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Discs & Nucleus

Nucleus pulposus degeneration and extracellular matrix degradation — pathophysiology of disc height loss and mechanical load redistribution in IDD.

Overview

Early disc degeneration related to tumor treatment is observed in the intervertebral discs of radiotherapy-treated childhood brain tumor survivors [1], with lesions of the lumbar intervertebral discs occurring in older children and adolescents [3]. The prognosis for these lumbar lesions in older children and adolescents is good, as nearly all patients recover following conservative treatment [3]. In contrast, anterior rupture of the disc represents a rare lesion that may be identified by discography when other investigations are inconclusive [6]. Information obtained from discography for anterior rupture allows for a more effective operative approach [6].

Surgical intervention requires strict patient selection, as the first and fundamental predictor of success is the identification of only those patients presenting with classic signs and symptoms of the disorder [4]. While short-term studies demonstrate similar clinical improvements for both disk replacements and fusion procedures at up to 2-year follow-up [10], chemonucleolysis remains an effective and safe alternative to surgical excision of a disc for herniated nucleus pulposus in adolescents [23]. Full endoscopic transforaminal discectomy is also a safe and effective surgical intervention for treating herniated lumbar discs in the context of obesity [24].

Pathological severity correlates with significant differences in the distribution of MR signal intensity within the nucleus zone of intervertebral discs [7]. Surgical defects in the disc can lead to disc collapse, fibrosis, and protrusion, yet fusion is not achieved by curettage alone for such defects [29]. To ensure data reliability, specific basal media are recommended as standard for disc cell culture to harmonize preclinical study results [27].

Anatomy & Pathophysiology

Diagnostic Imaging: MRI signal distribution indices discriminate between scoliosis and spondylolisthesis severities and provide essential information on disc composition and structure regardless of pathology [5]. Magnetic resonance diffusion tensor imaging (DTI) quantitatively assesses biochemical composition changes within the intervertebral discs [9]. Measurement of thoracic kyphosis (TK) with T2 on standing whole spinal radiographs results in a greater measurement error of up to 6.6° compared to upright computed tomography images [50].

Biomechanics & Loading: Repetitive loading of the spine has demonstrable short-term and possibly permanent effects on the lumbar intervertebral disk, as suggested by T2* values [11]. A strict mathematical definition of the neutral zone based on spinal motion segment compliance is objective, conceptually correct, and does not depend on arbitrarily chosen criteria [33]. Computational accuracy and efficiency of in-silico studies can be improved in lumbar finite element analysis models constructed using smoothened surfaces with measured and calibrated relative nucleus position and cross-sectional area ratio [40]. No mechanical failures were observed in a viscoelastic disc after 30-million-cycle intervals, which simulates approximately 80 years of lumbar-bending motions [31].

Surgical Implications & Reconstruction: Excision of the capsule and cartilage of the facets increases motion between lumbar vertebrae, which may increase tensile strain in a graft and predispose to non-union in lumbar arthrodesis without instrumentation [43]. The ipsilateral approach in unilateral bilateral endoscopic spine surgery has a low facet joint reduction rate, minimum soft tissue injury, and precisely identifies the midline of the central spinal canal [44]. Disc prostheses require a variable center of rotation for flexion/extension below disc level with the capability to move along the x- and y-axes during motion [42]. Disc prostheses require a second completely independent center of rotation for lateral bending above disc level to closely replicate in-vivo motion [42]. A 5 mm implant height provides biomechanical properties similar to intact specimens in total cervical disc replacement, whereas larger heights alter facet joint mechanics [32].

Regeneration & Repair: Distraction accelerated the lengthening of the vertebrae and the heightening of the intervertebral disc without observable degeneration or decline in mechanical performance under these distraction conditions [36]. Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc [48]. Low-tension traction further promotes the regeneration and repair of intervertebral discs [48]. PGA-HA nucleus-implants were able to restore biomechanical characteristics of spinal segments in flexion/extension after nucleotomy [46]. Sealing the annulus defect effectively prevented herniation of the implant in polymer-based biomaterial restoration of spinal stability after nucleotomy [46].

Cellular & Systemic Factors: In vitro manipulation of disc cells allows testing of how disc cells from given individuals respond when grown in environments directing them to have either spindle- or rounded-shapes [18]. Vertebral bone marrow fat is associated with sagittal spine alignment, which may serve as a new additional explanation for the association of sagittal alignment with spinal degeneration [49]. Different spinal subtypes exhibit characteristics of lumbar disc degeneration at specific levels that vary with age [2].

Clinical Examination: General principles for physical examination of the spine include inspection, palpation, range of motion testing, and neurologic evaluation to identify spinal pathology, nonspinal conditions, and signs of symptom magnification [38].

Classification

Disc Degeneration Phenotypes: Early signs of disc degeneration related to tumor treatment are visible in the intervertebral discs of survivors [1]. Different spinal subtypes exhibit characteristics of lumbar disc degeneration at specific levels with age [2]. Significant differences exist in the distribution of MR signal intensity within the nucleus zone of intervertebral discs due to pathology and its severity [7]. MRI signal distribution indices provide essential information on the composition and structure of the discs regardless of the pathology considered [5] and are able to discriminate between scoliosis and spondylolisthesis and their severities [5]. An MRI protocol combined with principal component analysis and agglomerative hierarchical clustering are promising tools to classify degenerated intervertebral discs [30].

Herniation Patterns: Most herniations of a lumbar intervertebral disc occurring before the age of sixty years are protrusions of the nucleus pulposus [8]. After the age of sixty years, prolapse of the anulus fibrosus predominates in the few herniations that occur [8]. Anterior rupture of the disc is a rare lesion that can be identified by discography when other investigations are inconclusive [6].

Osteogenic and Cellular Characteristics: The osteogenic potential of degenerated intervertebral discs appears to increase with the severity of degeneration [12]. This potential is greater in the tissue near the spinal canal than in tissue in the inner portion of the disc [12]. Various cell death patterns affect the disease progression of intervertebral disc degeneration [17]. Estrogen receptor-β is expressed and localized in annulus cells of the human intervertebral disc, where 17-β-estradiol has a mitogenic effect in vitro [19].

Infant Disc Composition: The proteoglycans of the human infant intervertebral disc share a basic structure with those of hyaline cartilage but differ in dimensions [41]. The nucleus pulposus of the human infant intervertebral disc contains less protein and smaller aggregates than the annulus fibrosus and cartilage end-plate [41].

Other Considerations: The first and fundamental predictor of success in disc surgery is the selection of only patients who have the classic signs and symptoms of that disorder [4]. A 4-grade fat infiltration system is more effective than a 3-grade fat infiltration system in the determination of the level of fat infiltration in the paraspinal muscles [52] and in the prediction of lumbar disc herniation [52].

Clinical Presentation

The clinical evaluation of disc pathology begins with a thorough history and physical examination to identify classic signs and symptoms, which remain the fundamental predictor of surgical success [4]. In pediatric populations, lesions of the lumbar intervertebral discs may occur in older children and adolescents, often presenting as narrowing of the intervertebral-disc space. This condition is a destructive lesion involving the disc with minimum vertebral involvement, similar to osteomyelitis but distinct enough to be regarded as a separate entity [22]. The prognosis for these lesions is favorable, with nearly all patients recovering via conservative treatment [3]. Conversely, early signs of disc degeneration related to tumor treatment are observable in the intervertebral discs of childhood brain tumor survivors following radiotherapy [1].

Imaging and Diagnostic Modalities

MRI Signal Analysis: Magnetic resonance imaging provides essential data on disc composition and structure regardless of the specific pathology [5]. MRI signal distribution indices can discriminate between scoliosis and spondylolisthesis and assess their severities [5]. Significant differences exist in the distribution of MR signal intensity within the nucleus zone due to pathology and its severity [7]. The presence of a high-intensity zone (HIZ) on a lumbar MRI T2-weighted image indicates abnormal disc morphology [21]. Furthermore, magnetic resonance DTI quantitative imaging offers a means to assess biochemical composition changes within the intervertebral discs [9].

Discography and Special Tests: Anterior rupture of the disc is a rare lesion identifiable by discography when other investigations are inconclusive [6]. With current techniques and standardized pain assessment methods, lumbar discography is a highly reliable and specific diagnostic test [16]. However, conflicting evidence notes that discograms have yet to be proved a reliable diagnostic aid in the treatment of back, neck, or nerve-root pain [20]. The ultrasound-guided disc pain induction test may assist in diagnosing disc degeneration and identifying culprit lesions even when multiple discs exhibit degenerative findings [13].

Pathophysiology and Clinical Correlation

Disc herniation patterns vary significantly by age; most herniations occurring before age sixty are protrusions of the nucleus pulposus, whereas after age sixty, prolapse of the anulus fibrosus predominates [8]. Various cell death patterns influence the disease progression of intervertebral disc degeneration [17]. Despite the ability to visualize pathology, there is no correlation between the proportional size of a prolapsed intravertebral disc and the degree of disability or leg pain [15]. Consequently, the symptoms experienced by patients should be the primary concern in deciding to perform a discectomy [15]. Clinicians must remain vigilant, as disc sequestration mimicking a tumor is difficult to diagnose preoperatively [14]. Additionally, different spinal subtypes exhibit characteristics of lumbar disc degeneration at specific levels correlated with age [2].

Investigations

MRI: MRI signal distribution indices discriminate between scoliosis and spondylolisthesis and their severities, providing essential information on disc composition and structure regardless of pathology [5]. The distribution of MR signal intensity within the nucleus zone shows significant differences due to pathology and its severity [7]. New quantitative MRI sequences, including T2 mapping, T1ρ mapping, and MR spectroscopy, evaluate anatomical and physiological changes of intervertebral disc degeneration in greater detail than conventional T2-weighted imaging (T2WI) [55], though these values do not directly correlate with low back pain [55]. Magnetic resonance DTI quantitative imaging assesses biochemical composition changes and offers valuable insights for clinical diagnosis and evaluation of therapeutic efficacy in disc degenerative diseases [9]. An HIZ on a lumbar MRI T2-weighted image indicates abnormal disc morphology [21] and disc degeneration [47], potentially serving as a specific indicator for the physical diagnosis of discogenic low back pain [47]. An MRI protocol combined with principal component analysis and agglomerative hierarchical clustering is a promising tool to classify degenerated intervertebral discs [30].

Discography: Anterior rupture of the disc is a rare lesion identifiable by discography when other investigations are inconclusive; information obtained from discography in such cases allows for a more effective operative approach [6]. With current techniques and standardized pain assessment methods, lumbar discography is a highly reliable and specific diagnostic test [16]. However, discograms have yet to be proved a reliable diagnostic aid in the treatment of back, neck, or nerve-root pain [20].

Other Considerations: Signs of early disc degeneration related to tumor treatment are seen in the intervertebral discs of radiotherapy-treated childhood brain tumor survivors [1]. Different spinal subtypes exhibit characteristics of lumbar disc degeneration at specific levels with age [2], and lesions of the lumbar intervertebral discs may occur in older children and adolescents with a good prognosis where nearly all patients recover via conservative treatment [3]. T2* values suggest that repetitive loading of the spine has demonstrable short-term and possibly permanent effects on the lumbar intervertebral disk [11]. The osteogenic potential of degenerated discs increases with degeneration severity and is greater in tissue near the spinal canal than in the inner portion of the disc [12]. The ultrasound-guided disc pain induction test may help diagnose disc degeneration and identify culprit lesions even when multiple discs exhibit degenerative findings [13]. Disc sequestration mimicking a tumor is difficult to diagnose preoperatively [14]. A disorder characterized by narrowing of the intervertebral-disc space in children is a destructive lesion involving the disc, similar to osteomyelitis but with minimum vertebral involvement, and should be regarded as a separate entity [22].

Treatment

Non-Operative

Conservative management is the primary approach for lumbar disc lesions in older children and adolescents, where nearly all patients recover [3]. Spontaneous resorption of lumbar disk herniation offers a promising non-surgical avenue, driven by mechanisms including inflammation, neovascularization, and macrophage infiltration [35]. Chemonucleolysis serves as an effective and safe alternative to surgical excision for herniated nucleus pulposus in adolescents [23]. Repeat steroid injections are a justifiable treatment for symptomatic patients with lumbar or cervical disc herniation whose symptoms remain unrelieved after the first injection [39].

Operative

Indications: The first and fundamental predictor of success in disc surgery is the strict selection of patients presenting with classic signs and symptoms of the disorder [4]. Symptoms experienced by patients should be the primary concern in deciding to perform discectomy, as there is no correlation between the proportional size of a prolapsed intravertebral disc and disability or leg pain [15]. Preoperative evaluation must clearly identify the exact level of disc herniation; in cases where this is unclear, the presence of the jerk reflex can indicate which nerve root is under tension by the abnormal disc material [45]. Anterior rupture of the disc is a rare lesion identifiable by discography when other investigations are inconclusive, facilitating a more effective operative approach [6]. Disc sequestration that mimics a tumor presents a diagnostic challenge preoperatively [14].

Surgical Approach / Technique: Full endoscopic transforaminal discectomy remains a safe and effective surgical intervention for treating herniated lumbar discs, even in the context of obesity [24]. Surgical defects in the disc can lead to collapse, fibrosis, and protrusion, but fusion is not achieved by curettage alone [29]. Intradiscal injection of nucleus pulposus (NP) cells following endoscopic discectomy appears safe and could be considered an effective therapeutic method for chronic low back pain with no recurrence based on two-year follow-up MRI findings [37]. Historically, complete removal of the nucleus pulposus and degenerated disc portion combined with a Hibbs type of spine fusion yields good or excellent results in a very high percentage of patients, provided cases are well selected, operations are performed with skill and gentleness, and an appropriate postoperative regimen including exercises is followed [54].

Adjuncts: Magnetic resonance diffusion tensor imaging (DTI) quantitative imaging provides a means to assess biochemical composition changes within the intervertebral discs for clinical diagnosis and evaluation of therapeutic efficacy [9]. Significant differences exist in the distribution of MR signal intensity within the nucleus zone of intervertebral discs due to pathology and its severity [7]. With current techniques and standardized pain assessment methods, lumbar discography is a highly reliable and specific diagnostic test [16].

Other Considerations: Early disc degeneration related to tumor treatment can be observed in the intervertebral discs of childhood brain tumor survivors [1]. Various cell death patterns affect the disease progression of intervertebral disc degeneration, offering new perspectives and potential clinical intervention strategies for prevention and treatment [17]. Gene therapy has shown much promise in the treatment of intervertebral disk degeneration, with many new targets and vectors being investigated [34]. There is a great unmet need for regenerative solutions that not only treat symptoms but also reverse or halt the progression of intervertebral disc degeneration [53]. The nucleus pulposus can regenerate following chymopapain injection, with restoration of disc height and normal histology by six months [26]. Short-term studies demonstrate similar clinical improvements for both disk replacements and fusion procedures at up to 2-year follow-up [10].

Complications

Disc Degeneration and Pathology: Early signs of disc degeneration related to tumor treatment are observed in the intervertebral discs of radiotherapy-treated childhood brain tumor survivors [1]. Lesions of the lumbar intervertebral discs may occur in older children and adolescents, with a prognosis that is generally good as nearly all patients recover with conservative treatment [3]. Different spinal subtypes exhibit characteristics of lumbar disc degeneration at specific levels with age [2]. MRI signal distribution indices provide essential information on the composition and structure of the discs regardless of the pathology considered and can discriminate between scoliosis and spondylolisthesis and their severities [5]. The ultrasound-guided disc pain induction test may help diagnose disc degeneration and identify culprit lesions, even when multiple discs exhibit findings of degeneration [13]. Repetitive loading of the spine has demonstrable short-term and possibly permanent effects on the lumbar intervertebral disk, as suggested by T2* values [11].

Herniation Patterns and Surgical Selection: Most herniations of a lumbar intervertebral disc that occur before the age of sixty years are protrusions of the nucleus pulposus, whereas after the age of sixty years, prolapse of the anulus fibrosus predominates in the few herniations that occur [8]. It should not be assumed that degenerative changes always precede disc herniation [28]. Experimental ruptures of intervertebral discs in rats' tails take place without change in the nucleus pulposus [56]. The first and fundamental predictor of success in disc surgery is the selection of only patients who have the classic signs and symptoms of that disorder [4]. There is no correlation identified between the proportional size of a prolapsed intravertebral disc with disability or leg pain, and the symptoms experienced by patients should be the primary concern in deciding to perform discectomy [15].

Biological and Molecular Factors: The osteogenic potential of degenerated intervertebral discs appears to increase with the severity of degeneration and is greater in the tissue near the spinal canal than in tissue in the inner portion of the disc [12]. Estrogen receptor-β is expressed and localized in annulus cells of the human intervertebral disc, and 17-β-estradiol has a mitogenic effect on annulus cells of the human intervertebral disc in vitro [19]. Statins have pleiotropic effects and potential mechanisms and actions in intervertebral disc degeneration, with particular emphasis on changes in the expression of relevant molecular markers [57].

Other Considerations: Long-term follow-up of six patients with intervertebral-disc calcification in childhood revealed abnormalities in the cervical spine in four, indicating that the prognosis for long-term normal function in intervertebral-disc calcification in childhood should be more guarded than previously assumed [25]. Short-term studies demonstrate similar clinical improvements for both disk replacements and fusion procedures at up to 2-year follow-up [10].

Recovery

Light activity (weeks): Evidence does not specify a discrete week range for light activity resumption; however, nearly all patients with lesions of the lumbar intervertebral discs in older children and adolescents recover as a result of conservative treatment [3]. The prognosis for these lesions is good [3].

Full activity (months): Short-term studies demonstrate similar clinical improvements for both disk replacements and fusion procedures at up to 2-year follow-up [10]. Repetitive loading of the spine has demonstrable short-term and possibly permanent effects on the lumbar intervertebral disk [11].

Complete recovery / outcome plateau (months): Restoration of disc height and normal histology occurs by six months following chymopapain injection [26]. Long-term follow-up of six patients with intervertebral-disc calcification in childhood revealed abnormalities in the cervical spine in four, suggesting the prognosis for long-term normal function should be more guarded than previously assumed [25].

Rehabilitation protocol: The first and fundamental predictor of success in disc surgery is the selection of only patients who have the classic signs and symptoms of that disorder [4]. It should not be assumed that degenerative changes always precede disc herniation [28].

Functional milestones: MRI signal distribution indices are able to discriminate between scoliosis and spondylolisthesis and their severities [5]. These indices provide essential information on the composition and structure of the discs whatever the pathology considered [5]. Most herniations of a lumbar intervertebral disc that occur before the age of sixty years are protrusions of the nucleus pulposus [8], whereas after the age of sixty years, prolapse of the anulus fibrosus predominates in the few herniations that occur [8].

Other Considerations: Signs of early disc degeneration related to tumor treatment can be seen in the intervertebral discs of radiotherapy-treated childhood brain tumor survivors [1]. Different spinal subtypes have characteristics of lumbar disc degeneration at specific levels with age [2]. Lesions of the lumbar intervertebral discs may occur in older children and adolescents [3]. The osteogenic potential of degenerated intervertebral discs appears to increase with the severity of degeneration [12] and is greater in the tissue near the spinal canal than in tissue in the inner portion of the disc [12]. In vitro manipulation of disc cells provides an experimental window for testing how disc cells from given individuals respond when they are grown in environments which direct cells to have either spindle- or rounded-shapes [18]. Findings on estrogen receptor-β expression and localization in annulus cells provide new information on the fundamental cell biology of the disc cell [19]. The nucleus pulposus can regenerate following chymopapain injection [26]. The distance between both centers through advancing stages of degeneration demonstrated decrease of signal intensity progressing along the longitudinal axis initially [51] and along the cranio-caudal direction at later stages [51]. Matrix changes resulting from diminished flow in rabbit lumbar arteries were not progressive [58] and differed from the degenerative disc changes seen in the process of human IVD degeneration [58].

Key Evidence

  • [L3] Signs of early disc degeneration related to tumor treatment can be seen in the intervertebral discs of survivors. (10.1186/s12891-023-06509-4)
  • [L3] Different spinal subtypes have characteristics of lumbar disc degeneration at specific levels with age. (10.1186/s13018-019-1537-7)
  • [L4] Lesions of the lumbar intervertebral discs may occur in older children and adolescents; the prognosis is good, and nearly all of the patients recover as a result of conservative treatment. (10.2106/00004623-195032010-00009)
  • [L4] The results support the concept that the first and fundamental predictor of success in disc surgery is the selection of only patients who have the classic signs and symptoms of that disorder. (10.2106/00004623-198668010-00023)
  • [L4] Moreover, these indices are able to discriminate between scoliosis and spondylolisthesis and their severities, and provide essential information on the composition and structure of the discs whatever the pathology considered. (10.1186/1471-2474-13-239)
  • [L4] Anterior rupture of the disc is a rare lesion that can be identified by discography when other investigations are inconclusive; the information obtained allowed for a more effective operative approach. (10.2106/00004623-198365080-00025)
  • [L4] The technique proposed in this study showed significant differences in the distribution of the MR signal intensity within the nucleus zone of intervertebral discs due to the pathology and its severity. (10.1186/1471-2474-11-189)
  • [L4] Most herniations of a lumbar intervertebral disc that occur before the age of sixty years are protrusions of the nucleus pulposus, while after that age prolapse of the anulus fibrosus predominates in the few herniations that occur. (10.2106/00004623-199072020-00009)
  • [L4] Magnetic resonance DTI quantitative imaging provides a means to assess the biochemical composition changes within the intervertebral discs, offering valuable insights for the clinical diagnosis and evaluation of therapeutic efficacy in intervertebral disc degenerative diseases. (10.1186/s12891-025-08382-9)
  • [L5] Short-term studies demonstrate similar clinical improvements for both disk replacements and fusion procedures at up to 2-year follow-up. (10.5435/00124635-200612000-00002)
  • [L3] The T2* values suggest that repetitive loading of the spine has demonstrable short-term and possibly permanent effects on the lumbar intervertebral disk. (10.1177/23259671221088572)
  • [L4] The osteogenic potential of degenerated intervertebral discs appears to increase with the severity of degeneration and to be greater in the tissue near the spinal canal than in tissue in the inner portion of the disc. (10.1186/s12891-016-1015-x)
  • [L4] The ultrasound-guided disc pain induction test may help diagnose disc degeneration and identify culprit lesions, even when multiple discs exhibit findings of degeneration. (10.1186/s13018-023-04327-x)
  • [L4] Disc sequestration that mimics a tumor is difficult to diagnose preoperatively. (10.1186/s12891-018-2070-2)
  • [L3] The symptoms experienced by patients should be the primary concern in deciding to perform discectomy. (10.1302/0301-620x.104b6.bjj-2021-1725.r2)
  • [L2] With current techniques and in conjunction with standardized methods for assessment of pain, lumbar discography is a highly reliable and specific diagnostic test. (10.2106/00004623-199072070-00019)
  • [L4] This paper summarizes the effects of various cell death patterns on the disease progression of intervertebral disc degeneration, providing new perspectives and potential clinical intervention strategies for the prevention and treatment of IDD. (10.1186/s13018-024-05280-z)
  • [L5] In vitro manipulation of disc cells provides an experimental window for testing how disc cells from given individuals respond when they are grown in environments which direct cells to have either spindle- or rounded-shapes. (10.1186/1471-2474-1-1)
  • [L5] These findings in cells from the annulus are important because these data provide new information on the fundamental cell biology of the disc cell. (10.1186/1471-2474-3-4)
  • [L4] Discograms have yet to be proved a reliable diagnostic aid in the treatment of back, neck, or nerve-root pain. (10.2106/00004623-196850040-00007)
  • [L1] The presence of an HIZ on a lumbar MRI T2-weighted image indicates abnormal disc morphology. (10.1186/s13018-017-0523-1)
  • [L4] Chemonucleolysis is an effective and safe alternative to surgical excision of a disc for herniated nucleus pulposus in adolescents. (10.2106/00004623-198567090-00016)
  • [L1] Nevertheless, it remains a safe and effective surgical intervention for treating herniated lumbar discs in the context of obesity. (10.1186/s12891-024-07455-5)
  • [L5] The nucleus pulposus can regenerate following chymopapain injection, with restoration of disc height and normal histology by six months. (10.2106/00004623-198365090-00002)
  • [L5] The authors recommend using these media as standard for disc cell culture to harmonize preclinical study results. (10.1186/s13018-018-0914-y)
  • [L4] It should not be assumed that degenerative changes always precede disc herniation. (10.1302/0301-620x.95b8.31660)
  • [L5] Surgical defects in the disc can lead to disc collapse, fibrosis, and protrusion, but fusion is not achieved by curettage alone. (10.2106/00004623-194830030-00009)
  • [L5] The MRI protocol combined with principal component analysis and agglomerative hierarchical clustering are promising tools to classify degenerated intervertebral discs. (10.1186/1471-2474-13-195)
  • [L5] No mechanical failures were observed, even after each 30-million-cycle interval, which simulates approximately 80 years of lumbar-bending motions. (10.2106/jbjs.25.00594)
  • [L5] The study suggests that a 5 mm implant height provides biomechanical properties similar to intact specimens, whereas larger heights alter facet joint mechanics. (10.1186/s13018-020-02157-9)
  • [L5] A strict mathematical definition of the neutral zone based on spinal motion segment compliance is proposed, which is objective, conceptually correct, and does not depend on arbitrarily chosen criteria. (10.1186/1471-2474-12-38)
  • [L5] Gene therapy has shown much promise in the treatment of intervertebral disk degeneration, with many new targets and vectors being investigated. (10.5435/00124635-200806000-00003)
  • [L4] Spontaneous resorption of lumbar disk herniation is a promising avenue for non-surgical management, associated with mechanisms such as inflammation, neovascularization, and macrophage infiltration. (10.1186/s13018-025-05959-x)
  • [L5] Distraction accelerated the lengthening of the vertebrae and the heightening of the intervertebral disc, with no observable degeneration or decline in the mechanical performance of the intervertebral discs for these distraction conditions. (10.2106/jbjs.24.00224)
  • [L4] According to these promising results and MRI findings after two years follow-up, intradiscal injection of NP cells after endoscopic discectomy seems safe and could be considered as an effective therapeutic method in CLBP with no recurrence. (10.1186/s12891-025-09186-7)
  • [L4] Repeat steroid injections are a justifiable form of treatment in symptomatic patients with lumbar or cervical disc herniation whose symptoms are not satisfactorily relieved after the first injection. (10.1302/0301-620x.100b10.bjj-2018-0461.r1)
  • [L5] The computational accuracy and efficiency of in-silico study can be improved in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio. (10.1186/s13018-021-02655-4)
  • [L5] The proteoglycans of the human infant intervertebral disc share a basic structure with those of hyaline cartilage but differ in dimensions, with the nucleus pulposus containing less protein and smaller aggregates than the annulus fibrosus and cartilage end-plate. (10.2106/00004623-198567020-00016)
  • [L4] Flexion / extension is not a simple circular motion; disc prostheses need a variable center of rotation for flexion / extension below disc level with the capability to move both along the x- and the y-axis during motion, plus a second completely independent center of rotation for lateral bending above disc level to closely replicate in-vivo motion. (10.1186/s12891-022-05121-2)
  • [L5] This increased motion may increase tensile strain in a graft, potentially predisposing to non-union in lumbar arthrodesis without instrumentation. (10.2106/00004623-199412000-00012)
  • [L5] It has a low facet joint reduction rate, minimum soft tissue injury, and precisely identifies the midline of the central spinal canal. (10.1186/s13018-023-04476-z)
  • [L4] In patients where preoperative evaluation does not clearly indicate the exact level of disc herniation, the presence of the so-called jerk reflex can indicate which nerve root is being put on tension by the abnormal disc material. (10.2106/00004623-196951080-00019)
  • [L5] The PGA-HA nucleus-implants were able to restore biomechanical characteristics of spinal segments in flexion/extension, and sealing the annulus defect effectively prevented herniation of the implant. (10.1186/1749-799x-4-25)
  • [L1] A positive MRI T2-weighted image of the lumbar disc with HIZ indicates disc degeneration and may be a specific indicator for the physical diagnosis of discogenic low back pain. (10.1186/s13018-023-04187-5)
  • [L5] Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc, further promoting the regeneration and repair of intervertebral discs. (10.1186/s12891-022-05422-6)
  • [L4] Our study found that vertebral bone marrow fat is associated with sagittal spine alignment, which may serve as a new additional explanation for the association of sagittal alignment with spinal degeneration. (10.1186/s13018-023-03944-w)
  • [L3] Measurement of TK with T2 on standing whole spinal radiographs resulted in a greater measurement error of up to 6.6°. (10.1186/s12891-021-04786-5)
  • [L4] The distance between both centers through advancing stages of degeneration demonstrated decrease of signal intensity progressing along the longitudinal axis initially and then along the cranio-caudal direction at later stages. (10.1186/s12891-017-1838-0)
  • [L3] The 4-grade fat infiltration system was seen to be more effective than the 3-grade fat infiltration system in the determination of the level of fat infiltration in the paraspinal muscles and the prediction of lumbar disc herniation. (10.1186/s12891-022-05180-5)
  • [L5] There is a great unmet need for regenerative solutions that not only treat symptoms but also reverse or halt the progression of intervertebral disc degeneration. (10.1016/j.arthro.2023.10.032)
  • [L4] New quantitative MRI sequences such as T2 mapping, T1ρ mapping, and MR spectroscopy can evaluate anatomical and physiological changes of intervertebral disc degeneration in more detail than conventional T2WI, but the values obtained still do not directly correlate with low back pain, necessitating more widespread use of techniques specific to clinical symptoms. (10.3390/diagnostics12030707)
  • [L5] This degeneration and rupture takes place without change in the nucleus pulposus. (10.2106/00004623-195234010-00012)
  • [L4] This review summarizes the pleiotropic effects of statins and explores their potential mechanisms and actions in intervertebral disc degeneration, with particular emphasis on changes in the expression of relevant molecular markers. (10.1186/s13018-025-05487-8)
  • [L5] These matrix changes, however, were not progressive and differed from the degenerative disc changes seen in the process of human IVD degeneration. (10.1186/s12891-019-2721-y)

See Also

References

[1] Early disc degeneration in radiotherapy-treated childhood brain tumor survivors. BMC Musculoskeletal Disorders. 2023. DOI: 10.1186/s12891-023-06509-4

[2] Different spinal subtypes with varying characteristics of lumbar disc degeneration at specific level with age: a study based on an asymptomatic population. Journal of Orthopaedic Surgery and Research. 2020. DOI: 10.1186/s13018-019-1537-7

[3] INTERVERTEBRAL-DISC LESIONS IN CHILDREN AND ADOLESCENTS. The Journal of Bone & Joint Surgery. 1950. DOI: 10.2106/00004623-195032010-00009

[4] The ruptured intervertebral disc. Follow-up report on the first case fifty years after recognition of the syndrome and its surgical significance.. The Journal of Bone & Joint Surgery. 1986. DOI: 10.2106/00004623-198668010-00023

[5] MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis. BMC Musculoskeletal Disorders. 2012. DOI: 10.1186/1471-2474-13-239

[6] Anterior rupture of the lumbosacral disc. Report of a case.. The Journal of Bone & Joint Surgery. 1983. DOI: 10.2106/00004623-198365080-00025

[7] Effect of pathology type and severity on the distribution of MRI signal intensities within the degenerated nucleus pulposus: application to idiopathic scoliosis and spondylolisthesis. BMC Musculoskeletal Disorders. 2010. DOI: 10.1186/1471-2474-11-189

[8] Histological changes in aging lumbar intervertebral discs. Their role in protrusions and prolapses.. The Journal of Bone & Joint Surgery. 1990. DOI: 10.2106/00004623-199072020-00009

[9] Exploring the correlation between magnetic resonance diffusion tensor imaging (DTI) parameters and aquaporin expression and biochemical composition content in degenerative intervertebral disc nucleus pulposus tissue: a clinical experimental study. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08382-9

[10] Total Disk Arthroplasty. Journal of the American Academy of Orthopaedic Surgeons. 2006. DOI: 10.5435/00124635-200612000-00002

[11] Patterns of Intervertebral Disk Alteration in Asymptomatic Elite Rowers: A T2 MRI Mapping Study. Orthopaedic Journal of Sports Medicine*. 2022. DOI: 10.1177/23259671221088572

[12] Differences in calcification and osteogenic potential of herniated discs according to the severity of degeneration based on Pfirrmann grade: a cross-sectional study. BMC Musculoskeletal Disorders. 2016. DOI: 10.1186/s12891-016-1015-x

[13] Ultrasound-guided disc pain induction test for diagnosis of discogenic lumbar pain: a cross-sectional study. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-04327-x

[14] Two cases in which 3D MRI was used to differentiate between a disc mass that mimics a tumor and neurinoma. BMC Musculoskeletal Disorders. 2018. DOI: 10.1186/s12891-018-2070-2

[15] No correlation identified between the proportional size of a prolapsed intravertebral disc with disability or leg pain. The Bone & Joint Journal. 2022. DOI: 10.1302/0301-620x.104b6.bjj-2021-1725.r2

[16] Lumbar discography in normal subjects. A controlled, prospective study.. The Journal of Bone & Joint Surgery. 1990. DOI: 10.2106/00004623-199072070-00019

[17] Exploration and breakthrough in the mode of intervertebral disc cell death may lead to significant advances in treatments for intervertebral disc degeneration. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-05280-z

[18] Human disc cells in monolayer vs 3D culture: cell shape, division and matrix formation. BMC Musculoskeletal Disorders. 2000. DOI: 10.1186/1471-2474-1-1

[19] Expression and localization of estrogen receptor-β in annulus cells of the human intervertebral disc and the mitogenic effect of 17-β-estradiol in vitro. BMC Musculoskeletal Disorders. 2002. DOI: 10.1186/1471-2474-3-4

[20] The Question of Lumbar Discography. The Journal of Bone & Joint Surgery. 1968. DOI: 10.2106/00004623-196850040-00007

[21] The correlation between the high-intensity zone on a T2-weighted MRI and positive outcomes of discography: a meta-analysis. Journal of Orthopaedic Surgery and Research. 2017. DOI: 10.1186/s13018-017-0523-1

[22] Narrowing of the intervertebral-disc space in children. Presumably an infectious lesion of the disc.. The Journal of bone and joint surgery. American volume. 1960.

[23] Chemonucleolysis for herniated nucleus pulposus in adolescents.. The Journal of Bone & Joint Surgery. 1985. DOI: 10.2106/00004623-198567090-00016

[24] Comparative outcomes of obese and non-obese patients with lumbar disc herniation receiving full endoscopic transforaminal discectomy: a systematic review and meta-analysis. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07455-5

[25] Intervertebral-Disc Calcification in Childhood: A DISTINCT CLINICAL SYNDROME.. The Journal of Bone and Joint Surgery. American Volume. 1964.

[26] Chymopapain, chemonucleolysis, and nucleus pulposus regeneration.. The Journal of Bone & Joint Surgery. 1983. DOI: 10.2106/00004623-198365090-00002

[27] Standardisation of basal medium for reproducible culture of human annulus fibrosus and nucleus pulposus cells. Journal of Orthopaedic Surgery and Research. 2018. DOI: 10.1186/s13018-018-0914-y

[28] Do intervertebral discs degenerate before they herniate, or after?. The Bone & Joint Journal. 2013. DOI: 10.1302/0301-620x.95b8.31660

[29] EXPERIMENTAL INTERVERTEBRAL-DISC LESIONS. The Journal of Bone & Joint Surgery. 1948. DOI: 10.2106/00004623-194830030-00009

[30] Assessment of mechanical properties of isolated bovine intervertebral discs from multi-parametric magnetic resonance imaging. BMC Musculoskeletal Disorders. 2012. DOI: 10.1186/1471-2474-13-195

[31] Comparative in Vitro Analysis of Wear Particles Generated by a Viscoelastic Disc Versus 2 Articulating Total Disc Replacements. Journal of Bone and Joint Surgery. 2025. DOI: 10.2106/jbjs.25.00594

[32] The impact of different artificial disc heights during total cervical disc replacement: an in vitro biomechanical study. Journal of Orthopaedic Surgery and Research. 2021. DOI: 10.1186/s13018-020-02157-9

[33] Quantifying intervertebral disc mechanics: a new definition of the neutral zone. BMC Musculoskeletal Disorders. 2011. DOI: 10.1186/1471-2474-12-38

[34] Gene Therapy for the Treatment of Degenerative Disk Disease. Journal of the American Academy of Orthopaedic Surgeons. 2008. DOI: 10.5435/00124635-200806000-00003

[35] Mechanisms and management of self-resolving lumbar disc herniation: bridging molecular pathways to non-surgical clinical success. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05959-x

[36] Effects of Sustained Tensile Distraction on Vertebrae and Intervertebral Disc Growth. Journal of Bone and Joint Surgery. 2025. DOI: 10.2106/jbjs.24.00224

[37] Safety of autologous nucleus pulposus cell transplantation with fibrin glue following endoscopic discectomy in chronic low back pain: a preliminary phase I trial. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09186-7

[38] Chapter 12 Physical Examination of the Spine. 2019.

[39] Repeat epidural steroid injections for radicular pain due to lumbar or cervical disc herniation. The Bone & Joint Journal. 2018. DOI: 10.1302/0301-620x.100b10.bjj-2018-0461.r1

[40] Disc measurement and nucleus calibration in a smoothened lumbar model increases the accuracy and efficiency of in-silico study. Journal of Orthopaedic Surgery and Research. 2021. DOI: 10.1186/s13018-021-02655-4

[41] Proteoglycans of human infant intervertebral disc. Electron microscopic and biochemical studies.. The Journal of Bone & Joint Surgery. 1985. DOI: 10.2106/00004623-198567020-00016

[42] Cervical disc prostheses need a variable center of rotation for flexion / extension below disc level, plus a separate COR for lateral bending above disc level to more closely replicate in-vivo motion: MRI-based biomechanical in-vivo study. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05121-2

[43] Increase of motion between lumbar vertebrae after excision of the capsule and cartilage of the facets. A cadaver study.. The Journal of Bone & Joint Surgery. 1994. DOI: 10.2106/00004623-199412000-00012

[44] Finite element mechanical analysis of ipsilateral approach and contralateral approach in unilateral bilateral endoscopic spine surgery. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-04476-z

[45] A Diagnostic Sign in Fourth and Fifth Lumbar Disc Surgery. The Journal of Bone & Joint Surgery. 1969. DOI: 10.2106/00004623-196951080-00019

[46] Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy. Journal of Orthopaedic Surgery and Research. 2009. DOI: 10.1186/1749-799x-4-25

[47] The correlation between the lumbar disc MRI high-intensity zone and discogenic low back pain: a systematic review and meta-analysis. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-04187-5

[48] Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05422-6

[49] Associations between vertebral bone marrow fat and sagittal spine alignment as assessed by chemical shift-encoding-based water–fat MRI. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-03944-w

[50] Determining the validity and reliability of spinopelvic parameters through comparing standing whole spinal radiographs and upright computed tomography images. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04786-5

[51] Spatial geometric and magnetic resonance signal intensity changes with advancing stages of nucleus pulposus degeneration. BMC Musculoskeletal Disorders. 2017. DOI: 10.1186/s12891-017-1838-0

[52] An evaluation of the efficacy of a four-grade fat infiltration classification method, presented for the first time in literature. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05180-5

[53] Biological Therapeutic Modalities for Intervertebral Disc Diseases: An Orthoregeneration Network (ON) Foundation Review. Arthroscopy. 2023. DOI: 10.1016/j.arthro.2023.10.032

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[58] Effect of diminished flow in rabbit lumbar arteries on intervertebral disc matrix changes using MRI T2-mapping and histology. BMC Musculoskeletal Disorders. 2019. DOI: 10.1186/s12891-019-2721-y

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