE 4. Spearman’s rank correlations between age, cartilage score, and the four bone score categories
Spearman’s rho
Age
Cartscore
Marost
Pitting
Bonycont
Ebur
a
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Correlation coefficient
Sig. (two-tailed)
Age
Cartscore
Marost
Pitting
Bonycont
–
0.285a
0.000
0.224a
0.004
0.405a
0.000
0.287a
0.000
0.238a
0.002
–
0.636a
0.000
0.606a
0.000
0.610a
0.000
0.580a
0.000
0.595a
0.000
0.783a
0.000
0.475a
0.000
0.532a
0.000
0.478a
0.000
0.565a
0.000
Ebur
Correlation is significant at the 0.01 level (two-tailed).
TABLE 5. Ordinal regression analyses with cartilage score as
the dependent variable and marginal osteophytes, pitting,
bony contour change, and eburnation scores as the independent
factors, with Score 3 as the reference
Variable
Estimate
Std Error
Sig.
Marost 0
Marost 1
Marost 2
Pitting 0
Pitting 1
Pitting 2
Bonycont 0
Bonycont 1
Bonycont 2
Ebur 0
Ebur 0
Ebur 0
27.433
25.562
24.387
24.571
22.811
20.194
25.505
23.588
21.706
23.468
21.459
0.616
1.176
1.143
1.132
1.009
0.990
0.997
0.845
0.729
0.724
0.709
0.725
0.864
0.000
0.000
0.000
0.000
0.005
0.845
0.000
0.000
0.180
0.000
0.044
0.476
95% confidence
interval
29.748
27.802
26.606
26.549
24.751
22.149
27.162
25.018
23.125
24.857
22.880
1.078
to
to
to
to
to
to
to
to
to
to
to
to
25.137
23.321
22.168
22.593
20.871
1.760
23.848
22.158
20.287
22.079
20.037
2.310
esses and the laminae below (Dunlop et al., 1984). Such
load-transmission would largely by-pass the articular
surfaces, and may explain why high neural arch loadbearing in the present study was marginally more
closely associated with degenerative changes in the bone
than cartilage. Another factor involved in the development of DJD is age. Previous studies using a large number of specimens dispersed over a wide age range (19–
92years) showed that the compressive force resisted by
the apophyseal joints increased significantly with age
(P \ 0.005) (Pollintine et al., 2004a). However, there was
a large variation in the force resisted by the apophyseal
joints at any particular age (for example, at 79 years the
force resisted varied between 20 and 65%). The lack of
correlation between apophyseal joint loading and age
found in the present study may be due to the narrower
age range, combined with this variation in loading at
any particular age. However, Table 3 shows that while
age and load-bearing by the apophyseal joints are not
significantly correlated, markers of joint degeneration
such as cartilage loss and bone change clearly are. It is
possible that, with advancing years, senescent chondrocytes are less likely to activate so that cartilage damage
is more likely to accumulate (Martin and Buckwalter,
2003), subsequently causing lesions and other changes
in the underlying bone. Three categories of bone change—
pitting, the presence of marginal osteophytes, and eburnation—appear to be particularly good predictors of this
cartilage loss.
Fig. 3. Distribution of apophyseal joint degeneration with
spinal level for the whole data set. Each box shows the median,
quartiles (25–75%), and extreme values (range).
The results of the present study probably depend on
the manner in which mechanical loading was applied to
the cadaveric specimens. Each motion segment was
creep-loaded to reduce disc water content and height by
an amount similar to the normal diurnal variation seen
in life (Botsford et al., 1994), and this height loss is
known to increase compressive load-bearing by the apophyseal joints (Dunlop et al., 1984) Also, specimens were
tested in 28 of extension to simulate the erect standing
posture in which the ‘‘normal’’ lordosis (i.e. the lordosis
of an excised unloaded cadaveric lumbar spine) is
slightly increased (Adams et al., 1988). In moderately
flexed postures, the apophyseal joints resist very little
compressive force, even when the discs are narrowed
(Adams et al., 2006). In this way, the relationship
between DJD and spinal loading can be seen to depend
on posture, and the time of day. Load-sharing in the
spine is sensitive to small variations in posture and disc
height: for example, just 28 of backwards bending of a
motion segment increases stress concentrations within
the intervertebral discs by 16% (Adams et al., 2000),
reduces pressure in the nucleus pulposus by 10% (Adams
et al., 1994), and approximately doubles load-bearing by
the apophyseal joints (Adams and Hutton, 1980).
American Journal of Physical Anthropology
324
K.R. BROWN ET AL.
The results of this present experiment suggest that
DJD in the apophyseal joints of the elderly human thoracolumbar spine can be strongly suggestive of biomechanical environment in life. Even the observation of
mild DJD in this region is a good indicator of cartilage
loss on the articular surface, and therefore joint space
narrowing, and increased interfacet forces. Observation
of severe bone change in the spine of an archaeological
skeleton of similar age at death to those included in this
study may suggest that the apophyseal joints were bearing much of the compressive load on the vertebra, probably in a lordotic posture. This situation is known to
arise when intervertebral disc degeneration is severe,
and it is associated with a reduction in bone density in
the anterior vertebral body, and high bone density in the
apophyseal joints relative to the vertebral body (Swanepoel et al., 1995; Fugiwara et al., 1999; Gries et al.,
2000; Adams et al., 2006; Tischer et al., 2006). Other factors, such as variations in apophyseal joint morphology
within and between spines may also be important. Together, these results indicate a change in vertebral function and show how bone (in particular) responds to a
changing mechanical environment.
This study has demonstrated how pathological and
biomechanical data can be combined to reveal new
insights into a skeletal condition of interest to palaeopathology. This approach is relatively uncommon, as comparative cadaveric or clinical studies involving collaborative efforts across discipline boundaries may be difficult
to establish. It is also the case that for some aspects of
palaeopathological study clinical comparison may not
hold the key to archaeological interpretation (Roberts et
al., 1998). For studies of DJD, however, such an
approach provides an essential grounding (Rogers et al.,
1987; Dieppe et al., 1997; Pearson and Lieberman, 2004;
Roberts et al., 2006). Not only is the relationship
between cartilage and bone change exposed, but also the
experimental framework permits testing of specific biomechanical hypotheses related to human movement, posture, and activity widely discussed in more general
terms (e.g. Knüsel et al., 1997; Plochoki, 2002; Robson
Brown et al., 2002; Van der Merwe et al., 2006; Mays,
2006). This may be of significance to the study of human
remains from archaeological contexts in a number of
ways. It provides support for the palaeopathological
investigation of sex or age related differences in the participation of activities that involve significant compressive loading on the vertebrae (e.g. Merbs, 1983; Van der
Merwe et al., 2006), both within populations and
between them (Bennike, 1985; Kramar et al., 1990;
Bridges, 1994; Knüsel et al., 1997). Similarly, there may
also be implications for the assessment of vertebral pathology in extinct hominin populations. For example, degenerative changes have been observed on some of the
Hadar australopithecine vertebrae, particularly in the
thoracolumbar region (Robinson, 1972; Cook et al.,
1983). The relatively large size of the neural arch in australopithecines, coupled with the patterning of DJD
described, could be an indication that the apophyseal
joints played a significant role in resisting compressive
forces acting on the australopithecine thoracolumbar
spine, which in turn suggests intervertebral disc degeneration or lordotic posture, or both (Sanders, 1998; Whitcome et al., 2007). This possibility requires further investigation, but it is encouraging that while it may not be
possible to isolate a particular behavior or activity that
most stressed peoples’ bodies in life (Jurmain, 1990), the
American Journal of Physical Anthropology
comparative, experimental approach presented here can
nevertheless yield insights into human biomechanics in
archaeological populations.
CONCLUSIONS
Previous work has shown that human apophyseal
joints have a variable load-bearing function, which
increases following degeneration and narrowing of the
intervertebral discs, and in lordotic postures. The present study shows that in elderly individuals, when loadbearing exceeds 50% of the compressive force acting on
the spine, then degenerative changes are to be expected
in the apophyseal joints, particularly in the subchondral
bone. This suggests that load transmission is largely
extra-articular, between the tips of the inferior articular
processes and the laminae. The variables describing
bone change (pitting, marginal osteophytes, bony contour
change and eburnation) are positively and significantly
correlated with degree of cartilage loss, and therefore
may be seen as good palaeopathological predictors of
such soft tissue degeneration in elderly individuals.
ACKNOWLEDGMENTS
Many thanks to Chris Knüsel and the anonymous
reviewers for their thoughtful comments on previous
drafts of this article.
LITERATURE CITED
Adams MA, Hutton WC. 1980. The effect of posture on the role
of the apophyseal joints in resisting intervertebral compressive forces. J Bone Joint Surg (Br) 62:358–362.
Adams MA, Hutton WC. 1981. The relevance of torsion to the
mechanical derangement of the lumbar spine. Spine 6:241–
248.
Adams MA, Dolan P, Hutton WC. 1986. The stages of disc
degeneration as revealed by discograms. J Bone Joint Surg
(Br) 68:36–41.
Adams MA, Dolan P, Hutton WC. 1988. The lumbar spine in
backward bending. Spine 13:1019–1026.
Adams MA, May S, Freeman BJ, Morrison HP, Dolan P. 2000.
Effects of backward bending of lumbar intervertebral discs.
Relevance to physical therapy treatments for low back pain.
Spine 25:41–47.
Adams MA, McNally DS, Chinn H, Dolan P. 1994. Posture and
the compressive strength of the lumbar spine. Clin Biomech
9:5–14.
Adams MA, McNally DS, Dolan P. 1996. ‘‘Stress’’ distributions
inside intervertebral discs. The effects of age and degeneration. J Bone Joint Surg 78:965–972.
Adams MA, Pollintine P, Tobias JH, Wakley GK, Dolan P. 2006.
Intervertebral disc degeneration can predispose to anterior
vertebral fractures in the thoracolumbar spine. J Bone Miner
Res 21:1409–1416.
Bennike P. 1985. Paleopathology of Danish skeletons. A comparative study of demography, disease and injury. Copenhagen:
Akademisk Forlag.
Botsford DJ, Esses SI, Ogilvie-Harris DJ. 1994. In vivo diurnal
variation in intervertebral disc volume and morphology. Spine
19:95–940.
Bridges PS. 1991. Degenerative joint disease in hunter-gatherers and agriculturalists of the southeastern United States.
Am J Phys Anthropol 85:379–391.
Bridges PS. 1994. Vertebral arthritis and physical activities in
the prehistoric southeastern United States. Am J Phys
Anthropol 93:83–93.
Butler D, Trafimov JH, Andersson GB, McNeill TW, Huckman
MS. 1990. Discs degenerate before facts. Spine 15:111–113.
VERTEBRAL FACET JOINT DEGENERATION
Cholewicki J, Crisco JJ III, Oxland TR, Yamamoto I, Panjabi
MM. 1996. Effects of posture and structure on three-dimensional coupled rotations in the lumbar spine. A biomechanical
analysis. Spine 21:2421–2428.
Cholewicki J, Panjabi MM, Khachatryan A. 1997. Stabilizing
function of trunk flexor-extensor muscles around a neutral
spine posture. Spine 22:2207–2212.
Cleveland WS. 1979. Robust locally weighted regression and
smoothing scatterplots. J Am Stat Assoc 74:829–836.
Conaghan PG. 2002. Update on osteoarthritis part 1: current
concepts and the relation to exercise. Br J Sports Med 36:
330–333.
Cook DC, Buikstra JE, DeRousseau CJ, Johanson DC. 1983.
Vertebral pathology in the Afar australopithecines. Am J
Phys Anthropol 60:83–102.
Cyron BM, Hutton WC. 1980. Articular tropism and stability of
the lumbar spine. Spine 5:168–172.
Davis PR. 1961. Human lower lumbar vertebrae; some mechanical and osteological considerations. J Anat 95:337–344.
Dieppe PA, Cushnagan J, Shepstone L. 1997. The Bristol
‘‘OA500’’ Study: progression of osteoarthritis (OA) over 3
years and the relationship between clinical and radiographic
changes at the knee joint. Osteoarthritis Cartilage 5:87–97.
Dolan P, Earley M, Adams MA. 1994. Bending and compressive
stresses acting on the lumbar spine during lifting activities.
J Biomech 27:1237–1248.
Dunlop RB, Adams MA, Hutton WC. 1984. Disc space narrowing and the lumbar facet joints. J Bone Joint Surg (Br)
66:706–710.
el-Bohy AA, Yang KH, King AI. 1989. Experimental verification
of facet load transmission by direct measurement of facet lamina contact pressure. J Biomech 22:931–941.
Fugiwara A, Tamai K, Yamato M. 1999. The relationship
between facet joint osteoarthritis and disc degeneration of the
lumbar spine: an MRI study. Eur Spine J 8:396–401.
Gerszten PC, Gerszten E, Allison MJ. 2001. Diseases of the
spine in South American mummies. Neurosurgery 48:208–
213.
Gries NC, Berlemann U, Moore RJ, Vernon-Roberts B. 2000.
Early histological changes in lower lumbar discs and facet
joints and their correlation. Eur Spine J 9:23–29.
Haefeli MF, Kalberer F, Saegesser D, Nerlich AG, Boos N, Paesold G. 2006. The course of macroscopic degeneration in the
human lumbar intervertebral disc. Spine 31:1522–1531.
Howell DC. 1996. Statistical methods for psychology, 3rd ed.
Belmont California: Duxbury Press.
Jurmain RD. 1977. Stress and the etiology of osteoarthritis. Am
J Phys Anthropol 46:353–366.
Jurmain RD. 1990. Paleoepidemiology of a central California
prehistoric population from CA-ALA-329: II. Degenerative disease. Am J Phys Anthropol 83:83–94.
Jurmain RD. 1991. Degenerative changes in peripheral joints as
indicators of mechanical stress: opportunities and limitations.
Int J Osteoarchaeol 1:247–252.
Jurmain RD. 2000. Degenerative joint disease in African great
apes: an evolutionary perspective. J Hum Evol 39:185–203.
Kellgren JH, Lawrence JS. 1958. Osteo-arthrosis and disk
degeneration in an urban population. Ann Rheum Dis 17:
388–397.
Knüsel CJ, Göggel S, Lucy D. 1997. Comparative degenerative
joint disease of the vertebral column in the medieval monastic
cemetery of the Gilbertine Priory and St. Andrew, Fishergate,
York, England. Am J Phys Anthropol 103:481–495.
Kramar C, Lagier R, Baud CA. 1990. Rheumatic diseases in Neolithic and medieval populations of western Switzerland.
Zeitschrift f€
vr Rheumatol 49:338–345.
Lane NE, Bloch DA, Jones HH, Marshall WH, Wood PD, Fries
JF. 1986. Long-distance running, bone density and osteoarthritis. J Am Med Assoc 255:1147–1151.
Lequesne MG, Dang N, Lane NE. 1997. Sport practice and
osteoarthritis of the limbs. Osteoarthritis Cartilage 5:75–
86.
Lewin T. 1964. Osteoarthritis in lumbar synovial joints. A morphologic study. Acta Orthop Scand Suppl 73:1–112.
325
Lovell NC. 1994. Spinal arthritis and physical stress at Bronze
Age Harappa. Am J Phys Anthropol 93:149–164.
Maat GJR, Mastwijk RW, van der Velde E. 1995. Skeletal distribution of degenerative changes in vertebral osteophytosis, vertebral osteoarthritis and DISH. Int J Osteoarchaeol 5:289–298.
Martin JA, Buckwalter JA. 2003. The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J Bone Joint Surg Am 85A (Suppl 2):106–110.
Mays S. 2006. Spondylolysis, spondylolisthesis, and lumbo-sacral morphology in a medieval English skeletal population. Am
J Phys Anthropol 131:352–362.
McMillan DW, McNally DS, Garbutt G, Adams MA. 1996. Effect
of sustained loading on the water content of intervertebral
discs: implications for disc metabolism. Ann Rheum Dis
55:880–887.
Meachim G. 1972. Light microscopy of Indian ink preparations
of fibrillated cartilage. Ann Rheum Dis 31:457–464.
Merbs CF. 1983. Patterns of activity-induced pathology in a Canadian Inuit population. Ottawa: Archaeological Survey of
Canada. National Museum of Man, Mercury Series 119.
Meulenbelt I, Kloppenburg M, Kroon HM, Houwing-Duistermaat JJ, Garnero P, Hellio Le Graverand MP, Degroot J,
Slagboom PE. 2006. Urinary CTX-II levels are associated
with radiographic subtypes of osteoarthritis in hip, knee,
hand, and facet joints in subject with familial osteoarthritis at
multiple sites: the GARP study. Ann Rheum Dis 65:360–365.
Nachemson AL. 1981. Disc pressure measurements. Spine 6:93–
97.
Nathan H. 1962. Osteophytes of the vertebral column. J Bone
Joint Surg 44:243–268.
Norus̆is, MJ. 2005. SPSS 13.0 guide to data analysis. Englewood
Cliffs: Prentice Hall.
Pearson OM, Lieberman DE. 2004. The aging of Wolff ’s Law:
ontogeny and responses to mechanical loading in cortical
bone. Am J Phys Anthropol 125:63–99.
Plochoki JH. 2002. Directional bilateral asymmetry in human
sacral morphology. Int J Osteoarchaeol 12:349–355.
Pollintine P, Przybyla AS, Dolan P, Adams MA. 2004a. Neural
arch load-bearing in old and degenerated spines. J Biomech
37:197–204.
Pollintine P, Dolan P, Tobias JH, Adams MA. 2004b. Intervertebral disc degeneration can lead to ‘‘stress-shielding’’ of the anterior vertebral body: a cause of osteoporotic vertebral fracture? Spine 29:774–782.
Putz R. 1985. The functional morphology of the superior articular processes of the lumbar vertebrae. J Anat 143:181–187.
Resnick D, Niwayama G. 1988. Diagnosis of bone and joint disorders, 2nd ed. Washington DC: WB Saunders.
Roberts CA, Manchester KM. 1995. The archaeology of disease.
Gloucester: Cornell University Press.
Roberts CA, Boylston A, Buckley L, Chamberlain AC, Murphy
EM. 1998. Rib lesions and tuberculosis: the paleopathological
evidence. Tubercle Lung Dis 79:55–60.
Roberts AM, Robson Brown K, Musgrave JH, Leslie I. 2006. A
case of bilateral scapholunate advanced collapse in a RomanoBritish skeleton from Ancaster. Int J Osteoarchaeol 16:208–
220.
Robinson JT. 1972. Early hominid posture and locomotion. Chicago: University of Chicago Press.
Robson Brown KA, Davies EN, McNally DS. 2002. The angular
distribution of vertebral trabeculae in modern humans, chimpanzees and the Kebara 2 Neanderthal. J Hum Evol 43:189–
205.
Rogers J, Waldron T, Dieppe P, Watt I. 1987. Arthropathies in
palaeopathology: the basis of classification according to most
probably cause. J Archaeol Sci 14:179–193.
Sager P. 1969. Spondylosis cervicalis. Copenhagen: Munksgaard.
Sanders WJ. 1998. Comparative morphometric study of the australopithecine vertebral series Stw-H8/H41. J Hum Evol
34:249–302.
Sato K, Kikuchi S, Yonezawa T. 1999. In vivo intradiscal pressure measurement in healthy individuals and in patients with
ongoing back problems. Spine 24:2468–2474.
American Journal of Physical Anthropology
326
K.R. BROWN ET AL.
Sofaer Derevenski JR. 2000. Sex differences in activity-related
osseous change in the spine and the gendered division of labor
at Ensay and Wharram Percy, UK. Am J Phys Anthropol
111:333–354.
Swanepoel MW, Adams LM, Smeathers JE. 1995. Human lumbar apophyseal joint damage and intervertebral disc degeneration. Ann Rheum Dis 54:182–188.
Tischer T, Aktas T, Milz S, Putz RV. 2006. Detailed pathological
changes of human lumbar facet joints L1-L5 in elderly individuals. Eur Spine J 15:308–315.
Twomey LT, Taylor JR, Taylor MM. 1989. Unsuspected damage
to lumbar zygapophyseal (facet) joints after motor-vehicle
accidents. Med J Aust 151:210–212, 215–217.
Van der Merwe AE, I scan MY, L’Abbè EN. 2006. The pattern of
vertebral osteophyte development in a South African population. Int J Osteoarchaeol 16:459–464.
Videman T, Nurmine M, Troup JD. 1990. 1990 Volvo Award in
clinical sciences. Lumbar spinal pathology in cadaveric mate-
American Journal of Physical Anthropology
rial in relation to history of back pain, occupation, and physical loading. Spine 15:728–740.
Waldron T. 1991. The prevalence of, and the relationship
between, some spinal diseases in a human skeletal population
from London. Int J Osteoarchaeol 1:103–110.
Waldron T. 1992. Osteoarthritis in a Black Death cemetery in
London. Int J Osteoarchaeol 2:235–240.
Waldron T. 1994. Counting the dead: the epidemiology of skeletal populations. Chichester: Wiley.
Weber J, Czarnetzki A. 2002. Paleopathology of the lumbar
spine in the early medieval period. Z Orthop Grenzgeb 140:
637–643.
Weber J, Spring A. 2004. Degenerative changes of the cervical
facet joints in the medial and lateral atlantoaxial joint—a
paleopathological study. Z Orthop Grenzgeb 142:184–187.
Whitcome KK, Shapiro LJ, Lieberman DE. 2007. Fetal load and
the evolution of lumbar lordosis in bipedal hominins. Nature
450:1075–1080.
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