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.



Inflammatory and Catabolic Signalling in Intervertebral Discs: The Roles of NF-KB and MAP KinasesKarin Wuertz, Nam Vo, Dimitris Kletsas and Norbert Boos


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.


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).


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).


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 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α): Le Maitre et al. (2007) demonstrated that herniated discs and degenerated discs from patients with chronic back pain showed higher expression of IL-1 β and TNF-α than non-degenerated discs derived from post-mortem tissue from people without a history of back pain. In fact, not only IL-1 β, but also IL-1α, type I receptor of IL-1 and the IL-1 β-converting enzyme were present in higher levels in degenerated samples to non-degenerated ones (Le Maitre et al., 2005).


Furthermore, TNF-α 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-α 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-α 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.


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.


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-κB 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. METHODS: 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 < -0.001). Relative risk in relatives was significantly elevated in both first-degree (relative risk, 4.15; p < 0.001) and third-degree relatives (relative risk 1.46; p < 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.


Gene Therapy for the Treatment of Degenerative Disk DiseaseMark 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.


A Population-Based Study of Juvenile Disc Degeneration and its Association with Overweight and Obesity, Low Back Pain, and Diminished Functional StatusDino 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 < 0.001), high-intensity zones on MRI (p = 0.040), and greater weight (p < 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 < 0.05) than individuals without disc degeneration. The p value of < 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.



Orientation of the Lumbar Facet Joints: Association with Degenerative Disc DiseaseS 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.


Erosive Arthritis and Spondyloarthropathy on Old World Primates Rothschild BM, Woods RJ Am J Phys Anthrolol. 1992 Jul; 88(3):389-400. Arthritis 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 Reiter’s 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/spondyloarthropathy 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.


Degenerative Disc Disease Stem Cell Treatment



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. Mary’s Hospital, The Catholic University of Korea School of Medicine, 65-1 Kumho-dong, Uijongbu-si, Kyunggi-do, Seoul 480-130, Korea. [email protected] 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.


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. Abstract 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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Degenerative Disc Disease is Arthritis of the Spine