- Email: [email protected]
Intervertebral disc “dysgeneration”
The Spine Journal 15 (2015) 1915–1918
Perspective
Intervertebral disc ‘‘dysgeneration’’ Keith D.K. Luk, MCh(Orth), FRCSE, FRCSG, FRACS, FHKAM(Orth)*, Dino Samartzis, DSc* Department of Orthopaedics & Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong, SAR, China Received 13 July 2014; accepted 28 July 2014
In a recent study by Vos et al. [1], low back pain (LBP) was noted to be the world’s most disabling condition and a global burden. An etiological factor related to the development of LBP has been intervertebral disc degeneration [2–5]. Disc degeneration occurs in all age groups and populations [2,4]. Numerous risk factors have been proposed to be associated with the development of disc degeneration, such as age progression, abnormal biomechanics, lifestyle/environmental factors, and genetics [4,6–27]. In fact, because of the clinical relevance of disc degeneration, astronomical sums of funding have been spent globally on various research platforms to assess this entity. Disc degeneration has been traditionally assessed by T2-weighted magnetic resonance imaging (MRI), which essentially assesses the water content based on the ‘‘signal intensity’’ [28,29]. The intervertebral disc comprises two main regions: an inner gelatinous core (nucleus pulposus) and an outer layer (annulus fibrosus) [30]. These structures are rich in collagen and macromolecules, such as proteoglycans, and contain an abundance of water in normal states. It has been believed that as the disc degenerates, it loses proteoglycan and water content. As such, a loss of water content by the disc would be noted as a loss of signal intensity on MRI, resulting in a ‘‘black disc.’’ This ‘‘black disc’’ has been regarded throughout the past three decades since the advent of MRI as a disc that has ‘‘degenerated.’’ In other words, the disc was at one time well hydrated and ‘‘normal,’’ but because of a series of events, water content FDA device/drug status: Not applicable. Author disclosures: KDKL: Endowments: Tam Sai Kit endowment Professorship (E US per annum, Paid directly to institution). DS: Grants: RGC Hong Kong AOSpine (F). The disclosure key can be found on the Table of Contents and at www. TheSpineJournalOnline.com. Disclosures: The authors have no financial or competing interests to disclose in relation to this work. * Corresponding author. Department of Orthopaedics & Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong, SAR, China. Tel.: (852) 2255-4813; fax: (852) 2817-4392. E-mail address: [email protected] (K.D.K. Luk) or dsamartzis@ msn.com (D. Samartzis) http://dx.doi.org/10.1016/j.spinee.2014.07.020 1529-9430/Ó 2015 Elsevier Inc. All rights reserved.
was lost and various macromolecules were broken down leading to morphologic and biochemical alterations of the disc that would lead to ‘‘degenerated’’ changes. Such changes can cause the disc to develop fissures in its outer annulus fibrosus, whereby nerve fibers can migrate in the disc and become irritated by proinflammatory cytokines associated with the degenerative process or its adjacent end plate may alter causing irritation of the surrounding nerve fibers [31–34]. This degenerative process, in time, may lead to ‘‘secondary structural changes’’ of the disc, characterized as disc height loss, disc displacement (eg, bulging, protrusion, herniation, sequestration), and annular tears in the disc or the formation of high-intensity zones [35,36]. Moreover, the degenerative process alters the stress/strain applied on the vertebral motion segment and modifies its kinematics, resulting in additional secondary structural changes such as osteophyte or bone spur formations and/ or adjacent level vertebral bone marrow changes (ie, Modic changes) (Figure, Left) [36–38]. It has been commonly propagated in the literature and clinical practice that a ‘‘black disc’’ on an MRI is a degenerated entity. It is this particular phenotype that many have included in their classification schemes of degeneration on MRI and oftentimes used to denote ‘‘cases’’ in numerous association studies addressing genetics or pain profiles [9]. However, what is often noted on an MRI, does not always represent the disc’s degenerative process on histology [39]. Furthermore, numerous studies have been in direct conflict in finding associations between disc degeneration (ie, black disc) to that of LBP [40–42]. Many investigators have suggested that disc degeneration is not always synonymous with LBP, and there could be individuals with severe disc degeneration but no history of pain [40,41]. Studies have also noted that MRI findings of degenerative changes have no predictive utility of future LBP development [41,43]. Such studies further raise the notion that the conventionally used classification schemes of disc degeneration or the phenotyping may need to be revamped to address clinically relevant or true entities of degenerative findings. Genetic studies using this phenotype of a black disc are difficult to replicate between groups or find
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K.D.K. Luk and D. Samartzis / The Spine Journal 15 (2015) 1915–1918
Figure. T2-weighted sagittal MRIs of the lower thoracic and lumbar spine. (Left) L3–S1 disc degeneration with disc displacement, disc space narrowing, and osteophyte formations. Modic changes are also noted at the L5–S1 disc level. (Right) Disc dysgeneration at T9–T10 and T12–L1, with disc space narrowing but no secondary changes. Note the normal discs throughout the lumbar region. Arrows denote low signal intensity of the discs on MRI, manifesting as a black disc.
significant genetic factors related to disc ‘‘degeneration’’ [9]. In fact, studies have also noted that disc degeneration on MRI may manifest as skipped level patterns (21% of multilevel disc degeneration cases) throughout the lumbar spine [44]. In other words, it has been commonly thought that disc degeneration occurs at a single level, predominantly at the lower lumbar region, and any new discs that degenerate occur consecutively in the adjacent levels. However, skipped patterns of disc degeneration, whereby healthy discs are located in between these degenerated discs, challenge the traditional dogma of how degenerative discs occur in the lumbar spine [44–46]. In line with this, studies have also noted that ‘‘black discs’’ are common in adolescents, which contradicts the traditional notion of wear-and-tear of the disc brought upon by aging and subsequent processes [4,47]. Such findings in the young could in fact have been preexistent in the life-span. Furthermore, although mechanical injury may play a role [25], this may not always be definitive. Therefore, all the above studies and observations question the notion of what is in fact a ‘‘degenerated’’ disc on
MRI. Are all black discs ‘‘degenerated’’? Should we generalize all black discs the same or should we compartmentalize them based on their etiological origins and clinical relevance? We propose that there could be spinal discs that were never well hydrated from the onset. As such, these discs were not normal or never reached their full potential of hydration, manifesting as ‘‘black discs’’ on MRI; thereby, theoretically, they could not be considered as a structure that has ‘‘degenerated.’’ Such discs may represent a subgroup of individuals that may have disc ‘‘dysgeneration,’’ a condition brought on by development, whereby an individual’s disc was never fully developed or hydrated to the extent to manifest as normal on MRI (Figure, Right). Therefore, such individuals may not undergo the typical morphologic and biochemical changes within the disc, which may usher a cascade of events that would lead to discogenic or painful discs. Such a subgroup of individuals may explain the disconnect between studies addressing the association or predictive capacity of disc degeneration on MRI and LBP, as well as identifying and replicating genetic factors related
K.D.K. Luk and D. Samartzis / The Spine Journal 15 (2015) 1915–1918
to degeneration. Spinal discs that are ‘‘dysgenerated’’ may also explain why some discs appear degenerated on MRI with perhaps disc space narrowing but do not exhibit any of the other secondary structural changes as previously noted. Such structural changes only manifest when a disc truly degenerates and deviates from its normal state. In fact, unique morphologic changes of the adjacent vertebral end plate to the disc that have a developmental origin have been observed and largely remain clinically benign [48]. Therefore, such a notion as a ‘‘dysgenerated’’ disc is not far-fetched. Future studies of disc degeneration should be more cognizant about the phenotyping of disc degeneration and what is regarded as truly ‘‘degenerated.’’ Having a deeper understanding of disc biology and its development is essential to understand the natural history of the disc and its role as a pain generator. Future classification schemes and prospective studies of disc degeneration in the setting of risk factors and even in the association of LBP should aim to distinguish which discs naturally degenerate to those that were never fully developed or ‘‘dysgenerated.’’ Acknowledgments This work was supported by grants from the Hong Kong Theme-Based Research Scheme (T12-708/12N) and the International Society for the Study of the Lumbar Spine MacNab/LaRocca Award. References [1] Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2163–96. [2] Cheung KM, Karppinen J, Chan D, Ho DW, Song YQ, Sham P, et al. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine 2009;34:934–40. [3] Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A. Low back pain in relation to lumbar disc degeneration. Spine 2000;25:487–92. [4] Samartzis D, Karppinen J, Mok F, Fong DY, Luk KD, Cheung KM. A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status. J Bone Joint Surg Am 2011;93:662–70. [5] Takatalo J, Karppinen J, Niinimaki J, Taimela S, Nayha S, Mutanen P, et al. Does lumbar disc degeneration on magnetic resonance imaging associate with low back symptom severity in young Finnish adults? Spine 2011;36:2180–9. [6] Battie MC, Videman T, Kaprio J, Gibbons LE, Gill K, Manninen H, et al. The Twin Spine Study: contributions to a changing view of disc degeneration. Spine J 2009;9:47–59. [7] Battie MC, Videman T, Levalahti E, Gill K, Kaprio J. Genetic and environmental effects on disc degeneration by phenotype and spinal level: a multivariate twin study. Spine 2008;33:2801–8. [8] Eskola PJ, Kjaer P, Daavittila IM, Solovieva S, Okuloff A, Sorensen JS, et al. Genetic risk factors of disc degeneration among 12-14-year-old Danish children: a population study. Int J Mol Epidemiol Genet 2010;1:158–65.
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[9] Eskola PJ, Lemmela S, Kjaer P, Solovieva S, Mannikko M, Tommerup N, et al. Genetic association studies in lumbar disc degeneration: a systematic review. PLoS One 2012;7:e49995. [10] Eskola PJ, Mannikko M, Samartzis D, Karppinen J. Genome-wide association studies of lumbar disc degeneration–are we there yet? Spine J 2014;14:479–82. [11] Kao PY, Chan D, Samartzis D, Sham PC, Song YQ. Genetics of lumbar disk degeneration: technology, study designs, and risk factors. Orthop Clin North Am 2011;42:479–86. vii. [12] Song YQ, Karasugi T, Cheung KM, Chiba K, Ho DW, Miyake A, et al. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J Clin Invest 2013;123:4909–17. [13] Videman T, Battie MC, Ripatti S, Gill K, Manninen H, Kaprio J. Determinants of the progression in lumbar degeneration: a 5-year follow-up study of adult male monozygotic twins. Spine 2006;31: 671–8. [14] Williams FM, Bansal AT, van Meurs JB, Bell JT, Meulenbelt I, Suri P, et al. Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects. Ann Rheum Dis 2013;72:1141–8. [15] Williams FM, Popham M, Sambrook PN, Jones AF, Spector TD, MacGregor AJ. Progression of lumbar disc degeneration over a decade: a heritability study. Ann Rheum Dis 2011;70:1203–7. [16] Cheung KM, Chan D, Karppinen J, Chen Y, Jim JJ, Yip SP, et al. Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine 2006;31: 1143–8. [17] Jim JJ, Noponen-Hietala N, Cheung KM, Ott J, Karppinen J, Sahraravand A, et al. The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration. Spine 2005;30:2735–42. [18] Sambrook PN, MacGregor AJ, Spector TD. Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 1999;42:366–72. [19] Samartzis D, Karppinen J, Cheung JP, Lotz J. Disk degeneration and low back pain: are they fat-related conditions? Global Spine J 2013;3: 133–44. [20] Samartzis D, Karppinen J, Chan D, Luk KD, Cheung KM. The association of lumbar intervertebral disc degeneration on magnetic resonance imaging with body mass index in overweight and obese adults: a population-based study. Arthritis Rheum 2012;64: 1488–96. [21] Takatalo J, Karppinen J, Taimela S, Niinimaki J, Laitinen J, Sequeiros RB, et al. Association of abdominal obesity with lumbar disc degeneration–a magnetic resonance imaging study. PLoS One 2013;8:e56244. [22] Leino-Arjas P, Kauppila L, Kaila-Kangas L, Shiri R, Heistaro S, Heliovaara M. Serum lipids in relation to sciatica among Finns. Atherosclerosis 2008;197:43–9. [23] Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between smoking and low back pain: a meta-analysis. Am J Med 2010;123:87.e7–87.e35. [24] Adams MA, Freeman BJ, Morrison HP, Nelson IW, Dolan P. Mechanical initiation of intervertebral disc degeneration. Spine 2000;25:1625–36. [25] Adams MA, Lama P, Zehra U, Dolan P. Why do some intervertebral discs degenerate, when others (in the same spine) do not? Clinical Anat 2014. [Epub ahead of print]. [26] Stefanakis M, Luo J, Pollintine P, Dolan P, Adams MA. ISSLS Prize Winner: Mechanical influences in progressive intervertebral disc degeneration. Spine 2014;39:1365–72. [27] Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine 2004;29:2700–9. [28] Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 2001;26:1873–8.
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[29] Schneiderman G, Flannigan B, Kingston S, Thomas J, Dillin WH, Watkins RG. Magnetic resonance imaging in the diagnosis of disc degeneration: correlation with discography. Spine 1987;12: 276–81. [30] Chan WC, Sze KL, Samartzis D, Leung VY, Chan D. Structure and biology of the intervertebral disk in health and disease. Orthop Clin North Am 2011;42:447–64. vii. [31] Adams M, Dolan P, Hutton W. The stages of disc degeneration as revealed by discograms. J Bone Joint Surg Br 1986;68-B:36–41. [32] Adams MA, Dolan P. Intervertebral disc degeneration: evidence for two distinct phenotypes. J Anat 2012;221:497–506. [33] Adams MA, McNally DS, Dolan P. ’Stress’ distributions inside intervertebral discs. The effects of age and degeneration. J Bone Joint Surg Br 1996;78:965–72. [34] Ohtori S, Inoue G, Miyagi M, Takahashi K. Pathomechanisms of discogenic low back pain in humans and animal models. Spine J 2014. [35] Aprill C, Bogduk N. High-intensity zone: a diagnostic sign of painful lumbar disc on magnetic resonance imaging. Br J Radiol 1992;65: 361–9. [36] Pye SR, Reid DM, Lunt M, Adams JE, Silman AJ, O’Neill TW. Lumbar disc degeneration: association between osteophytes, endplate sclerosis and disc space narrowing. Ann Rheum Dis 2007;66: 330–3. [37] Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 1988;166:193–9. [38] Takatalo J, Karppinen J, Niinimaki J, Taimela S, Mutanen P, Sequeiros RB, et al. Association of modic changes, Schmorl’s nodes, spondylolytic defects, high-intensity zone lesions, disc herniations, and radial tears with low back symptom severity among young Finnish adults. Spine 2012;37:1231–9.
[39] Quint U, Wilke HJ. Grading of degenerative disk disease and functional impairment: imaging versus patho-anatomical findings. Eur Spine J 2008;17:1705–13. [40] Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW. Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am 1990;72: 403–8. [41] Borenstein DG, O’Mara JW Jr, Boden SD, Lauerman WC, Jacobson A, Platenberg C, et al. The value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects : a seven-year follow-up study. J Bone Joint Surg Am 2001;83-A:1306–11. [42] Chou D, Samartzis D, Bellabarba C, Patel A, Luk KD, Kisser JM, et al. Degenerative magnetic resonance imaging changes in patients with chronic low back pain: a systematic review. Spine 2011;36:S43–53. [43] Steffens D, Hancock MJ, Maher CG, Williams C, Jensen TS, Latimer J. Does magnetic resonance imaging predict future low back pain? A systematic review. Eur J Pain 2014;18:755–65. [44] Cheung KM, Samartzis D, Karppinen J, Mok FP, Ho DW, Fong DY, et al. Intervertebral disc degeneration: new insights based on ‘‘skipped’’ level disc pathology. Arthritis Rheum 2010;62:2392–400. [45] Cheung KM, Samartzis D, Karppinen J, Luk KD. Are ‘‘patterns’’ of lumbar disc degeneration associated with low back pain?: new insights based on skipped level disc pathology. Spine 2012;37:E430–8. [46] Hsu K, Zucherman J, Shea W, Kaiser J, White A, Schofferman J, et al. High lumbar disc degeneration. Incidence and etiology. Spine 1990;15:679–82. [47] Heithoff KB, Gundry CR, Burton CV, Winter RB. Juvenile discogenic disease. Spine 1994;19:335–40. [48] Saluja G, Fitzpatrick K, Bruce M, Cross J. Schmorl’s nodes (intravertebral herniations of intervertebral disc tissue) in two historic British populations. J Anat 1986;145:87–96.
Perspective
Intervertebral disc ‘‘dysgeneration’’ Keith D.K. Luk, MCh(Orth), FRCSE, FRCSG, FRACS, FHKAM(Orth)*, Dino Samartzis, DSc* Department of Orthopaedics & Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong, SAR, China Received 13 July 2014; accepted 28 July 2014
In a recent study by Vos et al. [1], low back pain (LBP) was noted to be the world’s most disabling condition and a global burden. An etiological factor related to the development of LBP has been intervertebral disc degeneration [2–5]. Disc degeneration occurs in all age groups and populations [2,4]. Numerous risk factors have been proposed to be associated with the development of disc degeneration, such as age progression, abnormal biomechanics, lifestyle/environmental factors, and genetics [4,6–27]. In fact, because of the clinical relevance of disc degeneration, astronomical sums of funding have been spent globally on various research platforms to assess this entity. Disc degeneration has been traditionally assessed by T2-weighted magnetic resonance imaging (MRI), which essentially assesses the water content based on the ‘‘signal intensity’’ [28,29]. The intervertebral disc comprises two main regions: an inner gelatinous core (nucleus pulposus) and an outer layer (annulus fibrosus) [30]. These structures are rich in collagen and macromolecules, such as proteoglycans, and contain an abundance of water in normal states. It has been believed that as the disc degenerates, it loses proteoglycan and water content. As such, a loss of water content by the disc would be noted as a loss of signal intensity on MRI, resulting in a ‘‘black disc.’’ This ‘‘black disc’’ has been regarded throughout the past three decades since the advent of MRI as a disc that has ‘‘degenerated.’’ In other words, the disc was at one time well hydrated and ‘‘normal,’’ but because of a series of events, water content FDA device/drug status: Not applicable. Author disclosures: KDKL: Endowments: Tam Sai Kit endowment Professorship (E US per annum, Paid directly to institution). DS: Grants: RGC Hong Kong AOSpine (F). The disclosure key can be found on the Table of Contents and at www. TheSpineJournalOnline.com. Disclosures: The authors have no financial or competing interests to disclose in relation to this work. * Corresponding author. Department of Orthopaedics & Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Rd, Pokfulam, Hong Kong, SAR, China. Tel.: (852) 2255-4813; fax: (852) 2817-4392. E-mail address: [email protected] (K.D.K. Luk) or dsamartzis@ msn.com (D. Samartzis) http://dx.doi.org/10.1016/j.spinee.2014.07.020 1529-9430/Ó 2015 Elsevier Inc. All rights reserved.
was lost and various macromolecules were broken down leading to morphologic and biochemical alterations of the disc that would lead to ‘‘degenerated’’ changes. Such changes can cause the disc to develop fissures in its outer annulus fibrosus, whereby nerve fibers can migrate in the disc and become irritated by proinflammatory cytokines associated with the degenerative process or its adjacent end plate may alter causing irritation of the surrounding nerve fibers [31–34]. This degenerative process, in time, may lead to ‘‘secondary structural changes’’ of the disc, characterized as disc height loss, disc displacement (eg, bulging, protrusion, herniation, sequestration), and annular tears in the disc or the formation of high-intensity zones [35,36]. Moreover, the degenerative process alters the stress/strain applied on the vertebral motion segment and modifies its kinematics, resulting in additional secondary structural changes such as osteophyte or bone spur formations and/ or adjacent level vertebral bone marrow changes (ie, Modic changes) (Figure, Left) [36–38]. It has been commonly propagated in the literature and clinical practice that a ‘‘black disc’’ on an MRI is a degenerated entity. It is this particular phenotype that many have included in their classification schemes of degeneration on MRI and oftentimes used to denote ‘‘cases’’ in numerous association studies addressing genetics or pain profiles [9]. However, what is often noted on an MRI, does not always represent the disc’s degenerative process on histology [39]. Furthermore, numerous studies have been in direct conflict in finding associations between disc degeneration (ie, black disc) to that of LBP [40–42]. Many investigators have suggested that disc degeneration is not always synonymous with LBP, and there could be individuals with severe disc degeneration but no history of pain [40,41]. Studies have also noted that MRI findings of degenerative changes have no predictive utility of future LBP development [41,43]. Such studies further raise the notion that the conventionally used classification schemes of disc degeneration or the phenotyping may need to be revamped to address clinically relevant or true entities of degenerative findings. Genetic studies using this phenotype of a black disc are difficult to replicate between groups or find
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K.D.K. Luk and D. Samartzis / The Spine Journal 15 (2015) 1915–1918
Figure. T2-weighted sagittal MRIs of the lower thoracic and lumbar spine. (Left) L3–S1 disc degeneration with disc displacement, disc space narrowing, and osteophyte formations. Modic changes are also noted at the L5–S1 disc level. (Right) Disc dysgeneration at T9–T10 and T12–L1, with disc space narrowing but no secondary changes. Note the normal discs throughout the lumbar region. Arrows denote low signal intensity of the discs on MRI, manifesting as a black disc.
significant genetic factors related to disc ‘‘degeneration’’ [9]. In fact, studies have also noted that disc degeneration on MRI may manifest as skipped level patterns (21% of multilevel disc degeneration cases) throughout the lumbar spine [44]. In other words, it has been commonly thought that disc degeneration occurs at a single level, predominantly at the lower lumbar region, and any new discs that degenerate occur consecutively in the adjacent levels. However, skipped patterns of disc degeneration, whereby healthy discs are located in between these degenerated discs, challenge the traditional dogma of how degenerative discs occur in the lumbar spine [44–46]. In line with this, studies have also noted that ‘‘black discs’’ are common in adolescents, which contradicts the traditional notion of wear-and-tear of the disc brought upon by aging and subsequent processes [4,47]. Such findings in the young could in fact have been preexistent in the life-span. Furthermore, although mechanical injury may play a role [25], this may not always be definitive. Therefore, all the above studies and observations question the notion of what is in fact a ‘‘degenerated’’ disc on
MRI. Are all black discs ‘‘degenerated’’? Should we generalize all black discs the same or should we compartmentalize them based on their etiological origins and clinical relevance? We propose that there could be spinal discs that were never well hydrated from the onset. As such, these discs were not normal or never reached their full potential of hydration, manifesting as ‘‘black discs’’ on MRI; thereby, theoretically, they could not be considered as a structure that has ‘‘degenerated.’’ Such discs may represent a subgroup of individuals that may have disc ‘‘dysgeneration,’’ a condition brought on by development, whereby an individual’s disc was never fully developed or hydrated to the extent to manifest as normal on MRI (Figure, Right). Therefore, such individuals may not undergo the typical morphologic and biochemical changes within the disc, which may usher a cascade of events that would lead to discogenic or painful discs. Such a subgroup of individuals may explain the disconnect between studies addressing the association or predictive capacity of disc degeneration on MRI and LBP, as well as identifying and replicating genetic factors related
K.D.K. Luk and D. Samartzis / The Spine Journal 15 (2015) 1915–1918
to degeneration. Spinal discs that are ‘‘dysgenerated’’ may also explain why some discs appear degenerated on MRI with perhaps disc space narrowing but do not exhibit any of the other secondary structural changes as previously noted. Such structural changes only manifest when a disc truly degenerates and deviates from its normal state. In fact, unique morphologic changes of the adjacent vertebral end plate to the disc that have a developmental origin have been observed and largely remain clinically benign [48]. Therefore, such a notion as a ‘‘dysgenerated’’ disc is not far-fetched. Future studies of disc degeneration should be more cognizant about the phenotyping of disc degeneration and what is regarded as truly ‘‘degenerated.’’ Having a deeper understanding of disc biology and its development is essential to understand the natural history of the disc and its role as a pain generator. Future classification schemes and prospective studies of disc degeneration in the setting of risk factors and even in the association of LBP should aim to distinguish which discs naturally degenerate to those that were never fully developed or ‘‘dysgenerated.’’ Acknowledgments This work was supported by grants from the Hong Kong Theme-Based Research Scheme (T12-708/12N) and the International Society for the Study of the Lumbar Spine MacNab/LaRocca Award. References [1] Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2163–96. [2] Cheung KM, Karppinen J, Chan D, Ho DW, Song YQ, Sham P, et al. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine 2009;34:934–40. [3] Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A. Low back pain in relation to lumbar disc degeneration. Spine 2000;25:487–92. [4] Samartzis D, Karppinen J, Mok F, Fong DY, Luk KD, Cheung KM. A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status. J Bone Joint Surg Am 2011;93:662–70. [5] Takatalo J, Karppinen J, Niinimaki J, Taimela S, Nayha S, Mutanen P, et al. Does lumbar disc degeneration on magnetic resonance imaging associate with low back symptom severity in young Finnish adults? Spine 2011;36:2180–9. [6] Battie MC, Videman T, Kaprio J, Gibbons LE, Gill K, Manninen H, et al. The Twin Spine Study: contributions to a changing view of disc degeneration. Spine J 2009;9:47–59. [7] Battie MC, Videman T, Levalahti E, Gill K, Kaprio J. Genetic and environmental effects on disc degeneration by phenotype and spinal level: a multivariate twin study. Spine 2008;33:2801–8. [8] Eskola PJ, Kjaer P, Daavittila IM, Solovieva S, Okuloff A, Sorensen JS, et al. Genetic risk factors of disc degeneration among 12-14-year-old Danish children: a population study. Int J Mol Epidemiol Genet 2010;1:158–65.
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