Lumbar disc degeneration is associated with modic change and high paraspinal fat content - A 3.0T magnetic resonance imaging study

Abstract

Background
Degenerative disc disease of the lumbar spine is common, with severe disease increasing the risk for chronic low back pain. This cross-sectional study examined whether disc degeneration is representative of a ‘whole-organ’ pathology, by examining its association with bone (vertebral endplate) and soft tissue (paraspinal muscle fat) abnormalities. Methods
Seventy-two community-based individuals unselected for low back pain, had Magnetic Resonance Imaging (MRI). Lumbosacral disc degeneration was determined via the Pfirrmann grading system, a validated method to assess the intervertebral disc, distinguishing the nucleus and annulus, the signal intensity and the height of the intervertebral disc. Modic change and high paraspinal muscle fat content was also measured from MRI. ResultsSevere disc degeneration was associated, or tended to be associated with type 2 Modic change from L2 to L5 (OR range 3.5 to 25.3, p ≤ 0.06). Moreover, severe disc degeneration at all intervertebral levels was associated with or tended to be associated with high fat content of the paraspinal muscles (OR range 3.7 to 14.3, p ≤ 0.09). Conclusion
These data demonstrate that disc degeneration of the lumbar spine is commonly accompanied by Modic change and high fat content of paraspinal muscles, thus representing a ‘whole-organ’ pathology. Longitudinal studies are required to determine the temporal relationship between these structural abnormalities. Understanding this may have the potential to identify novel targets for the treatment and prevention of lumbosacral disc degeneration.

Full text

R E S E A R C H A R T I C L E Open Access
Lumbar disc degeneration is associated
with modic change and high paraspinal fat
content –a 3.0T magnetic resonance
imaging study
Andrew J. Teichtahl
1,2
, Donna M. Urquhart
1
, Yuanyuan Wang
1
, Anita E. Wluka
1
, Richard O’Sullivan
3,4
,
Graeme Jones
5
and Flavia M. Cicuttini
1*
Abstract
Background: Degenerative disc disease of the lumbar spine is common, with severe disease increasing the risk for
chronic low back pain. This cross-sectional study examined whether disc degeneration is representative of a ‘whole-
organ’pathology, by examining its association with bone (vertebral endplate) and soft tissue (paraspinal muscle fat)
abnormalities.
Methods: Seventy-two community-based individuals unselected for low back pain, had Magnetic Resonance
Imaging (MRI). Lumbosacral disc degeneration was determined via the Pfirrmann grading system, a validated
method to assess the intervertebral disc, distinguishing the nucleus and annulus, the signal intensity and the height
of the intervertebral disc. Modic change and high paraspinal muscle fat content was also measured from MRI.
Results: Severe disc degeneration was associated, or tended to be associated with type 2 Modic change from L2
to L5 (OR range 3.5 to 25.3, p≤0.06). Moreover, severe disc degeneration at all intervertebral levels was associated
with or tended to be associated with high fat content of the paraspinal muscles (OR range 3.7 to 14.3, p≤0.09).
Conclusion: These data demonstrate that disc degeneration of the lumbar spine is commonly accompanied by
Modic change and high fat content of paraspinal muscles, thus representing a ‘whole-organ’pathology.
Longitudinal studies are required to determine the temporal relationship between these structural abnormalities.
Understanding this may have the potential to identify novel targets for the treatment and prevention of
lumbosacral disc degeneration.
Keywords: Lumbar, Intervertebral disc, Disc degeneration, Modic, Muscle, Fat
Background
Degenerative disc disease is common in the lumbar spine,
with one third of asymptomatic young women demonstrat-
ing abnormalities when assessed by Magnetic Resonance
Imaging (MRI) [1]. In a case-control study of older adults
with and without chronic low back pain, people with more
severe disc degeneration had a two-fold increased risk of
chronic low back pain than those without structural disc
abnormalities [2]. Similarly, in a cross-sectional study, low
back pain was found to be associated with several features
of disc degeneration (dark nucleous pulposus and posterior
and anterior bulge) [3].
Despite degenerative disc disease being considered to be
a common finding, epidemiological studies have used var-
ied measures to define disease. In histological studies
these include granular changes, tear and cleft formation,
chondrocyte proliferation, mucous degeneration and cell
death [4], while macroscopic grading systems incorporate
changes in the endplate and vertebral body, as well as nu-
cleus and annulus [5]. Radiographic studies class disc de-
generation by varying grades of joint space narrowing,
* Correspondence: flavia.cicuttini@monash.edu
1
Department of Epidemiology and Preventive Medicine, School of Public
Health and Preventive Medicine, Monash University, Alfred Hospital,
Melbourne, VIC 3004, Australia
Full list of author information is available at the end of the article
© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439
DOI 10.1186/s12891-016-1297-z
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

endplate sclerosis and osteophytes [6, 7], while MRI stud-
ies have focussed on individual features including tears in
the annulus [8], herniated nucleus [9] and height of the
intervertebral disc [10]. Pfirrmann’s method (2001) [11]
was endorsed as a valid and reliable method of assessing
intervertebral disc degeneration using MRI in a systematic
review of existing grading systems for lumbar disc degen-
eration [12]. The Pfirrmann system utilises a number of
MRI features including the appearance of the disc struc-
ture, the signal intensity, intervertebral disc height and the
distinction between the nucleus and the annulus, to give a
5 point grading system [11] (Table 1).
Although people with more severe disc degeneration
have an increased risk for chronic low back pain [2, 3],
whether disc degeneration is associated with other struc-
tural abnormalities is unclear. MRI has helped to better
understand degenerative joint pathology. For instance,
MRI studies of knee osteoarthritis have recognised that
deleterious cartilage changes are accompanied by bone
and soft tissue abnormalities, thus representing a ‘whole-
organ’disease [13]. Spinal degeneration has not been as
well examined, and whether akin to the changes in hyaline
cartilage in the knee, fibrocartilage degeneration of the
intervertebral disc is associated with whole-organ spinal
pathology is unclear. Vertebral endplate lesions (Modic
change) may be analogous to subchondral bone sclerosis
seen in osteoarthritis and may be an important association
with disc degeneration [14–21]. Moreover, changes in the
architecture of spinal musculature, in particular fat con-
tent [9, 22–26], may also be a key structural feature of
spinal degeneration.
The aim of this cross-sectional MRI study was to deter-
mine the associations between intervertebral disc
degeneration of the lumbar spine and Modic and para-
spinal muscle fat content.
Methods
Participants
Seventy-two community-based individuals were recruited
through local media and weight loss clinics as part of a
study of obesity and musculoskeletal health. Participants
were recruited without reference to whether they had or
did not have low back pain. Participants were excluded if
they had a history of malignancy, significant systemic con-
dition (e.g. cerebrovascular accident, movement disorder, or
connective tissue disease), or inability to understand
English. A further exclusion criterion was any contraindica-
tion to MRI. Participants gave written informed consent.
The study was approved by the Human Research Ethics
Committees of the Alfred Hospital and Monash University.
Magnetic resonance imaging
MRI (2011–2012) was performed using a 3.0-T magnetic
resonance unit (MAGNETOM Verio, A Tim System;
Siemens, Erlangen, Germany). The participants’were posi-
tioned in supine and the following scans were performed:
(1) sagittal T1 Turbo Spin Echo (TSE) imaging from T12
to the sacrum (time to recovery 670 ms; time to echo:
12 ms, slice thickness: 4 mm), (2) sagittal T2 TSE imaging
from T12 to sacrum (time to recovery: 3000–3600 ms; time
to echo: 87–114 ms, slice thickness: 4 mm), and (3) axial
T2 TSE imaging from L1 to S1 (time to recovery: 3000–
3600 ms; time to echo: 87–114 ms, slice thickness: 4 mm).
Different readers independently measured each structural
lesion (e.g. modic change, intervertebral disc and paraspinal
muscle fat content), blinded to the results of other readers.
Degenerative intervertebral disc assessment
Intervertebral disc degeneration was assessed from
T2-weighted sagittal images based on the Pfirrmann
method [11] (Table 1). Grades 4 and 5 formed a “se-
vere disc degeneration”group. The measurement was
performed by one assessor who was trained to meas-
ure disc degeneration by a radiologist experienced in
musculoskeletal MRI, blinded to the characteristics of
the participants. Images were reassessed 1 week apart.
The intra-rater reliability of the disc degeneration
measures at each vertebral level was high, with intra-
class correlation coefficients (ICCs) ranging from 0.88
to 0.94 for the I-V grading system.
Modic change
Modic change was classified according to the original
system [21, 27] into 3 types:
Type 1: hypointense on T1 and hyperintense on T2
images
Table 1 Pfirrmann grading of lumbosacral disc degeneration
a
Grade Structure Distinction
of nucleus and
annulus
Signal intensity Height of
intervertebral
disc
I Homogenous,
bright white
Clear Hyperintense,
isointense to
cerebrospinal
fluid
Normal
II Inhomogenous
with or without
horizontal
bands
Clear Hyperintense,
isointense to
cerebrospinal
fluid
Normal
III Inhomogenous,
grey
Unclear Intermediate Normal to
slightly
decreased
IV Inhomogenous,
grey to black
Lost Intermediate to
hypointense
Normal to
moderately
decreased
V Inhomogenous,
black
Lost Hypointense Collapsed
disc space
a
Adapted from Pfirrmann et al. [11], whereby grades IV and V represent
“severe intervertebral disc degeneration”
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439 Page 2 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Type 2: hyperintense on T1 and isointense/
hyperintense on T2 images
Type 3: hypointense on both T1 and T2 images
Images were assessed in the sagittal plane. A predefined
cut-off point for size was not used. The presence of modic
change was defined based on signal changes on either side
of the disc. Sixty randomly selected images were reas-
sessed for Modic change by the same observer 1 week
later. The ICC was found to be 0.74.
Paraspinal muscle fat content
Hyperintense regions of the paraspinal muscles observed
on T2 axial images at the level of each lumbar interver-
tebral disc (L1/2, L2/3, L3/4 and L4/5) were considered
to represent fat replacement [9] and categorised based
on a previously validated grading method; grade 0: no
fat, grade 1: 1–10 % fat, grade 2: 11–50 % fat and grade
3: >50 % fat [9]. High fat content was defined as greater
than 50 % of the muscle. The intra-observer ICC for the
paraspinal muscle fat content for both multifidus and
erector spinae was 0.99. To provide a measure of high
paraspinal muscle fat content in the lumbar spine, a di-
chotomous outcome was created. This measure scored
participants demonstrating >50 % of a muscle in at least
four spinal levels on either the right and/or left sides
(with the total possible score being 8).
Anthropometric data
Height was measured to the nearest 0.1 cm using a sta-
diometer. Weight was measured to the nearest 0.1 kg
using a single pair of electronic scales. BMI (kg m
−2
)
was calculated.
Chronic pain and disability
The Chronic Pain Grade Questionnaire was administered
at the time of MRI in 2011–2012 to obtain information on
low back pain intensity over the past 6 months. The
Chronic Pain Grade Questionnaire is a reliable and valid in-
strument for use in population surveys of low back pain
[28, 29]. The questionnaire includes seven questions from
which a pain intensity and disability subscale score are cal-
culated. Subscale scores for pain intensity and disability are
combined to calculate a chronic pain grade that enables
classification of chronic pain into 5 hierarchical categories:
grades 0 (no pain) to 4 (high disability, severely limiting) as
previously described [28, 29]. High intensity pain/disability
was defined as being of either grade 2 (low disability but
high intensity), grade 3 (high disability, moderately limiting)
or grade 4 (high disability, severely limiting).
Statistical analyses
Binary logistic regression was used to examine the rela-
tionships between all exposures (Modic change and fat
content of paraspinal muscles) and the prevalence of se-
vere intervertebral disc degeneration, adjusted for age,
gender, BMI and high intensity pain and or disability. A
p-value of less than 0.05 (two-tailed) was regarded as
statistically significant. All analyses were performed
using the SPSS statistical package (standard version 20.0
SPSS, Chicago, IL, USA). With 72 subjects, our study
had 80 % power to detect an odds ratio as low as 2.8,
assuming the prevalence of severe intervertebral disc de-
generation being 20 %, α= 0.05, and 2-sided significance.
Results
The characteristics of the 72 participants are shown in
Table 2. The mean (± standard deviation) age of the
Table 2 Subject demographics (n= 72)
a
Age (years) 48.7 (8.3)
Gender (n, % female) 49 (68.1)
BMI (kgm
−2
) 29.2 (7.9)
Chronic low back pain grade, n (%)
0–Pain free 14 (19.2)
1–Low disability, low intensity 44 (60.3)
2–Low disability, high intensity 5 (6.8)
3–High disability, moderately limiting 5 (6.8)
4–High disability, severely limiting 5 (6.8)
High intensity pain and or disability, n (%) 15 (20.5)
Severe intervertebral disc degeneration n (%)
L1/2 3 (4.2)
L2/3 8 (11.1)
L3/4 11 (15.3)
L4/5 23 (31.9)
L5/S1 22 (30.6)
Modic (type 2) change in vertebrae adjacent to disc n (%)
L1/L2 4 (5.6)
L2/L3 8 (11.1)
L3/L4 16 (22.2)
L4/L5 21 (29.2)
L5/S1 17 (23.6)
Fat content (>50 %) at number of lumbar spinal levels, n (%)
Multifidus Erector spinae
0 42 (57.7) 35 (47.9)
1 8 (11.3) 23 (32.4)
2 12 (16.9) 3 (4.2)
3 4 (5.6) 5 (7.0)
4 6 (8.5) 6 (8.5)
High paraspinal muscle fat content, n (%)
b
16 (22.5)
a
Results presented as mean (standard deviation) unless otherwise stated
b
Derived from participants as having >50 % of a muscle (multifidus or erector
spinae) replaced by fat in ≥4 lumbar spinal levels, with the total possible score
being 8
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439 Page 3 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

cohort was 48.7 ± 8.3 years, comprising 49 (68.1 %) fe-
males. The prevalence of severe intervertebral disc de-
generation was low at L1/2 (4.2 %) but increased at
more inferior lumbosacral levels (L2/3 11.1 %, L3/4
15.3 %, L4/5 31.9 %, L5/S1 30.6 %). Similarly, the preva-
lence of Modic type 2 change was low at the L1/2 verte-
bral level (5.6 %) but increased at more inferior
lumbosacral levels (L2/3 11.1 %, L3/4 22.2 %, L4/5
29.2 %, L5/S1 23.6 %). No participants demonstrated a
Modic type 3 change. The prevalence of Modic type 1
change was low (n= 4), and was therefore not the focus
of subsequent analyses. Sixteen participants (22.5 %) had
>50 % fat content of either or both multifidus and
erector spinae at 4 or more lumbar levels (L1/2, L2/3,
L3/4 or L4/5).
The associations between severe intervertebral disc de-
generation and Modic change in the adjacent vertebrae
are shown in Table 3. In univariate analyses, Modic
change in the L2/3 and L3/4 vertebrae was significantly
associated with accompanying severe intervertebral disc
degeneration (all p≤0.05) and approached statistical sig-
nificance at the L4/5 level (p= 0.07). After adjusting for
age, gender, BMI and high pain and or disability, these
relationships were significant or approached statistical
significance at L2/3 (OR 25.3, 95 % CI 1.4 to 471.9, p=
0.03), L3/4 (OR 4.5, 95 % CI 1.0 to 21.0, p= 0.06) and
L4/5 (OR 3.5, 95 % CI 1.0 to 12.5, p= 0.05). There was
no association between Modic change at the L5/S1 level
and severe disc degeneration at that corresponding level
(OR 1.2, 95 % CI 0.3, 3.9, p= 0.82).
The associations between high fat content of para-
spinal muscles and severe intervertebral disc degener-
ation are shown in Table 4. High fat content of the
paraspinal muscles were associated with severe degen-
erative disease at L2/3 (OR 9.9, 95 % CI 1.2 to 81.5, p=
0.03), L3/4 (OR 14.3, 95 % CI 2.2 to 91.2, p= 0.005), L5/
S1 (OR 4.5, 95 % CI 1.1 to 18.8, p= 0.04) with results ap-
proaching statistical significance at L4/5 (OR 3.7, 95 %
CI 0.8 to 16.0, p= 0.09) after adjusting for age, gender,
BMI and high pain and or disability.
Discussion
This cross-sectional study has demonstrated that severe
disc degeneration of the lumbar spine is accompanied by
other structural lesions. In particular, the presence of se-
vere disc degeneration was associated with adjacent
Modic type 2 change and high fat content of the para-
spinal muscles. These data highlight that akin to degen-
erative processes such as knee osteoarthritis, spinal
degeneration appears to be a ‘whole-organ’disease, af-
fecting cartilage (intervertebral disc), bone (Modic
change) and soft tissues (paraspinal musculature).
As in a previous study [30], we found that the greatest
burden of degenerative disc disease was in the low lum-
bar (L4/5) and lumbosacral (L5/S1) spine. Degenerative
disc disease was uncommon at L1/2, with numbers too
small to meaningfully analyse (4.2 %). Since disc degen-
eration and Modic changes are more common in the
low lumbar spine, a previous study focused on the L5/S1
region in 228 male workers [31]. Consistent with the
previous study, we did not observe a significant associ-
ation between Modic change and the risk of severe L5/
S1 degenerative disc disease. Since L5/S1 is a transitional
point in the spine, it may be that the association be-
tween Modic change and degenerative disc disease at
this level differs from the rest of the lumbar spine. In-
deed, we have demonstrated that Modic type 2 change
was associated with severe disc degeneration at most
other lumbar levels. In another previous study of 108
surgical patients with lumbar degenerative disc disease
graded by the Pfirrmann system, Modic changes corre-
lated with the grade of disc degeneration [32]. However
in this previous study, it was unclear whether Modic
change was accompanied by degenerative disc disease at
the same vertebral level. To our knowledge, the current
study is the first study to present such data. Although
this may infer a local interaction between the two struc-
tural abnormalities, the mechanism accounting for the
co-existence of degenerative disc disease and accom-
panying Modic type 2 change is unclear. It may be that
disc degeneration reduces the shock absorbing capability
of the vertebrae, resulting in Modic change. Alterna-
tively, it may be that disruption to the vertebral end-
plates, such as Modic changes, impedes nutritional
Table 3 The prevalence of severe intervertebral disc
degeneration in relation to Modic change in the adjacent
vertebrae
Disc level Prevalence of severe intervertebral disc degeneration
Univariate
OR (95 % CI)
P Multivariate
a
OR (95 % CI)
P
L2/3 7.1 (1.3, 38.7) 0.02 25.3 (1.4, 471.9) 0.03
L3/4 3.8 (1.0, 14.7) 0.05 4.5 (1.0, 21.0) 0.05
L4/5 2.7 (0.9, 7.7) 0.07 3.5 (1.0, 12.5) 0.05
L5/S1 1.3 (0.4, 4.2) 0.63 1.2 (0.3, 3.9) 0.82
a
Adjusted for age, gender, BMI and high intensity pain and or disability
Table 4 The prevalence of severe intervertebral disc
degeneration in relation to high fat content in paraspinal
muscles
Univariate
OR (95 % CI)
P Multivariate
OR (95 % CI)
P
L2/3 15.9 (2.8, 90.3) 0.002 9.9 (1.2, 81.5) 0.03
L3/4 17.3 (3.8, 79.4) <0.001 14.3 (2.2, 91.2) 0.005
L4/5 5.4 (1.6, 17.7) 0.005 3.7 (0.8, 16.0) 0.09
L5/S1 6.0 (1.8, 19.8) 0.003 4.5 (1.1, 18.8) 0.04
Adjusted for age, gender, BMI, and high intensity pain and or disability
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439 Page 4 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

support of the intervertebral disc, causing subsequent
disc degeneration. In a previous study, endplate cartilage
damage increased with age and produced considerable
changes in diffusion [33]. Longitudinal studies are re-
quired to determine which structural features may be
the antecedent event in the natural history of degenera-
tive disc disease.
In the current study, we have demonstrated that a high
fat content of paraspinal muscles is associated with se-
vere intervertebral disc degeneration at each interverte-
bral level. Muscle atrophy is, in part, characterised by fat
infiltration [22, 24]. Histological studies have demon-
strated concordance between intermuscular adipose tis-
sue detected by MRI and intra-operative specimens of
paraspinal muscles [34], with other studies corroborating
MRI as a valid method of identifying the amount of fat
in skeletal muscle [35, 36]. Nevertheless, to our know-
ledge, only one MRI study has examined the association
between paraspinal muscle fat infiltration and interverte-
bral disc degeneration. A retrospective study of 78 par-
ticipants showed only a tendency toward multifidus
muscle atrophy (defined by the degree of fat and fibrous
tissue replacement) being associated with nerve root
compression, herniated nucleus pulposus and the num-
ber of degenerated discs [9]. The mechanism accounting
for the relationship between a high fat content of para-
spinal muscles and severe degenerative disc disease is
speculative. It is possible that degenerative disc disease
causes pain and reduced activity levels, resulting in fat
replacement of paraspinal muscles. We have however
adjusted our results for people with high intensity pain
and or disability, suggesting that the observed associa-
tions are independent of the potential confounding effect
of varied physical activity levels. Equally plausible is the
potential for fatty replacement of paraspinal muscles to
reduce segmental stability of the spine, causing disc de-
generation. Longitudinal studies will help to address
such issues.
A limitation of this study was its cross-sectional design,
and thus it cannot be determined whether associations be-
tween degenerative disc disease and other structural fea-
tures are a cause or result of one another. We used the
Pfirrmann grading system to assess disc degeneration.
While this 5 grade system has difficulty discriminating disc
pathology in the elderly spine (mean age 73 years; range 67
to 83 years) and requires a modified grading system [37],
our cohort was relatively young (mean age 48.7 (±8.3)
years). Additionally, we used a semi-quantitative method of
assessing fat replacement of paraspinal muscle based on
previously employed methods [9, 22, 38] and further
adapted this system whereby a high fat content within the
paraspinal compartment necessitated a participant demon-
strating >50 % of a muscle in at least four spinal levels in
any combination of the right and left sides (with the total
possible score being 8). We combined the erector spinae
and multifidus muscles into the posterior compartment in
an attempt to identify individuals with poor quality sup-
porting musculature, rather than a focus on individual mus-
cles. This is a conservative approach and any potential
misclassification of high paraspinal fat content is likely to
have reduced our ability to demonstrate statistically signifi-
cant associations. Similarly, any potential misclassification
of disc degeneration in this study, whereby grades 4 and 5
represented severe disease, is likely to be non-differential
and have underestimated any of the associations observed
in this study. Moreover, although we have asserted that our
MRI measure captured replacement of muscle with fat
based on the concordance between intermuscular adipose
tissue detected by MRI and intra-operative specimens of
paraspinal muscles [34], it is possible that other fibrous
non-muscular elements may have been captured by this
assessment. Furthermore, this study recruited community-
based subjects. The presence of chronic pain was not re-
quired for inclusion in this study, which likely accounts for
thepredominanceoftype2,ratherthantype1Modic
change. Moreover, inclusion criteria necessitating the need
for chronic pain can be problematic, since avoidance behav-
iours and psychosocial variability are likely to be apparent
in chronic diseases [39, 40]. For instance, it has been docu-
mented that fear of movement is a common occurrence
among people with chronic low back pain [41], and selec-
tion of such subgroups in study designs may lead to selec-
tion bias. Instead, we chose to measure community-based
subjects with the aim of capturing a spectrum of spinal ab-
normalities. Nevertheless, we have adjusted our analyses for
the presence of high pain and or disability.
Conclusion
This study has demonstrated that severe disc degener-
ation of the lumbar spine is accompanied by other struc-
tural lesions. In particular, the presence of severe disc
degeneration is associated with adjacent Modic type 2
change and high fat content of the paraspinal muscles.
Although longitudinal studies are required to determine
the temporal relationship between these changes, these
data highlight the ‘whole-organ’disease occurring in disc
degeneration. Understanding this will have the potential
to identify novel targets for the treatment and preven-
tion of lumbosacral disc degeneration.
Abbreviations
BMI: Body mass index; CI: Confidence interval; ICC: Intra-class correlation
coefficient; IL: Interleukin; MRI: Magnetic resonance imaging; OR: Odds ratio;
TNF: Tumour necrosis factor
Funding
The work was funded by the Monash University Strategic Grant Scheme
(PAG001). A.J.T is the recipient of the NHMRC Early Career Fellowship
(#1073284). D.M.U, Y.W and A.E.W are the recipients of NHMRC Career
Development Fellowships (Clinical level 1 #1011975, Clinical level 1 #1065464
and Clinical Level 2 #1063574, respectively).
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439 Page 5 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Availability of data and materials
Data will be shared if formal consultation is sought, and approved by
Professor Flavia Cicuttini (flavia.cicuttini@monash.edu).
Authors’contributions
AJT contributed to study design, data acquisition, data analyses, manuscript
preparation, DU contributed to funding, initial recruitment, study design,
data acquisition, manuscript preparation, YW contributed to data acquisition,
data analyses, manuscript preparation, AEW contributed to funding, initial
recruitment, study design, data analyses, manuscript preparation, RO
contributed to data acquisition, manuscript preparation, GJ contributed to
funding, initial recruitment, data acquisition, manuscript preparation FC
contributed to funding, initial recruitment, study design, data acquisition,
data analyses, manuscript preparation. All authors read and approved the
final version.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
The study was approved by the Human Research Ethics Committees of the
Alfred Hospital and Monash University. Participants provided their informed
consent to participate in the study.
Author details
1
Department of Epidemiology and Preventive Medicine, School of Public
Health and Preventive Medicine, Monash University, Alfred Hospital,
Melbourne, VIC 3004, Australia.
2
Baker IDI Heart and Diabetes Institute,
Commercial Road, Melbourne, VIC 3004, Australia.
3
Healthcare Imaging
Services, Epworth Hospital, Richmond, Melbourne, VIC 3121, Australia.
4
Department of Medicine, Central Clinical School, Monash University,
Melbourne, VIC 3004, Australia.
5
Menzies Research Institute, Private bag 23,
Hobart, TAS 7000, Australia.
Received: 21 January 2016 Accepted: 13 October 2016
References
1. Powell MC, Wilson M, Szypryt P, Symonds EM, Worthington BS. Prevalence
of lumbar disc degeneration observed by magnetic resonance in
symptomless women. Lancet. 1986;2(8520):1366–7.
2. Hicks GE, Morone N, Weiner DK. Degenerative lumbar disc and facet disease
in older adults: prevalence and clinical correlates. Spine (Phila Pa 1976).
2009;34(12):1301–6. doi:10.1097/BRS.0b013e3181a18263.
3. Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A.
Low back pain in relation to lumbar disc degeneration. Spine. 2000;25(4):487–92.
4. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG.
Classification of age-related changes in lumbar intervertebral discs: 2002
Volvo Award in basic science. Spine (Phila Pa 1976). 2002;27(23):2631–44.
5. Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB.
Preliminary evaluation of a scheme for grading the gross morphology of
the human intervertebral disc. Spine (Phila Pa 1976). 1990;15(5):411–5.
6. Mimura M, Panjabi MM, Oxland TR, Crisco JJ, Yamamoto I, Vasavada A. Disc
degeneration affects the multidirectional flexibility of the lumbar spine.
Spine (Phila Pa 1976). 1994;19(12):1371–80.
7. Lane NE, Nevitt MC, Genant HK, Hochberg MC. Reliability of new indices of
radiographic osteoarthritis of the hand and hip and lumbar disc
degeneration. J Rheumatol. 1993;20(11):1911–8.
8. Yu S, Haughton VM, Sether LA, Ho KC, Wagner M. Criteria for classifying normal
and degenerated lumbar intervertebral disks. Radiology. 1989;170(2):523–6.
9. Kader DF, Wardlaw D, Smith FW. Correlation between the MRI changes in
the lumbar multifidus muscles and leg pain. Clin Radiol. 2000;55(2):145–9.
10. Urquhart DM, Kurniadi I, Triangto K, Wang Y, Wluka AE, O’Sullivan R, Jones
G, Cicuttini FM. Obesity is Associated With Reduced Disc Height in the
Lumbar Spine but not at the Lumbosacral Junction. Spine. 2014;12:12.
11. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance
classification of lumbar intervertebral disc degeneration. Spine (Phila Pa
1976). 2001;26(17):1873–8.
12. Kettler A, Wilke HJ. Review of existing grading systems for cervical or
lumbar disc and facet joint degeneration. Eur Spine J. 2006;15(6):705–18.
Epub 2005 Sep 20.
13. Teichtahl AJ, Wluka AE, Davies-Tuck ML, Cicuttini FM. Imaging of knee
osteoarthritis. Best Pract Res Clin Rheumatol. 2008;22(6):1061–74.
14. Toyone T, Takahashi K, Kitahara H, Yamagata M, Murakami M, Moriya H.
Vertebral bone-marrow changes in degenerative lumbar disc disease. An
MRI study of 74 patients with low back pain. J Bone Joint Surg (Br).
1994;76(5):757–64.
15. Mitra D, Cassar-Pullicino VN, McCall IW. Longitudinal study of vertebral type-
1 end-plate changes on MR of the lumbar spine. Eur Radiol. 2004;14(9):
1574–81. Epub 2004 Apr 2.
16. Kuisma M, Karppinen J, Niinimaki J, Ojala R, Haapea M, Heliovaara M,
Korpelainen R, Taimela S, Natri A, Tervonen O. Modic changes in endplates
of lumbar vertebral bodies: prevalence and association with low back and
sciatic pain among middle-aged male workers. Spine (Phila Pa 1976). 2007;
32(10):1116–22.
17. Albert HB, Manniche C. Modic changes following lumbar disc herniation.
Eur Spine J. 2007;16(7):977–82. Epub 2007 Mar 3.
18. Modic MT. Modic type 1 and type 2 changes. J Neurosurg Spine. 2007;6(2):
150–1. discussion 1.
19. Weishaupt D, Zanetti M, Hodler J, Boos N. MR imaging of the lumbar spine:
prevalence of intervertebral disk extrusion and sequestration, nerve root
compression, end plate abnormalities, and osteoarthritis of the facet joints
in asymptomatic volunteers. Radiology. 1998;209(3):661–6.
20. Kjaer P, Korsholm L, Bendix T, Sorensen JS, Leboeuf-Yde C. Modic changes
and their associations with clinical findings. Eur Spine J. 2006;15(9):1312–9.
Epub 2006 Aug 9.
21. Modic MT, Masaryk TJ, Ross JS, Carter JR. Imaging of degenerative disk
disease. Radiology. 1988;168(1):177–86.
22. Kjaer P, Bendix T, Sorensen JS, Korsholm L, Leboeuf-Yde C. Are MRI-defined
fat infiltrations in the multifidus muscles associated with low back pain?
BMC Med. 2007;5:2.
23. Fischer MA, Nanz D, Shimakawa A, Schirmer T, Guggenberger R, Chhabra A,
Carrino JA, Andreisek G. Quantification of muscle fat in patients with low
back pain: comparison of multi-echo MR imaging with single-voxel MR
spectroscopy. Radiology. 2013;266(2):555–63. doi:10.1148/radiol.12120399.
Epub 2012 Nov 9.
24. Mengiardi B, Schmid MR, Boos N, Pfirrmann CW, Brunner F, Elfering A,
Hodler J. Fat content of lumbar paraspinal muscles in patients with chronic
low back pain and in asymptomatic volunteers: quantification with MR
spectroscopy. Radiology. 2006;240(3):786–92.
25. Teichtahl AJ, Urquhart DM, Wang Y, Wluka AE, O’Sullivan R, Jones G,
Cicuttini FM. Physical inactivity is associated with narrower lumbar
intervertebral discs, high fat content of paraspinal muscles and low back
pain and disability. Arthritis Res Ther. 2015;17(1):114.
26. Teichtahl AJ, Urquhart DM, Wang Y, Wluka AE, Wijethilake P, O’Sullivan R,
Cicuttini FM. Fat infiltration of paraspinal muscles is associated with low
back pain, disability, and structural abnormalities in community-based
adults. Spine J. 2015;28(15):00326–5.
27. Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk
disease: assessment of changes in vertebral body marrow with MR imaging.
Radiology. 1988;166(1 Pt 1):193–9.
28. Von Korff M, Ormel J, Keefe FJ, Dworkin SF. Grading the severity of chronic
pain. Pain. 1992;50(2):133–49.
29. Smith BH, Penny KI, Purves AM, Munro C, Wilson B, Grimshaw J, Chambers
WA, Smith WC. The Chronic Pain Grade questionnaire: validation and
reliability in postal research. Pain. 1997;71(2):141–7.
30. West W, West KP, Younger EN, Cornwall D. Degenerative disc disease of the
lumbar spine on MRI. West Indian Med J. 2010;59(2):192–5.
31. Kuisma M, Karppinen J, Haapea M, Niinimaki J, Ojala R, Heliovaara M,
Korpelainen R, Kaikkonen K, Taimela S, Natri A, Tervonen O. Are the
determinants of vertebral endplate changes and severe disc degeneration
in the lumbar spine the same? A magnetic resonance imaging study in
middle-aged male workers. BMC Musculoskelet Disord. 2008;9:51. doi:10.
1186/471-2474-9-51.
32. Yu LP, Qian WW, Yin GY, Ren YX, Hu ZY. MRI assessment of lumbar
intervertebral disc degeneration with lumbar degenerative disease using
the Pfirrmann grading systems. PLoS One. 2012;7(12):e48074.
33. Rajasekaran S, Babu JN, Arun R, Armstrong BR, Shetty AP, Murugan S. ISSLS prize
winner: A study of diffusion in human lumbar discs: a serial magnetic resonance
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439 Page 6 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

imaging study documenting the influence of the endplate on diffusion in
normal and degenerate discs. Spine (Phila Pa 1976). 2004;29(23):2654–67.
34. Rossi A, Zoico E, Goodpaster BH, Sepe A, Di Francesco V, Fantin F, Pizzini F,
Corzato F, Vitali A, Micciolo R, Harris TB, Cinti S, Zamboni M. Quantification of
intermuscular adipose tissue in the erector spinae muscle by MRI: agreement
with histological evaluation. Obesity (Silver Spring). 2010;18(12):2379–84.
35. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross
R. Cadaver validation of skeletal muscle measurement by magnetic
resonance imaging and computerized tomography. J Appl Physiol (1985).
1998;85(1):115–22.
36. Phoenix J, Betal D, Roberts N, Helliwell TR, Edwards RH. Objective
quantification of muscle and fat in human dystrophic muscle by magnetic
resonance image analysis. Muscle Nerve. 1996;19(3):302–10.
37. Griffith JF, Wang YX, Antonio GE, Choi KC, Yu A, Ahuja AT, Leung PC.
Modified Pfirrmann grading system for lumbar intervertebral disc
degeneration. Spine (Phila Pa 1976). 2007;32(24):E708–12.
38. Parkkola R, Rytokoski U, Kormano M. Magnetic resonance imaging of the
discs and trunk muscles in patients with chronic low back pain and healthy
control subjects. Spine (Phila Pa 1976). 1993;18(7):830–6.
39. Philips HC. Avoidance behaviour and its role in sustaining chronic pain.
Behav Res Ther. 1987;25(4):273–9.
40. Gatchel RJ, Polatin PB, Mayer TG. The dominant role of psychosocial risk
factors in the development of chronic low back pain disability. Spine (Phila
Pa 1976). 1995;20(24):2702–9.
41. Vlaeyen JW, Kole-Snijders AM, Boeren RG, van Eek H. Fear of movement/
(re)injury in chronic low back pain and its relation to behavioral
performance. Pain. 1995;62(3):363–72.
• We accept pre-submission inquiries
• Our selector tool helps you to find the most relevant journal
• We provide round the clock customer support
• Convenient online submission
• Thorough peer review
• Inclusion in PubMed and all major indexing services
• Maximum visibility for your research
Submit your manuscript at
www.biomedcentral.com/submit
Submit your next manuscript to BioMed Central
and we will help you at every step:
Teichtahl et al. BMC Musculoskeletal Disorders (2016) 17:439 Page 7 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com