From: Chiropractic & Osteopathy 2006, 14:21

Cervical pillar hyperplasia is a radiological finding which first made its appearance in the literature less than 30 years ago. Its etiology and clinical significance are presently unknown; nevertheless, studies have shown that cervical pillar hyperplasia is a frequently overlooked etiology for the loss of the cervical lordosis. While these findings were disputed by several authors, other consequences of cervical pillar hyperplasia are not known at the present time. It has been theorized that the architectural difference that the presence of hyperplasia introduces into the cervical pillar may cause segmental biomechanical changes and may lead to a higher prevalence of degenerative joint disease at the hyperplastic or adjacent cervical levels. The clinical significance of this phenomenon, if found to be related to degenerative joint disease, should prompt an astute clinician into evaluating the articular pillars on all cervical spine radiographs – particularly because there could be a chance that the patient may develop degeneration at the specific cervical levels and may experience associated neck pain. The architecture of the cervical pillars cannot be modified by conservative therapy; therefore, clinicians should be aware that some of the symptoms may be attributed to degeneration and may influence the expected prognosis of the management of neck pain in those particular patients.

Currently, it is unknown whether the architecture of the articular pillars has a clinically important effect on segmental biomechanics and subsequent degeneration. The axis around which segmental flexion/extension occurs is principally influenced by the orientation of the facet joint in relation to the horizontal plane. A more horizontal facet in comparison to the plane of the superior endplate will shift the instantaneous center of rotation anteriorly, resulting in an increased load on the intervertebral disc (with changes in lateral flexion motion) and an increased risk of anterolisthesis. A straightening of the cervical curve, possibly caused by cervical pillar hyperplasia, results in a redistribution of the loads, favouring the facet joints, and therefore increasing the load on the associated intervertebral disc. Although this has only been demonstrated in a mechanical model, the evidence to-date suggests that an increase of the stress-load on the intervertebral disc locally may enhance the degenerative process in the intervertebral compartment. The possibility that a change in architecture may change the biomechanics of the cervical spine has led to the hypothesis that individuals who have cervical pillar hyperplasia may be predisposed to more biomechanical stress, as is involved in the predominantly accepted theory of the development of degenerative joint disease.

In our preliminary study, although we found no clinically important difference between the global presence/absence of cervical pillar hyperplasia and prevalence of degenerative joint disease, a more sensible explanation of the architectural influence of cervical pillar hyperplasia on cervical spine biomechanics may be segment-specific, meaning that a hyperplastic pillar at a specific cervical level may be related to a higher prevalence of degenerative joint disease at that specific level and/or one segment above or below. We therefore recommended that follow-up research evaluate the segment specific contribution of pillar hyperplasia to the development and severity of degenerative joint disease, because a segmental effect on the biomechanics of the cervical spine is more probable. We assume that the degenerative processes would be a result of the cervical pillar hyperplasia and not the opposite, since cervical pillar hyperplasia has been observed at all ages.

The cervical spine experiences a combination of active mobility and loading stresses, and is therefore, a region of the spine that is frequently affected by progressive degenerative processes. These processes lead to the condition called degenerative disc disease characterized by narrowing of the intervertebral discs, development of osteophytes, intercalary bones and surrounding subchondral sclerosis. Similar radiographic findings affecting the facet and uncovertebral joints can also be present in facet arthrosis and uncovertebral arthrosis, respectively.

Several grading systems have been developed to determine the degree of degeneration radiographically, using signs of subchondral sclerosis, joint space irregularity, decreased joint space and anterior and/or posterior osteophyte formation. degenerative joint disease, osteoarthrosis, or cervical spondylosis, are terms attributed to one or a combination of these findings affecting the disc (degenerative disc disease), uncovertebral, and facet joints (uncovertebral and facet arthrosis) at a particular spinal segment.

Degenerative joint disease is a common, age-related, multi-factorial condition with several theorized etiologies including metabolic, mechanical, inflammatory, and genetic components. This condition affects all joints, especially those that experience chronic biomechanical stresses such as frequent repetitive use and strain, previous trauma and frequent weight-bearing.

The clinical implications of these degenerative processes may include: limitation of head and neck mobility, with or without pain; possible intervertebral foramen encroachment and central canal stenosis, which can result in nerve root or spinal cord compression (radiculopathy and myelopathy respectively); and, although less common, extensive anterior osteophytosis can lead to dysphagia or even vocal fold paralysis. Some controversy exists in the literature with regard to whether radiological findings are related to the patient’s symptoms to a clinically important degree. One long-term follow-up study found that patients’ symptoms correlate with radiographic findings; however, the majority of authors to-date found only a weak relationship between radiographic degenerative changes and pain.

The presence of degenerative joint disease is often confirmed using plain film radiographic findings, with the lateral view being the most informative. The reliability of determining the severity of degenerative joint disease on plain film radiographs in the cervical spine has not been established, but the reliability of detecting the presence or absence of degenerative joint disease has a substantial-to-almost-perfect agreement when assessing the presence/absence of intervertebral disc narrowing, osteophyte formation, zygapophyseal joint, and uncinate process degeneration.

Since the relationship between cervical spine degenerative joint disease and cervical pillar hyperplasia has only been studied ‘globally’ (i.e. cervical pillar hyperplasia was judged to be generally present/absent within the cervical spine as a whole, regardless of whether hyperplastic pillars were detected at one or more levels from C3 to C6), the etiology and clinical relevance of cervical pillar hyperplasia remain unknown. The purpose of this paper, therefore, is to determine if there is a clinically important association between cervical pillar hyperplasia and degenerative joint disease at specific cervical levels, in an age and gender matched sample, and how strong this relationship is between the two conditions, on a by level basis.

The only known clinically relevant result of cervical pillar hyperplasia, as demonstrated in the literature, is its straightening effect on the cervical spine lordosis. Therefore, with such little research on what effect cervical pillar hyperplasia may potentially have on cervical spine biomechanics, it is important to explore any possible clinical consequences of this condition. In our preliminary study, we assessed the possibility that altered spinal biomechanics due to cervical pillar hyperplasia may lead to degenerative changes.

Our present study suggests that a generally weak to moderate segmental association exists between C4 and C5 cervical pillar hyperplasia and adjacent level degenerative disc disease, with the strongest (overall) association demonstrated between C5 cervical pillar hyperplasia and C5–6 degenerative disc disease. The odds of segmental degenerative disc disease occurring together with the adjacent presence of cervical pillar hyperplasia for the overall age categories are approximately two-to-one. Age stratified results demonstrated the same pattern of association (with one exception), even reaching the initially hypothesized moderately-strong association levels in some age categories. Pillar hyperplasia at C4 and C4–5 degenerative disc disease in the 50–54 year age category had the strongest stratified association; nevertheless, generally, the segmental relationship between cervical pillar hyperplasia and degenerative joint disease did not reach the initially proposed association of clinical importance across all age categories.

As mentioned previously, the discrepancies between the C-coefficients and ORs in the younger age subgroups (e.g. 40–54 years) for C4 cervical pillar hyperplasia and C3–4 degenerative disc disease may be due to sample size and/or cervical pillar hyperplasia and degenerative joint disease prevalence inadequacies; these, in turn, can sometimes amplify limitations of the computational formulas themselves. More specifically, naturally occurring low pillar hyperplasia prevalence at C3 and low degenerative joint disease prevalence in adjacent segments, were likely the cause of the lack of statistically significant associations at those respective levels, which in turn, may be due to the likelihood that there are other known contributors to the development of degenerative joint disease; these include trauma, genetic, metabolic, and inflammatory processes, but they were not tested in our study. Nevertheless, our results suggest that cervical pillar hyperplasia is only weakly-to-moderately correlated with the presence of degenerative joint disease; therefore, it may contribute somewhat to the development of degenerative joint disease, but the body may also compensate to some extent for the changes resulting from its slightly aberrant biomechanics. Considering that there are likely several clinically important contributing factors leading to the development of degenerative joint disease, hyperplasia may be but one of several of these. Our findings, when subjected to Coefficient of Determination analysis, suggest that at least in some cervical-spine levels, and in some age categories, cervical pillar hyperplasia may contribute to approximately 9–18% of the development of degenerative joint disease.

Some limitations encountered in this study were poor visualization of C2–3 when assessing films for cervical pillar hyperplasia and degenerative joint disease, poor visualization of C1–2 while assessing for degenerative joint disease, and the sometimes inconsistent presence of hyperplasia in the right and left pillar at a single cervical level. Due to diverging rays of the x-ray beam and small variances in patient positioning, the two articular pillars at any particular level may not be perfectly superimposed on the lateral cervical radiograph, thus allowing the evaluation of each pillar separately for cervical pillar hyperplasia. We were also limited by the lack of any peer-reviewed literature confirming the reliability of evaluating degenerative joint disease severity. Another potential assessment bias in the present study was the fact that one of the assessors, an experienced radiologist, could not be blinded to the presence/absence of cervical pillar hyperplasia while assessing for degenerative joint disease. A future study could eliminate this bias by blinding the assessing radiologist to the purpose of the study.

Another limitation is that the OR sample size estimate was performed ex post facto (after the data were collected), and this, as well as the data analysis (the hypothesis testing part) itself, revealed that the sample sizes in most of the age-specific categories were too small to yield adequate power i.e. statistical significance. Age categories were combined in an attempt to compensate for this, but future studies should endeavour to collect larger samples.

From: Semin Spine Surg. 2007 June; 19(2): 65–71

The intervertebral disc is characterized by a tension-resisting annulus fibrosus, and a compression-resisting nucleus pulposus composed largely of proteoglycan. Both the annulus and the nucleus function in concert to provide the disc with mechanical stability. Early disc degeneration begins in the nucleus with proteoglycan depletion. Quantitative MRI techniques have been developed to non-invasively quantify the earliest degenerative changes that occur within the disc. Our ability to identify and quantify these early biochemical changes will provide a better understanding of the pathophysiology of disc degeneration and facilitate the study of interventions that aim to halt or reverse the degenerative process.

Degenerative disc disease of the intervertebral disc is the most common cause of back-related disability among North American adults. This sometimes debilitating condition affects nearly 12 million people in the United States, and may generate direct and indirect costs exceeding 50 billion dollars annually in health-related expenditures. The radiographic evaluation of patients with degenerative disc disease often begins with plain film radiography and a standard T1- and T2-weighted MRI to assess for structural changes within the nucleus and annulus indicative of disc degeneration including a loss of T2-weighted MRI signal, loss of disc height, disc bulge or herniation, posterior element arthrosis, stenosis, and potential vertebral body compromise. While standard MRI is able to detect these later stage developments, it is not able to provide a quantitative measure of the early changes that characterize early degenerative disc disease. This limitation has led to the search for quantitative, non-invasive measures to evaluate the earliest changes involved in the initiation of the degenerative cascade. Such an imaging tool will be important for the evaluation of the patients with early degenerative disc disease, and also in the assessment of disc regenerative or restorative technologies that aim to halt or reverse the degenerative process.

The intervertebral disc has 3 sub-structures: the annulus fibrosus, which envelops the gel-like nucleus pulposus, and the endplates. The proteoglycan rich nucleus pulposus is comprised of a network of randomly distributed collagen fibrils in a hydrated extra-fibrillar matrix. In contrast, the annulus fibrosus is highly organized. It has 15–40 lamellae (layers) enveloping the nucleus pulposus. In each lamella, collagen fibers are positioned at a 30° angle to the axial axis of the spine. 70–80% of the nucleus pulposus and about 65% of the annulus fibrosus consist of water. After water is removed, an intervertebral disc is composed of collagens (50–70%), proteoglycans (10–50%), and other non-collagenous proteins (up to 25%). Collagen in the annulus fibrosus gives the intervertebral disc its tensile strength. The glycosaminoglycan branches of the proteoglycan are negatively charged, and they bind water. This water-binding property of glycosaminoglycan gives an intervertebral disc its hydrostatic pressure, which resists loading.

The initial stage of degenerative disc disease is marked by proteoglycan degradation and subsequently a reduced capacity of the nucleus pulposus to bind water. In later stages of the disease, morphological changes such as a loss of disc height, annular tears and rim lesions, and osteophyte formation materialize. Previous studies have implicated degenerative disc disease with low back pain. During the intial proteoglycan degradation, the proteoglycans of nucleus pulposus breakdown to clusters of short aggregated and non-aggregated molecules, the glycosaminoglycan content decreases, and the nucleus pulposus’s capacity to bind water reduces. The increased modulus and decreased hydrostatic pressure triggers the nucleus pulposus to undergo a phase change, from a fluid-like material to a more solid-like material. Mechanical function of degenerated motion segments is compromised in all loading conditions. The current standard surgical treatment for lower back pain with advanced intervertebral disc degeneration is lumbar spinal fusion. However, if degenerative disc disease can be detected at an earlier stage, the condition may benefit from emerging alternative treatments (e.g., nucleus replacement, total disc arthroplasty, cell therapy, growth factor therapy). Evaluation of the viability of potential degenerative disc disease therapies and longitudinal monitoring of degenerative disc disease progression demands an objective and quantitative imaging strategy, one that is sensitive to the biochemical changes in the early stages of degenerative disc disease. In this section, we will begin with a brief overview of conventional diagnostic quantitative MRI strategies (T1 and T2 relaxation mapping, dGEMRIC), followed by emerging novel quantitative MRI techniques (sodium, magic echo, and T 1?) that show promise as noninvasive, accurate diagnostic imaging tools for the quantitative assessment of early stage degenerative disc disease.

Standard T1 and T2 relaxation mapping are capable of detecting biochemical changes in the nucleus pulposus but have limitations, including increased scan time, limited dynamic range, and a lack of consistency between in vivo and in vitro values. Recent advancements in MRI, such as sodium MRI, magic echo, and T1? MRI, have been shown to be even more sensitive to PG degradation in the nucleus pulposus. As these quantitative MRI methods are still in the research phase, their efficacy still needs to be more fully evaluated in a clinical setting. However, preliminary clinical data on sodium, magic echo, and T1? MRI have demonstrated great potential to become noninvasive quantitative diagnostic tools for early degenerative disc disease.

From: Arthritis Res Ther. 2008 Aug 5;10(4):R87 [Epub ahead of print]

Chronic and debilitating low back pain is a common condition and a huge economic burden. Many cases are attributed to age related degeneration of the intervertebral disc, however, age related degeneration appears to occur at an accelerated rate in some individuals. We have previously demonstrated biomarkers of cellular senescence within the human intervertebral disc and suggested a role for senescence in intervertebral disc degeneration. Senescence occurs with ageing, but can also occur prematurely in response to stress. We hypothesised that stress induced premature senescence occurs within the intervertebral disc and here we have investigated the expression and production of caveolin-1, a protein that has been shown previously to be upregulated in stress induced premature senescence.

Caveolin-1 gene expression in human nucleus pulposus cells was assessed by conventional and quantitative real-time PCR and caveolin-1 protein expression examined within human intervertebral discs using immunohistochemistry. Correlation between caveolin-1 and p16INK4a biomarker of cellular senescence gene expression was investigated using quantitative real-time PCR.

Caveolin-1 gene and protein expression were demonstrated within the human intervertebral disc for the first time. Nucleus pulposus cells from degenerate discs exhibited elevated levels of caveolin-1 that did not relate to increasing chronological age. A negative correlation was observed between gene expression for caveolin-1 and donor age and no correlation was found between caveolin-1 protein expression and age. A positive correlation was identified between gene expression of caveolin-1 and biomarker of cellular senescence.

Our findings are consistent with a role for caveolin-1 in degenerative rather than age induced changes in the nucleus pulposus. Its expression in intervertebral disc tissue and its association with the senescent phenotype suggests that caveolin-1 and stress induced premature senescence may play a prominent role in the pathogenesis of intervertebral disc degeneration.

Low back pain is a condition that affects a significant proportion of the population, with a lifetime incidence rate in excess of 70% in industrialised nations. It not only impacts on quality of life, but also places a substantial financial burden on the National Health Service and the economy in general due to loss of working days. Many cases of low back pain are attributed to degeneration of the intervertebral disc and imaging studies have indicated a link between intervertebral disc degeneration and low back pain.

To date, no clear mechanism for intervertebral disc degeneration has been identified, although the involvement of both environmental and genetic factors has been proposed. The occurrence of intervertebral disc degeneration increases with age, however a subset of individuals appear to exhibit accelerated degeneration which is independent of age. This has led to speculation that additional factors could play a key role in the development of degeneration in some individuals.

There is increasing evidence that many features of intervertebral disc degeneration, including altered matrix synthesis and enhanced matrix degradation, originate at a cellular level. Cellular senescence is a strong candidate for the prolonged alteration in cellular activity observed during degeneration. Senescence and accompanying alterations in cell function have been implicated in ageing related, degenerative and pathological changes in a variety of tissues, including atherosclerotic plaque development within blood vessels and osteoarthritic alterations to cartilage. Two groups have shown increased staining for senescence associated β-galactosidase in cells from prolapsed and degenerate intervertebral disc cells respectively when compared to non degenerate discs. More recently presented is comprehensive evidence of senescence biomarkers in human intervertebral disc samples, demonstrating increased cellular senescence during intervertebral disc degeneration. In particular, cells from degenerate discs exhibited increased β-galactosidase activity, elevated expression of the cell cycle inhibitor p16INK4a biomarker of cellular senescence gene expression, telomere erosion and a decrease in replicative potential. Furthermore, a correlation was observed between p16INK4a biomarker of cellular senescence gene expression and the expression of matrix-degrading enzymes matrix-metalloproteinase (MMP)-13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), suggesting a role for cell senescence in the molecular processes observed during intervertebral disc degeneration.

Senescence occurs naturally with ageing, but can also occur prematurely in response to stresses (such as exposure to cytokines or oxidative stress) in a number of cell types. Since telomeric erosion and p16INK4a biomarker of cellular senescence gene expression protein are increased in degenerate discs compared to non degenerate age matched samples, we hypothesised that stress induced premature senescence occurs within the intervertebral disc and may be responsible for the accelerated degeneration observed in some individuals.

Caveolae are plasma membrane compartments found abundantly in terminally differentiated cells such as fibroblasts, endothelial and muscle cells. The mammalian caveolin gene family codes for three kDa caveolin proteins, which are integral membrane proteins essential for the structural integrity and function of caveolae. Expression of caveolin-3 is muscle specific, whereas caveolin-1 and caveolin-2 are co-expressed in many cell types. Proposed functions include lipid transport, membrane trafficking and a role in intracellular signalling pathways which stems from the co-localisation of caveolins with a variety of signal transduction molecules. Interestingly, caveolin-1 has been implicated in the senescent phenotype of several cell types including human fibroblasts, lung adenocarcinoma cells, endothelial cells and articular chondrocytes. Moreover, caveolin-1 has been proposed to mediate stress induced premature senescence in murine fibroblasts and human articular chondrocytes in response to oxidative stress and the inflammatory cytokine interleukin-1β, both of which are known to be increased during intervertebral disc degeneration. Here we have investigated the expression of caveolin-1 in human intervertebral discs and correlated its expression with the cell cycle inhibitor and the biomarker of senescence p16INK4a biomarker of cellular senescence gene expression, focusing on the nucleus pulposus as this area was seen to show the most evidence of cell senescence in human intervertebral disc.

This study has shown that caveolin-1 expression in human nucleus pulposis cells is linked to intervertebral degeneration and associated with the senescent phenotype as depicted by increased p16INK4a biomarker of cellular senescence gene expression. Caveolin-1 expression was not linked to increasing chronological age, suggesting a role in accelerated degeneration which could be due to stress induced premature senescence, rather than replicative senescence.

From: J Spinal Disord Tech 2008; 21:430–435

Internal disc disruption’’ is one of the prominent somatic sources of low back pain. MRI is the most common investigation performed to evaluate discogenic pain. Though MRI has advantages of being a sensitive investigation for identifying pathologic anatomy of disc degeneration, its value is limited by its inability to evaluate the physiologic status of the disc. Studies have questioned the specificity of MRI in diagnosing discogenic pain and have reported degenerative changes in 26% to 57% of asymptomatic volunteers. Discography is a useful tool to identify the painful disc responsible for patient’s symptoms. In evaluation of discogenic low back pain there has been a debate as to whether discography should replace MRI. Proponents of discography believe that it is an invaluable tool for identifying the pathologic disc producing pain. Critics believe that discography is an invasive investigation and has no place in modern practice.

Over the last decade there has been a vast improvement in the quality of MR images. Attempts have been made to identify features on MRI scans that would correlate with patient’s symptoms and would potentially eliminate the need for discography. Such features are the vertebral end plate changes described by Modic and the high intensity zone described by Aprill and Bogduk. The implications of these findings have been a subject of controversy.

This is a prospective study aimed at correlating the results of discography with new MRI classification in a consecutive series of patients with disabling low back pain considered for spinal surgery. In addition, we also aimed to compare vertebral end plate changes and high intensity zones seen on MRI with discography findings.

Woodend MRI Classification
Grade 1: White nuclear signal, normal height bean shape nucleus, annular margins well defined, no tears.
Grade 2: Speckled nuclear signal, height reduced less than 10%,distortion of nuclear shape, small radial tears not reaching the PLL on axial views.
Grade 3: Speckled or dark nucleus, height reduced by 10%-50%, radial tears extending upto or torn PLL on sagittal/axial views.
Grade 4: Dark nucleus, height reduced by greater than 50%, no difference between appearance of annulus and nucleus ± complex tears.

Disc Morphology Grading
Grade 1: cotton ball or lobular appearance of disc with no tears.
Grade 2: disc with fissures or clefts in the nucleus or inner annulus.
Grade 3: degenerate disc with radial fissures leading to outer edge of the annulus.
Grade 4: disc with complete radial fissure.

Internal disc disruption was described by Crock as a condition causing back pain without nerve root compression. Tears within the annulus fibrosus are a major hallmark of degenerative intervertebral disc disease. Tears within the annulus evoke an inflammatory response, which leads to degradation of disc matrix and chemical irritation of nerve fibers within the outer annulus. Discogenic pain is a mechanical, nonradicular pain with a somatic pattern. Therefore, the use of symptoms and signs to identify the symptomatic degenerative disc level has limited value. A method for investigating discogenic pain cannot be considered reliable unless there is a confirmed relationship between its findings and a patient’s symptomatology

Lindbolm first introduced discography in 1944. Holt raised the first major challenge to this technique in 1968. Holt reported false-positive findings in 37% of patients in a study on asymptomatic prison inmates. However, following a study carried out by Walsh et al in 1990 under more stringent conditions, doubts were raised regarding Holt’s findings. Walsh et al carried out discography in 10 asymptomatic volunteers and reported no false-positive result. Adams et al performed a cadaveric study and proposed a discography classification, which has been used, in a modified form, in this study. The Dallas Discogram Description described by Sachs et al is based on computed tomography scan after discography. We believe that this exposes patient to unnecessary radiation and increases cost without any additional benefit. The morphology of the disc as revealed by discography is irrelevant. In our study, we have used concordant pain on discography as a guide to the pain source. The analysis for sensitivity and specificity has been performed after excluding discs with discordant pain. As the investigation is performed under local anesthetic we believe that the patient’s response can be reliable.

In the late 1980s, when MRI became popular among spinal surgeons, a number of studies questioned the utility of discography in discogenic pain. Gibson et al reported 88% correlation between findings of MRI and discography in 50 patients. Discography was carried out under sedation and the authors believed that this was an unreliable sign. Schneiderman et al concluded that MRI was 99% accurate as compared with discography. In both these studies the correlation of MRI was with disc morphology rather than pain. Simmons et al reported that 37% of the discs reported abnormal on MRI were asymptomatic on awake discography. Linson and Crowe reported 94% correlation between MRI and discography. In their study, only 53% of the degenerative discs were found to be symptomatic. They concluded that discography remains the examination of choice for differentiating between symptomatic and asymptomatic discs. Collins et al reported morphologic correlation between discography and MRI in 89.5% cases. Only 13 of 73 discs were symptomatic and 10 had degeneration with annular bulges on MRI. Osti et al in a study on 108 intervertebral discs found that of the 39 symptomatic discs only 27 had abnormal signals on MRI. They concluded that discography is a more accurate investigation to detect symptomatic disc. Horton and Daftari correlated disc signals and annular bulges with pain reproduced at discography and concluded that MRI does not reliably predict or replace discography.

In this study, we have attempted to use an MRI classification system that will help predicting pain and allow comparison of various disc appearances. This classification embraces various aspects of disc morphology such as MRI signal, disc height, and annular tear in combination rather than considering them as individual entities. The classification uses the carefully aligned axial and sagittal images on MRI, unlike most of the previous studies in which only sagittal scans were used. We now use these scans routinely. The interobserver and intraobserver reliability of the classification system is good. The classification system can be used to communicate status of disc morphology and has a potential as a research tool. There is good correlation between the grades of degenerative disc on discography and the MRI classification system. In our study, we also found that grades 3 and 4 disc morphology has a 81% sensitivity and 80% specificity in predicting discogenic pain. We postulated that annular tears would predict a disc to be painful and included these as one of the criteria for pain prediction on MRI. These tears are best visualized on axial scans. The majority of the discs with annular tears were grade 3 or grade 4. Of the 25 grade 2 discs 14 had annular tears and 12 produced concordant or discordant pain. The presence of grade 3 or grade 4 disc on MRI scan or grade 2 with annular tear increased the sensitivity of MRI scan in detecting a painful disc to 94%.

There has been considerable interest in high intensity zones as predictors of painful lumbar intervertebral discs. Aprill and Bogduk who considered it to represent inflammation in the annulus secondary to trapped nuclear material and reported a sensitivity of 82% and specificity of 89%. Schellhas et al and Lam et al found high intensity zone to be a reliable predictor. Ricketson et al11 did not find significant correlation between high intensity zone and concordant disc pain. Ito et al described a sensitivity of 52% and specificity of 90% for concordant disc pain. The sensitivity and specificity of high intensity zone in our study is close to those reported by Saifuddin et al and Smith et al. Vertebral end plate has been identified as a possible source of low back pain. Braithwaite et al and Ito et al reported low sensitivity and high specificity for end plate changes which closely corresponds to that in our study.

In 25% of the patients, the findings of MRI and discography did not correlate. This is due to low specificity of MRI in detecting the painful level. There were 3 discs, which were grade 1 on MRI and produced concordant pain and 12 grade 3 or grade 4 discs, which were not painful. We agree with Simmons et al that, in current practice, discography has a place as it can complement the interpretation of MRI findings and help to determine management of chronic low back pain. There were 18 discs, which produced discordant pain in our study. A disc with discordant pain is still painful disc though not necessarily causing the patient’s major symptoms.

In our study, the group of patients who had previous surgery had similar discography and MRI correlation. We find MRI is also useful in evaluation of this group of patients with previous spinal surgery. Improvements in biomaterials and scanning techniques allow good quality MRI scans in patients with previous instrumentation and artifacts do not hamper assessment of disc morphology.

The use of discography has a limitation that pain on discography is subjective and dependent on interaction between patients and surgeons/radiologists, and has to be interpreted as such. We studied a selected group of patients considered for spinal surgery. We believe that discography is a preoperative investigation and should be performed only when the diagnosis of discogenic pain is highly probable as determined by systematic clinical examination, nonoperative treatment has failed, and a decision is made to proceed to surgery. Our study does not address the implications for management of patients. This cohort of patients is being followed prospectively and their long-term outcome will answer whether these findings have implications for patient’s quality of life outcome after surgical treatment. We also believe that in future techniques, which can stimulate disc in noninvasive manner while performing MRI, will benefit assessment of discogenic pain. This will improve the specificity of MRI. Yrjama et al have reported such techniques but these have not been reported from other centers.

From: Spine. 2008 Aug 1;33(17):1821-8.

A cohort of young, healthy New Zealand White rabbits was followed longitudinally with serial magnetic resonance imaging analysis and terminal analysis of histologic changes and gene expression to examine the changes observed during normal aging in the intervertebral disc. Although there is a correlation between aging and the onset of intervertebral disc degeneration, evidence suggests that distinct pathways are involved in these processes. Our group has characterized a reproducible rabbit model of intervertebral disc degeneration by magnetic resonance imaging, radiograph, histology, and mRNA expression. However, no similar analysis has been performed longitudinally for intervertebral disc aging to allow comparison of these 2 important processes.

Four skeletally mature female NZW rabbits were housed for 122 weeks, and lumbar spine MRIs were characterized serially. Histologic and quantitative gene expression analysis of the nucleus pulposus of these aging animals was performed, and compared with adult and young rabbits. Mean magnetic resonance imaging index decreased by <25% through 120 weeks. The histologic analysis showed changes in cell composition, with abundant notochordal cells in the young, chondrocyte-like cells and notochordal cells in the adult, and clusters of hypertrophic chondrocytes in the aging discs. The PCR analysis of the nucleus pulposus showed that gene expression of collagen decreased, whereas that for proteoglycans increased with aging. BMP-2, TIMP-1, and SOX-9 expression was significantly lower in the young compared with adult discs and TGF-beta1 demonstrated lower gene expression in young and aging animals.

Although dramatic cellular changes were observed, age-related magnetic resonance imaging changes occurred in this rabbit model of normal aging at a much slower rate than in a previous injury model of degeneration. In addition, the gene expression analysis of the nucleus pulposus demonstrated remarkable differences between aging and injury induced degeneration. These results suggest that aging and injury contribute uniquely to the process of intervertebral disc degeneration.

From: Annals of the Rheumatic Diseases 2007;66:330-333

Peripheral joint osteoarthritis is characterised radiologically by the presence of osteophytes, subchondral sclerosis and joint space narrowing. Joint space narrowing is due to cartilage loss, whereas both subchondral sclerosis and osteophytes are hypertrophic responses of bone, thought to arise directly either to cartilage loss or to biomechanical stress. The pathophysiology and hence the inter-relationship of these features are however not well understood. Recently, strong associations between the presence of enthesophytes, osteophytes and bone sclerosis at various joint sites have been shown. Partly on the basis of these observations, it has been suggested that some individuals may be more likely to develop bone formation in response to disease occurrence. We looked at a series of lumbar spine radiographs and characterised the severity of the component radiographic features. Although the pathology of disc degeneration differs from peripheral joint osteoarthritis, we hypothesised that if there was a predisposition to develop new bone formation in the form of osteophyte or sclerosis in response to mechanical stress, there would be a strong association between increasing severity of the features of new bone formation. The aim of this study was to determine the strength of the association between increasing severity of osteophytes and end-plate sclerosis, and the association between both these features and disc space narrowing in the lumbar spine.

In this study, we found that increasing severity of all three radiographic features of lumbar disc degeneration was associated with increasing severity of the other features, although the association was strongest for osteophytes and end-plate sclerosis, and was stronger within than between vertebral levels. There are some methodological limitations that need to be considered when interpreting the findings. The response rate for participation in the study was 61%. Those who attended for screening could have differed with respect to the frequency of disc degeneration than those who did not attend. Given, however, that the analysis of the inter-relationships between radiographic features was based on an internal comparison of responders, non-participation bias is unlikely to have had a major effect on the observed findings.

The semiquantitative approach used here to characterise the individual radiographic features is subject to errors of precision. Formal assessment of intraobserver variability as determined by was good. At the time of assessment, the observer was not aware of any possible difference in pairwise associations between features and any errors in classification of the features likely to have been non-directional, and would tend to reduce the chance of finding true associations.

As with peripheral osteoarthritis, the pathogenesis of intervertebral disc degeneration remains poorly characterised. Degenerative changes within the disc may result in an alteration of its mechanical properties, increased flexibility and decreased disc height, which in turn contribute to changes in the local stress/strain state within the disc. Also, as has been considered for peripheral osteoarthritis, the bone may be the primary trigger responding to lifelong stress with hypertrophy and stiffening, and transmitting increased load to the intervertebral disc. In peripheral osteoarthritis, there is some evidence that increased bone mass is a predictor of radiographic osteoarthritis. It has also been shown that generalised osteoarthritis is associated with increased levels of insulin-like growth factors in extracts of cortical bone from the iliac crest.

If osteophytes and end-plate sclerosis are independent and separately related to narrowing of the disc, then we could hypothesise that as disc space narrowing increased, the severity of these features would increase in parallel. However, we observed that the proliferative features were more likely to be related in terms of severity than either separately with disc space narrowing.

There are few data concerning inter-relationships between component radiographic features of lumbar disc degeneration in the literature. In a Japanese study, there were significant correlations between osteophytes, end-plate sclerosis and disc space narrowing in the lumbar spine, although data relating to these features were pooled rather than considered by vertebral level. As in our study, the association between osteophytes and end-plate sclerosis was stronger than either of the other pairwise correlations. In a study of twins using magnetic resonance imaging, a strong correlation was seen between the same measurements (including disc height and osteophytes) across all vertebral levels within the cervical and lumbar spine, but a weaker correlation when the same features were compared between the cervical and lumbar spine.

In a series of paleopathological specimens, it was observed that individuals who had a tendency to form enthesophytes were more likely to have both osteophytes and sclerosis present at peripheral joint sites. These data have been considered to be consistent with a bone proliferative response to disease occurrence. Although the pathologies of disc degeneration and peripheral osteoarthritis are different, our data in relation to severity of osteophytes and sclerosis would be consistent with this. Further research is necessary to determine the factors affecting the occurrence and severity of these features.

We have previously shown in this population sample an association between radiographic features of disc degeneration and back pain although disc space narrowing was more strongly associated than the other features. All three features increased in frequency with age. We found evidence also of an association between bone mineral density at the femoral neck and the presence of vertebral osteophytes and end-plate sclerosis, although not disc space narrowing. However, further prospective data are required both to confirm our findings and to determine the temporal nature of the observed associations.

From: Spine. 2006 May 20;31(12):1327-31

A retrospective study was conducted to investigate relationships between severe disc degeneration and segmental instability in cervical spondylotic myelopathy and to discuss surgical treatment for cervical spondylotic myelopathy with severe disc degeneration. Information on relationships between segmental instability and spinal cord compression in cervical spondylotic myelopathy with severe disc degeneration is scarce. Radiographs and magnetic resonance images of patients with cervical spondylotic myelopathy with (n = 42) and without (n = 75) severe disc degeneration were reviewed retrospectively. Cervical instability and spinal cord compression factors were analyzed. Outcomes of anterior cervical decompression and fusion and expansive laminoplasty were evaluated in medical records of follow-up clinics.

Segmental instability was found in 71.4% of patients with severe disc degeneration and 22.7% of patients without severe disc degeneration. Spinal cord compression was found at the intervertebral space of severe disc degeneration and upper adjacent disc space. The recovery rate of anterior cervical decompression and fusion and expansive laminoplasty was 60.8% and 57.1%, respectively. The upper adjacent vertebra above severe disc degeneration has inclination of segmental instability. There is static spinal cord compression in intervertebral spaces of severe disc degeneration and dynamic compression in upper adjacent intervertebral spaces. Multilevel anterior cervical decompression and fusion or expansive laminoplasty should be used for surgical treatment.

From: Spine. 1994 Mar 1;19(5):502-6

Median frequency parameters of myoelectric signals were studied in 25 patients with osteoarthritis of the cervical spine and in 25 normal subjects. The median frequency parameters included initial median frequency and slope of the median frequency during 20%, 50%, 80%, and 100% of maximum voluntary contractions. The subjects performed sustained, isometric constant-force contractions of forward and backward bend of the cervical spine. The median frequency signals were obtained from the anterior (sternocleidomastoid) and posterior (upper trapezius) neck muscles. The results showed that at moderate and high forces (i.e., 50%, 80%, and 100% maximum voluntary contractions ) the anterior neck muscles in patients with osteoarthritis of the cervical spine fatigued faster than those of normal subjects. The posterior neck muscles in patients fatigued faster compared to normal subjects at high force levels (i.e., 80% and 100% maximum voluntary contractions ). This indicates a higher fatigue of the anterior and posterior neck muscles associated with arthritic changes of the cervical spine. Rehabilitation programs must consider these muscular changes to obtain optimal outcomes.

From: Am J of Physical Anthrop. 136:318–326 (2008) The extent to which degenerative joint disease in bone may be seen as an indicator of mechanical or occupational stress has long been a focus of debate within osteoarchaeology. While some studies of paleopathology continue to use degenerative joint disease as a predictor of specific activity patterns, most urge caution. Clinical studies have failed to demonstrate a simple relationship between degenerative joint disease and specific patterns of movement or activity. Certain aspects of degenerative joint disease appear to be related to age, whereas others appear to be related to sex, genetic inheritance, or body weight. degenerative joint disease 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. 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. Not surprisingly, this complexity has tended to discourage consideration of the biomechanical implications of degenerative joint disease, even where the presence and pattern of such pathology is well documented.

The vertebral column is one region of the skeleton that has become a focus of interest for paleopathological study into degenerative joint disease. 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. 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 can damage the articular surfaces of the apophyseal joints, possibly precipitating degenerative joint disease, and the pattern of cartilage damage may be indicative of the type of mechanical overload involved. Palaeopathological studies have suggested that degenerative joint disease occurs in the apophyseal joints of the cervical spine, which is subjected to relatively wide range of motion and also in the lower lumbar spine, which is heavily loaded. It is not clear if degenerative joint disease 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, especially when specimens are loaded to simulate a lordotic posture, and clinical studies confirm that lumbar disc degeneration increases the risk of degenerative joint disease in the apophyseal joints. 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. However, there is little firm evidence to support this suggestion.

Given this complex background, it is perhaps not surprising that degenerative joint disease 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. 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, but it can be achieved indirectly, by calculating the compressive force transmitted by the adjacent intervertebral disc. Here this technique will be used to compare load-bearing in the apophyseal joints of elderly cadavers with direct evidence of degenerative joint disease in the same joints, assessed from morphological changes in cartilage and bone.

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%. 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. 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, 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.

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 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, and considerable spinal compression. 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. 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. Lumbar apophyseal joints also resist axial rotation, and they couple axial rotation with lateral bending in a posture-dependent manner. 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 degenerative joint disease in the lower spine, and the results presented here provide more detailed evidence which helps to explain how this occurs, at least in relatively elderly individuals. 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. 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 processes and the laminae below. 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 degenerative joint disease 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. 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, 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, 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.

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, and this height loss is known to increase compressive load-bearing by the apophyseal joints. 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. In moderately flexed postures, the apophyseal joints resist very little compressive force, even when the discs are narrowed. In this way, the relationship between degenerative joint disease 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%, reduces pressure in the nucleus pulposus by 10%, and approximately doubles load-bearing by the apophyseal joints.

The results of this present experiment suggest that degenerative joint disease in the apophyseal joints of the elderly human thoracolumbar spine can be strongly suggestive of biomechanical environment in life. Even the observation of mild degenerative joint disease 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. 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. For studies of degenerative joint disease, however, such an approach provides an essential grounding. 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. 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, both within populations and between them. 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. The relatively large size of the neural arch in australopithecines, coupled with the patterning of degenerative joint disease 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. 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, the comparative, experimental approach presented here can nevertheless yield insights into human biomechanics in archaeological populations.

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.

From: Isr Med Assoc J. 2008 May;10(5):365-9

Balneotherapy is an established treatment modality for musculoskeletal disease, but few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases. To assess the effects of balneotherapy on chronic musculoskeletal pain, functional capacity, and quality of life in elderly patients with osteoarthritis of the knee or with chronic low back pain. The 81 patients in the study group underwent a 1 day course of 30 minute daily baths in mineral water. Changes were evaluated in the following parameters: pain intensity, functional capacity, quality of life, use of non-steroidal anti-inflammatory or analgesic drugs, subjective disease severity perceived by the patients, investigator-rated disease severity, and severity of pain perceived by the patients. We analyzed the results of 76 subjects as 5 did not complete the study.

Compared to baseline, all monitored parameters were significantly improved by balneotherapy in both investigated groups. Moreover, the favorable effect was prolonged for 3 months after treatment. This study showed that balneotherapy is an effective treatment modality in elderly patients with osteoarthritis of the knee or with chronic low back pain, and its benefits last for at least 3 months after treatment.