Degenerative Disc Disease is Arthritis of the Spine

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Degenerative Disc Disease is Arthritis of the
Spine

• Stephen Fuller, MD

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Abnormal magnetic-resonance scans of the lumbar
spine in asymptomatic subjects. A prospective
investigation.   Boden SD, et al.   J Bone Joint
Surg Am. 1990 Mar 72(3)403-8.   Department of
Orthopaedic Surgery, George Washington University
Medical Center, Washington, D.C.   Abstract   We
performed magnetic resonance imaging on
sixty-seven individuals who had never had
low-back pain, sciatica, or neurogenic
claudication. The scans were interpreted
independently by three neuro-radiologist who had
no knowledge about the presence of absence of
clinical symptoms in the subjects. About
one-third of the subjects were found to have a
substantial abnormality. Of those who were less
than sixty years old, 20 per cent had a herniated
nucleus pulposus and one had spinal stenosis. In
the group that was sixty years or older, the
findings were abnormal on about 57 per cent of
the scans 36 per cent of the subjects had a
herniated nucleus pulposus and 21 per cent had
spinal stenosis. There was degeneration or
bulging of a disc at at least one lumbar level in
35 per cent of the subjects between twenty and
thirty-nine years old and in all but one of the
sixty to eighty-year-old subjects. In view of
these findings in asymptomatic subjects, we
concluded that abnormalities on magnetic
resonance images must be strictly correlated with
age and any clinical signs and symptoms before
operative treatment is contemplated.
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Inflammatory and Catabolic Signalling in
Intervertebral Discs The Roles of NF-KB and MAP
Kinases Karin Wuertz, Nam Vo, Dimitris Kletsas
and Norbert Boos
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Introduction   Degeneration of the intervertebral
disc (IVD) is a normal part of the ageing
process, and is typically characterised by a loss
of the disc extracellular matrix. This loss is
due to perturbed matrix homeostasis, whereby
matrix anabolism is decreased and matrix
catabolism is increased. Aging is associated
with increased cellular senescence and changes in
disc cellular phenotype that result in cells with
decreased matrix synthesis capacity and/or
altered matrix production. Additionally, enzymes
mediating matrix degradation, including matrix
metalloproteinases (MMPs), are up-regulated
during the process of IVD degeneration and aging,
resulting in increased matrix degradation (Cui et
al., 2010 Roberts et al., 2000 Weiler et al.,
2002). Consequently, loss and remodelling of the
extracellular matrix (ECM) can lead to the
occurrence of clefts and tears and eventually
complete disc structural failure.
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Despite the large structural changes in their
discs, patients with IVD degeneration often
remain symptom-free. Nevertheless, a subgroup of
individuals with IVD degeneration experience pain
and thus can be categorised to have
intervertebral disc disease (IDD). A recent
systematic review indicated that the odds of
chronic low back pain given the presence of disc
degeneration (detected by magnetic resonance
imaging changes) ranged from 1.8 to 2.8, meaning
that the chances of suffering from back pain in
people with degenerated discs was 2-3 times
higher than in individuals without degenerated
discs (Chou et al., 2011).
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Important in the context of disc-related back
pain is the observed phenomenon of innervation of
sensory nerve fibres in degenerated discs. These
sensory nerves, containing nociception-related
mediators such as substance P or calcitonin can
penetrate not only into the peripheral annulus
fibrosus (AF), but also into deeper zones of
degenerated discs, especially if radial fissures
and reduced pressure in the nucleus pulposus are
present, (Adams et al., 1996 Freemont et al.,
1997 Hastreiter et al., Osawa et al., 2006 Peng
et al., 2005). Irritation of these sensory
nerves has been described as a major underlying
mechanism of discogenic back pain, which may
occur via inflammatory processes (Goupille et
al., 2007 Olmarker and Rydevik, 1998).
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Recently, surgically-removed human degenerative
discs were shown to be actively inflammatory
(Adams et al., 2010). Past research has also
provided evidence that IDD is correlated to
i8ncreased levels of pro-inflammatory cytokines
in disc tissue, such as interleukin 1ß (IL-1ß),
interleukin 6 (IL-6), interleukin 8 (IL-8) and
tumor necrosis factor a (TNF-a) Le Maitre et
al. (2007) demonstrated that herniated discs and
degenerated discs from patients with chronic back
pain showed higher expression of IL-1 ß and TNF-a
than non-degenerated discs derived from
post-mortem tissue from people without a history
of back pain. In fact, not only IL-1 ß, but also
IL-1a, type I receptor of IL-1 and the IL-1
ß-converting enzyme were present in higher levels
in degenerated samples to non-degenerated ones
(Le Maitre et al., 2005).
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Furthermore, TNF-a expression increased
continuously with age in the AF and up to the age
of 60 years in the nucleus pulposus (NP) in a
population study consisting of autopsy samples
that did not have any medical notes concerning
relevant back problems (Bachmeier et al., 2007).
Importantly, surgical samples from patients with
low back pain history (protrusion, herniation,
degenerative disc disease) showed higher level of
TNF-a positively labelled cells than the autopsy
group (Bachmeier et al., 2007). Similarly,
Weiler et al. (2005) demonstrated that surgical
disc tissue from symptomatic back pain patients
contained more TNF-a positive cells than
asymptomatic autopsy samples, with a positive
correlation to the degree of degeneration for the
AF. Burke et al. (2002) clearly demonstrated
that disc tissue from patients with discogenic
back pain revealed higher protein levels of IL-6
and IL-8 than patients with sciatica.
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A most recent immunohistochemical comparison of
surgical disc tissue (degenerative disc disease,
disc herniation) and non-degenerated autopsy
discs showed higher expression of IL-4, IL-6, and
IL-12 in surgical samples than in autopsy
samples, but with highest levels in the cases of
disc herniation (Shamji et al., 2010). In
summary, these studies indicate that the
inflammatory mediators play an important role in
the processes of IDD and possibly IDD-related
back pain.
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During the past years, gene expression and
function of these mediators in IDD have been a
major topic of research interest. Furthermore,
extensive therapeutic studies in the field of
osteoarthritis and rheumatoid arthritis have
highlighted the need to identify the underlying
signalling pathways, prompting scores of IVD
researchers to explore the molecular mechanisms
leading to IVD inflammation and catabolism. This
review describes two major intracellular
pathways, nuclear factor kappa B (NF-?B and MAP
kinase pathways (as described in this review
paper) is given in Fig. 1.
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Evidence for an Inherited Predisposition to
Lumbar Disc Disease (JBJS(A)) Alpesh A Patel
William Ryan Spiker Michael Daubs Darrel
Brodke Lisa A Cannon-Albright   BACKGROUND A
genetic predisposition for the development of
symptomatic lumbar disc disease has been
suggested by several twin sibling studies and
subsequent genetic marker studies. The purpose
of the present study was to define
population-based familial clustering among
individuals with a diagnosis of, or treated for,
lumbar disc herniation or disc degeneration.   MET
HODS The Utah Population Database allows
analysis of combined health and genealogic data
over one million Utah residents. We used the
International Classification of Diseases, Ninth
Revision, diagnosis codes entered in patient
records to identify patients with a diagnosis of
either lumbar disc herniation or lumbar disc
degeneration and genealogic data. The hypothesis
of excess relatedness (familial clustering) was
tested with use of the Genealogical Index of
Familiality, which compares the average
relatedness of affected individuals with expected
population relatedness. Relative risks in
relatives were estimated by comparing rates of
disease in relatives with expected population
rates (estimated from the relatives of matched
controls). This methodology has been previously
reported for other disease conditions but not for
spinal diseases.   RESULTS The Genealogical
Index of Familiality test for 1264 patients with
lumbar disc disease showed a significant excess
relatedness (p lt -0.001). Relative risk in
relatives was significantly elevated in both
first-degree (relative risk, 4.15 p lt 0.001) and
third-degree relatives (relative risk 1.46 p lt
0.027).   CONCLUSIONS Excess relatedness of
affected individuals and elevated risks to both
near and distant relatives was observed, strongly
supporting a heritable contribution to the
development of symptomatic lumbar disc disease.
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Gene Therapy for the Treatment of Degenerative
Disk Disease Mark G Hubert Gianluca Vadala
Gwendolyn Sowa Rebecca K Studer James D
Kang   Recent biologic and biochemical advances
have furthered our understanding of the complex
environment of the intervertebral disk. This new
understanding has allowed researchers to pursue
novel treatments of intervertebral disk
degeneration, targeting the biochemical pathways
involved in the degenerative cascade. Gene
therapy has shown much promise in this regard.
Many new targets for gene therapy in the
intervertebral disk have been identified, such as
TGF-beta1, TIMP-1, and LMP-1. In addition, new
vectors such as the adeno-associated virus, are
being investigated for use in intervertebral disk
applications. Cell-based therapy has also shown
significant promise in the biologic treatment of
intervertebral disk degeneration. With continued
efforts, gene therapy may prove to be an
extremely powerful took in the treatment of
intervertebral disk degeneration.  
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A Population-Based Study of Juvenile Disc
Degeneration and its Association with Overweight
and Obesity, Low Back Pain, and Diminished
Functional Status Dino Samartzis Jaro Karppinen
Florence Mok Daniel Y T Fong Keith D K Luk
Kenneth M C Cheung   BACKGROUND Little is known
regarding juvenile disc degeneration in
individuals with normal spinal alignment.
Consequently, the purpose of this study was to
assess the prevalence, determinants, and clinical
relevance associated with juvenile disc
degeneration of the lumbar spine in individuals
without spinal deformities.   METHODS A
cross-sectional assessment of disc degeneration
in juveniles was performed as part of a
population-based study of 1989 Southern Chinese
volunteers. Adolescents and young adults from
thirteen to twenty years of age were defined as
juveniles. Juvenile subjects with no spinal
deformity (n 83) were stratified into two
groups, those with and those without juvenile
disc degeneration. Sagittal T2-weighed magnetic
resonance images (MRI) were evaluated for the
presence and extent of disc degeneration as well
as other spinal findings. Demographics were
assessed and clinical profiles were collected
with use of standardized questionnaires.   RESULTS
Juvenile disc degeneration was present in 35
(twenty-nine) of the juveniles without spinal
deformity. Disc bulging or extrusion (p lt
0.001), high-intensity zones on MRI (p 0.040),
and greater weight (p lt 0.001) and height (p
0.002) were significantly more prevalent in
subjects with juvenile disc degeneration.
Adjusted multivariate logistic regression
modeling demonstrated that Asian-modified
body-mass index (BMI) values in the overweight or
obese range had a significant association with
juvenile disc degeneration (odds ratio 14.19
95 confidence interval 1.44 to 140.40 p
0.023). Overweight and obese individuals had
greater severity of disc degeneration than
underweight and normal-weight individuals (p
0.036). Furthermore, individuals with juvenile
disc degeneration had an increased prevalence of
low back pain and/or sciatica (p 0.049), and
greater physical disability (p lt 0.05) than
individuals without disc degeneration. The p
value of lt 0.05 for physical disability
represents both the physical function (p 0.006)
and the physical component (p 0.032) of the
SF-36.   CONCLUSIONS This study demonstrated
that the presence of juvenile disc degeneration
was strongly associated with overweight and
obesity, low back pain, increased low back pain
intensity, and diminished physical and social
functioning. Furthermore, an elevated BMI was
significantly associated with increased severity
of disc degeneration. This study has public
health implications regarding overweight and
obesity and the development of lumbar disc
disease.
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Orientation of the Lumbar Facet Joints
Association with Degenerative Disc Disease S D
Boden K D Riew K Yamaguchi T P Branch D
Schellinger S W Wiesel   The orientation of the
lumbar facet joints was studied with magnetic
resonance imaging in 140 subjects to determine if
there is an association between facet tropism and
intervertebral disc disease or between the
orientation of the facet joints and degenerative
spondylolisthesis. The 140 subjects were divided
into four groups sixty-seven asymptomatic
volunteers, forty-six of whom did not have a
herniated disc on magnetic resonance scans (Group
I) and twenty-one who did (Group II) forty-six
symptomatic patients who had a herniated disc
confirmed operatively (Group III) and
twenty-seven patients who had degenerative
spondylolisthesis at the interspace between the
fourth and fifth lumbar vertebrae (Group IV).
Axial scans were made at each lumbar level and
digitized, and the facet joint angle was measured
by two independent observers with use of image
analysis software in a personal computer. The
technique of measurement of the facet angles on
magnetic resonance scans was validated with a
subset of subjects who also had computed
tomography scans made. Similar values were
obtained with the two methods (r 0.92 p
0.00001). For the forty-six asymptomatic
volunteers who did not have a herniated disc on
the magnetic resonance scans (Group I), the
median facet tropism was 5 to 6 degrees and was
more than 10 degrees in 24 per cent (eleven) of
the subjects. There was no association between
increased facet tropism and disc degeneration.
At the level of the fourth and fifth lumbar
vertebrae, the median facet tropism was 10.3
degrees in the symptomatic patients who had a
herniated disc at the same level and 5.4 degrees
in the asymptomatic volunteers (Group 1) (p
0.05). The mean orientation of the lumbar facet
angles relative to the coronal plane was more
sagittal at all levels in the patients who had
degenerative spodylolisthesis. The greatest
difference was at the level of the fourth and
fifth lumbar vertebrae (p 0.000001). The mean
facet angle was 41 degrees (95 per cent
confidence interval, 37/6 to 44.6 degrees) in the
asymptomatic volunteers and 60 degrees (95 per
cent confidence interval, 52.7 to 67.1) in the
patients who had degenerative spondylosthesis. An
individual in who both facet-joint angles at the
level of the fourth and fifth vertebrae were more
than 45 degrees relative to the coronal plane was
twenty-five times more likely to have
degenerative spondylosthesis (95 per cent
confidence interval, seven to ninety-eight
times). The increase in facet angles at levels
other than that of the spodylosthesis suggests
the increased facet angles represent variations
in anatomy rather than a secondary result of
spondylosthesis.
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Erosive Arthritis and Spondyloarthropathy on Old
World Primates   Rothschild BM, Woods RJ   Am J
Phys Anthrolol. 1992 Jul 88(3)389-400.   Arthrit
is Center of Northeast Ohio, Youngstown
44512   Abstract   Presence of spine and
sacroiliac involvement and the nature of
distribution of the erosive lesions allow
definitive diagnosis of spondyloarthropathy.
Thus, Spondyloarthropathy was identified in
Theropithecus, Papio, Cercopithecus, Macaca,
Colobus, Presbytis, and Hylobates. Only
monarticular erosive disease was present in
prosimians, precluding a diagnosis of
spondyloarthropathy for that group. The
distribution of erosive disease and axial joint
involvement in 1,349 non-prosimian Old World
primates is quite characteristic of that noted in
human psoriatic arthritis. While Reiters
syndrome must also be considered, the histologic
appearance of skin lesions in Macaca is
characteristic of psoriasis. Evidence of
spondyloarthropathy abounds in the literature of
primate skeletal disease. Environmentally based
contagions may be important in the
pathophysiology of spondyloarthropathy. The wide
geographic distribution of the phenomena in
monkeys suggests a panendemic, with limited
individual susceptibility (compared to that noted
in gorillas and chimpanzees). Identical
occurrence of erosive arthritis/spondyloarthropath
y in free-ranging and artificially restrained
animals suggests that spondyloarthropathy can
validly be studied in artificially restrained
populations. This perspective should allow
application of human therapeutic approaches to
and perhaps improve the quality of life for
artificially restrained, afflicted individuals.
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Degenerative Disc Disease Stem Cell Treatment
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Mitochondrial Involvement in Fas-Mediated
Apoptosis of Human Lumbar Disc Cells   Park JB,
Lee JK, Park SJ, Kim KW, Riew KD.   J Bone Joint
Surg Am. 2005 Jun 87(6) 1338-42   Department of
Orthopaedic Surgery, Uijongbu St. Marys
Hospital, The Catholic University of Korea School
of Medicine, 65-1 Kumho-dong, Uijongbu-si,
Kyunggi-do, Seoul 480-130, Korea.
Spinepjb_at_catholic.ac.kr   Abstract   BACKGROUND
Two main pathways of Fas-mediated apoptosis have
been identified The Type-I (death-inducing
signaling complex) pathway and the Type-II
(mitochondrial pathway). While apoptotic cell
death has been implicated in lumbar degenerative
disc disease, we are not aware of any studies in
which surgically removed discs from live humans
have been examined to determine which of the two
pathways is involved in the apoptosis of disc
cells. As an initial step in the development of
therapies to inhibit inappropriate or premature
apoptosis of disc cells, our objective was to
determine which pathway is involved.   METHODS
We examined thirty-two samples of herniated
lumbar disc tissue with use of immunohistochemical
staining and Western blot analysis to determine
the presence of several proteins, including
caspase-8 (associated with the Type-I pathway)
BID (BH3 interacting domain death agonist),
cytochrome-c, and caspase-9 (associated with the
Type-II pathway) and caspase-3 (an executioner
of apoptosis). The TUNEL (terminal
deoxynucleotydl transferase TDT-mediated dUTP
nick end labeling) assay was performed to confirm
the occurrence of apoptosis of the disc
cells.   RESULTS The proteins associated with
the Type-II pathway (BID, cytochrome-c, and
caspase-9) stained positively in all samples.
Although the protein associated with the Type-I
pathway (caspase-8) was not detected on
immunohistochemical analysis, a small amount of
caspase-8 was detected on Western blot analysis.
However, the expression of Type-II proteins was
still higher than the expression of caspase-8 on
Western blot analysis. The expression of
caspase-3 was identified in all samples with
immunohistochemical and Western blot analysis.
TUNEL-positive disc cells were identified in all
samples.   CONCLUSIONS The results of the
present study suggest that human disc cells are
Type-II cells which undergo apoptic death through
mitochondrial involvement.
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Degenerative Disk Disease Assessment of Changes
in Vertebral Body Marrow with MR Imaging   M.T.
Modic P.M. Steinberg J.S. Ross T.J. Masaryk
J.R. Carter (Profiled Author Michael
Modic)   Radiology 1988 166(1 I)193-199.   Abstr
act   The authors reviewed magnetic resonance
(MR) images of 474 consecutive patients referred
for lumbar spine MR Imaging. Type 1 changes
(decreased signal intensity on T1-weighted
spin-echo images and increased signal intensity
on T-2 weighed images) were identified in 20
patients (4) and type 2 (increased signal
intensity on T2-weighted images) in 77 patients
(16). IN all cases there was evidence of
associated degenerative disk disease at the level
of involvement. Histopathologic sections in
three cases of type 1 change demonstrated
disruption and fissuring of the end plates and
vascularized fibrous tissue, while in three cases
of type 2 change they demonstrated yellow marrow
replacement. In addition, 16 patients with end
plate changes documented with MR were studied
longitudinally. Type 1 changes in five of six
patients converted to a type 2 pattern in 14
months to 3 years. Type 2 changes in ten
patients remained stable over a 2-3 year period.
These signal intensity changes appear to reflect
a spectrum of vertebral body marrow changes
associated with degenerative disk disease.
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Lumbar Degenerative Disk Disease   Michael T.
Modic Jeffrey S. Ross (Profiled Author Michael
Modic)   Radiology 2007 245(1)43-61   Abstract  
The sequelae of disk degeneration are among the
leading causes of functional incapacity in both
sexes and are a common source of chronic
disability in the working years. Disk
degeneration involves structural disruption and
cell-mediated changes in composition.
Mechanical, traumatic, nutritional, and genetic
factors all may play a role in the cascade of
disk degeneration, albeit to variable degree in
different individuals. The presence of
degenerative change is by no means an indicator
of symptoms, and there is a very high prevalence
in asymptomatic individuals. The etiology of
pain as the symptom of degenerative disease is
complex and appears to be a combination of
mechanical deformation and the presence of
inflammatory mediators. The role of imaging is
to provide accurate morphologic information and
influence therapeutic decision making. A
necessary component, which connects these two
purposes, is accurate natural history data.
Understanding the relationship of etiologic
factors, the morphologic alterations, which can
be characterized with imaging, and the mechanisms
of pain production and their interactions in the
production of symptoms will require more accurate
and reproducible stratification of patient
cohorts.
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