Genetics, Lifestyle, Environmental Factors

International Publicized Data

GMCD Instructional  Course Lectures

Author :  

Dr. med. Guy M.C. Declerck MD (GMCD)

Medical FRCS-, FRCS Ed Orth-, M Ch Orth-, PhD-studies

Spinal Surgical and Research Fellow, Perth, Western Australia

Spinal Orthopaedic Surgeon and Surgical Instructor

Consultant R&D Innovative & Restorative Spinal Technologies

President International Association of Andullation Technology (IAAT)

Copywriter / Translator:   Filip Vanhaecke PhD

Illustrative expertise & page layout:   Lennart Benoot, Mincko, Halle, Flanders, Belgium

Review scientific literature:   Medical Consulting Advice, Ostend, Flanders, Belgium

Support:   International Association of Andullation Therapy (IAAT)

Legal advice:   Anthony De Zutter,

Dedication to the Colombian Family Gloria Rúa Meneses and her sons Andres David and Juan Camilo Hinestroza, both members of the National Colombian Waterpolo Team. For their friendship and hospitality. August 2014.


Relying on the work of giants is the lifeblood of scientific research. Indeed, if I have seen further, it is by standing on the shoulders of giants. One might even say that I have always depended on the kindness of strangers in this regard (*).

The continuous support by professor BA Kakulas (Neuropathology), professor JR Taylor (Spinal Anatomy and Human Biology), and Sir George M Bedbrook (Spinal Orthopaedic and Rehabilitation Surgeon) made it possible to analyse 27539 post-mortem human spines, normal and pathological, in the Department of Neuropathology, Royal Perth Hospital/University Western Australia, Perth.

Note: in order not to disturb easy reading of the underneath scientifically based chapters, only a few authors are mentioned in the text where dr. Guy considered it essential. Their names are placed between brackets. Further information on their individual research can be read in the last chapter ‘Literature Encyclopedia’.

(*) Mirsky Steve. Technology is making it harder for word thieves to earn outrageous fortunes.Scientific American, February 2014, p. 64


1. Aging processes, genetic factors, and physical activities

2. Aging processes and routine daily activities

3. Combined genetic-mechanic influences

4. Combination of genetic and environmental factors

5. Influence of unfavorable, abnormal, or aberrant genes

6. Upper versus lower lumbar degenerative changes

7. Socioeconomic lifestyle factors

8. Influence of traumatic accidents

9. Repetitive heavy and physically demanding jobs

10. Literature Encyclopaedia

1. Aging processes, genetic factors, physical activities

All tissues, including the intervertebral discs (IVD), will age. The aging processes occur at the same time in all IVDs and are irreversible. But aging is not synonymous with degeneration.

It is known since a long time that familial heredity, which includes genetic factors, plays a substantial role in the development of major degenerative changes and lesions in the IVDs. The presence or absence of a certain genetic inheritance determines who will develop the intradiscal degenerative cascade and when. But on their own, abnormal genes will not generate degenerative processes in all IVDs at the same time and in the same proportion.

Although the genetic influence is the same in all IVDs of a particular human spinal column, some repetitive daily and lifetime physical environmental factors are essential to trigger the development of degenerative structural features. However, each IVD is influenced differently by the performed physical activities. In other words, the characteristics of each activity finally will determine which intradiscal levels become more affected. Repetitive daily routine activities including mechanical spinal loading factors during sitting, standing and walking differ from the influence of repetitive daily, heavy physical and spinal overloading activities (Fig. 1a and 1b).

Fig. 1a. A90/139. Although the genetic influence for developing degenerative changes is identical for all lumbar intervertebral discs (IVD), the degenerative intradiscal cascade evolves differently in each of these discs depending on the characteristics of routine daily activities. In this 50 year old male, heavy labourer, the aging processes are responsible for the typical brown colour in the nucleus pulposus at the L3-4 IVD. The L4-5 IVD presents the typical degenerative signs: disc height loss with fragmented nucleus pulposus, ruptures of the endplate and the annulus fibrosus. An anterior ‘herniating’ pathway is present as well. At the L5-S1 IVD level the posterior annulus is ruptured with subsequent protrusion and disc height loss. Inflammatory reactions compatible with the MRI Modic signs are visible at L4-L5 and L5-S1 (subchondral intraosseous light brown discoloration).

Left: Declerck / Kakulas, Neuropathology, Perth, Western Australia

Right: Detailed artistic illustration by the Colombian sculptor Alonso Ríos Vanegas -

Fig. 1b. X90/1437. Male, 63 years old. Osteoporotic L5 vertebral body and sacrum. The L4-5 IVD displays normal aging processes with swelling pressure in the still hydrophilic nucleus which reflects the ‘aging’ brown colour due to the accumulation of metabolic catabolic products. Degenerative annular and endplate lesions are not present in the L4-5 IVD. The L5-S1 IVD shows degenerative features: an asymmetrical posterior disc height narrowing, a large posterior internal disc tear with protruding nuclear tissue through a degenerated and ruptured annulus.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

2. Aging processes and routine daily activities

Intervertebral disc aging is not similar to disc degeneration. While the daily mechanical influences of activities continue, all IVDs undergo extensive aging changes as a consequence of

(1) declined nutrition of the IVD through the endplates,

(2) suicidal apoptotic cellular processes,

(3) cell cluster formation,

(4) cell necrosis,

(5) increasing number of senescent cells, and

(6) degradation of major molecules in the extracellular matrix, the proteoglycans and collagens.

Aging processes result in dehydration and desiccation of the nucleus pulposus. Signs of IVD aging can be seen on magnetic resonance images (MRI): loss of signal intensity, ‘dark’ disc, annular bulging, high intensity zones as a result of incomplete radial in-to-out developing annular fissures, and vertebral rim osteophytes. These aging signs in the intervertebral disc are no similar to disc degeneration.

3. Combined genetic-mechanic influences

In the presence of unfavorable genes, the daily routine mechanical loading patterns on the intervertebral discs accelerate the aging processes in these discs. This genetic-mechanic combination finally remains the major causative factor for the formation of degenerative lesions routinely seen at autopsy (Fig. 1a and 1b) and on magnetic resonance images (MRI) as well. The degenerative damage typically includes endplate fissures and defects, complete in-to-out radial annular tears, important disappearance of nuclear material due to the resorbing inflammatory processes, and loss of nuclear and annular height. All these lesions eventually lead to the destruction and dysfunction of the IVD and may potentially result in the degenerative discogenic syndrome (DDS).

4. Combination of genetic and environmental factors

Except for spinal traumata which cause direct accidental and incidental lesions to the IVDs, ruptures of the endplates, internal destruction of the nuclei, and tears in the annuli are determined by the combination of genetic, mechanical, and environmental factors.

A few facts are scientifically proven. Structural degenerative IVD changes are not seen in some ethnic groups when their individuals life in identical circumstances. Disc degeneration is more commonly found in men and women who already developed arthritis in other synovial joints (hips, knees, shoulders, etc …). The L4-5 and L5-S1 IVDs consistently exhibit more degenerative intradiscal and annular changes than the L1-2 and L2-3 lumbar IVDs. Degenerative discogenic lesions are more routinely seen from the fourth decade on. Lumbar discs of twins show similar aging and degenerative findings on MRI whatever their professional activities. These findings underline a complex interplay between genetic,  mechanical and environmental factors.

5. Unfavorable, abnormal, or aberrant genes

The presence of unfavorable genes influences the development of degenerative processes in the IVDs. The aberrant genes code for synthesis of abnormal proteins, proteoglycans, collagens, proteinases and cytokines. Higher concentrations of aberrant molecules alter the structural and functional properties of the extracellular matrices and may lead to the development of degenerative lesions in the endplates, annuli and nuclei.

In animals, typical examples of these genetically based phenomena occur in the IVDs of the so-called chondrodystrophoid dogs (the dachshund and the basset hound dogs with short limbs).

In humans, it is suggested that approximately 70 % to 75 % of all individuals contain abnormal genes which induce degenerative changes in the extracellular matrix of disc cells. Aberrant vitamin D receptor genes (VDR) impair the sulfation of the chondroitin and keratan chains and build abnormal proteoglycans (PGs). No longer able to retain the normal amount of water molecules, the changed VDR-genes are responsible for decreased MRI intensity signals of the IVD. Variants of the collagen IX gene (= COL9A2 and COL9A3 genes) produce unstable type IX collagens which no longer are able to stabilize the type II collagens. The presence of these genes leads to aberrations in the endplate, nucleus and inner annulus. Variants of the aggrecan gene construct abnormal types of the most important proteoglycan. Variants of the matrix metalloproteinase genes (MMP genes) accelerate the degenerative processes in the elderly. Abnormal collagen type I genes (COL1A1 gene) interfere in the production of the type I collagens which are important for the annular resistance of the annulus to tension forces. Abnormal genes for coding interleukin-1 and interleukin-6 stimulate the function of these pro-inflammatory cytokine molecules.

6. Upper versus lower lumbar degenerative lesions

The individuals who carry some or all of the disadvantageous genes will weaken the integrity of the extracellular matrix of the lumbar IVDs more extensively and earlier than ‘intact’ individuals. However, the lumbar IVDs react differently to the impact of the environmental and mechanical loading factors. Postmortem investigations indicate different degenerative IVD patterns at the upper and lower IVD levels. The upper lumbar IVDs exhibit rather degenerative endplate defects at the L1-L2 and L2-3 levels while the lower lumbar IVDs display rather degenerative annular tears at the L4-5 and L5-S1 levels (Declerck).

7. Socioeconomic lifestyle factors

The contribution of a variety of socioeconomic lifestyle factors to IVD degeneration is clearly controversial and overestimated. These factors may determine which spinal levels become affected but not in which individual.

There is no evidence or insufficient evidence that lifestyle factors such as eating, drinking, sports, sedentary activity, work, smoking, obesity and drugs may induce the degenerative intradiscal processes.

Strangely enough, identical physical activities are considered to be harmful when performed during professional duties while they are propagated to be beneficial during the exertion of sports.

There is no evidence or insufficient evidence that the presence or absence of physical factors such as physical fitness, mobility, flexibility and muscle strength lead to IVD degeneration.

Atherosclerosis is only thought to be a risk of discogenic degeneration but has never been proven.

There is no consistent evidence that wearing school bags initiates degeneration of IVDs and that all kind of furniture will prevent these processes. Other unknown and underlying factors make the difference.

There is no evidence at all that psychosocial factors such as happiness, health perspective, well-being, parental support, tiredness, anger, violence, disobedience and so on result in degeneration of the IVD.

8. Influence of traumatic accidents

Accidental spinal injuries with vertebral fractures and dislocations are a frequent reason for developing chronic low back pain in the long term. Once these spinal conditions have been completely restored or healed, the usually non-diagnosed but associated traumatic ruptures in the endplates and annuli develop into full-blown degenerative lesions (Fig. 8a and 8b).


Fig. 8a. A90/139, man, 62-year old. He suffered chronic undulating and disabling thoracolumbar pains. All radiological investigations showed a healed minimal anterior vertebral body (VB) T11 fracture. He was considered a lunatic, crazy, psychologically disturbed and of course a compensation seeking person. Postmortem analysis ordered by the coroner showed a clearly healed fracture of the T11 VB. At the T10-T11 intervertebral disc level, the typical ‘aging’ brown colour is evident. A small intradiscal lesion in the nucleus above the inferior but intact endplate is visible (any significance?). However, at the T11-T12 IVD level, a large anteroposterior internal disc rupture is documented as well as disrupted superior endplate lesions with an anterior inflammatory subchondral osseous reaction and, more posteriorly, the formation of an intraosseous nuclear protrusion (not yet a Schmorl nodule) in T11 VB.

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)


Fig. 8b. Female, 53 years. ‘Chance’ type fracture of the T11 vertebral body (VB). The postmortem image shows the healed VB following postoperative (Knodt rod) fixation. The complete detachment of the T12 VB from its proximal T11-T12 disc junction and the ruptured superior endplate of T12 were never diagnosed radiologically. Internal T11-T12 intervertebral disc degeneration (necrosis?) is evident

(Declerck / Kakulas, Neuropathology, Perth, Western Australia)

9. Repetitive heavy and physically demanding jobs

People with repetitive, heavy and physically demanding jobs leading to abnormal load torsion (manual lifting) and whole-body vibration (truck driving), no doubt, experience unfavourable distribution and transmission of mechanical stresses on their IVDs. Then, it seems logical that their IVDs may develop more severe signs of degeneration. However, this is not a correct statement and not at all an universal phenomenon. Most heavy labourers simply have no more but no less degenerative discogenic signs than those who have sedentary jobs (sitting). Annular bulging is closely associated with heavy lifting but not at all with other spinal degenerative features.

Although such professional exposures may certainly lead to the development of degenerative lesions in the endplate and in the annulus leading to chronic low back pain, there exists no directly related evidence between these heavy loading activities and the origin nor the evolution of these visible degenerating disc signs – at least on magnetic resonance imaging (MRI).

A clear relationship between heavy physical loading activities and degeneration of the discs has never been shown. If their discs showed evidence of degenerative tears in the endplates and/or in the annuli, weightlifters would be unable to lift their Olympic weights.

Although important and significant degenerative structural defects in the lumbar disc may occur as a consequence of repetitive bending, twisting, fatigue loading and heavy physical work, they are more frequently the result of a sedentary environment that implies hypomobility. Studies on monozygotic twins demonstrate that the additional effects of heavy physical loading patterns only contribute for a small portion to the development, the presence and the degree of disc degeneration.

10. Literature Encyclopaedia


Adams MA, Dolan P

Could sudden increases in physical activity cause degeneration of intervertebral discs?

The Lancet, 1997, 350:734

Adams MA, Hutton WC

The effect of fatigue on the lumbar intervertebral disc

J Bone Joint Surg, 1983, 65B:199

Ala-Kokko L

Genetic risk factors for lumbar disc disease

Ann Med, 2002, 34:42

Andersson GBJ

The epidemiology of spinal disorders

In: The Adult Spine. Principles and Practice

Frymoyer JW, ed., Raven Press, 1991:107

Annunen S, Paassilta P, Lohiniva J, Perälä M, Pihlajamaa T, Karppinen J, Tervonen O, Kröger H, Lähde S, Vanharanta H, Ryhänen L,

Göring HHH, Ott J, Prockop DJ, Ala-Kokko L

An allele of COL9A2 associated with intervertebral disc disease

Science, 1999, 285:409


Battié MC, Haynor DR, Fisher LD, Gill K, Gibbons LE, Videman T        

Similarities in degenerative findings on magnetic resonance images of the lumbar spines of identical twins

J Bone Joint Surg, 1995, 77A:1662

Battié MC, Videman T

Lumbar disc degeneration. Epidemiology and genetics

J Bone Joint Surg, 2006, 88A:3

Battié MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K

1995 Volvo award in clinical sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins

Spine, 1995, 20:2601

Battié MC, Videman T, Gibbons LE, Manninen H, Gill K, Pope M, Kaprio J

Occupational driving and lumbar disc degeneration. A case-control study

The Lancet, 2002, 360:1369

Battié MC, Videman T, Gill K, Moneta GB, Nyman R, Kaprio J, Koskenvuo M

1991 Volvo award in clinical sciences. Smoking and lumbar intervertebral disc degeneration. An MRI study of identical twins

Spine, 1991, 16:1015

Battié MC, Videman T, Levälahti 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

Battié MC, Videman T, Levälahti E, Gill K, Kaprio J

Heritability of low back pain and the role of disc degeneration

Pain, 2007, 131:272

Battié MC, Videman T, Parent E        

Lumbar disc degeneration. Epidemiology and genetic influences

Spine, 2004, 29:2679

Bhardwaj R, Midha R

Synchronous lumbar disc herniation in adult twins. Case report

Can J Neurol Sci, 2004, 31:554

Bray JP, Burbidge HM

The canine intervertebral disk. Part Two. Degenerative changes--nonchondrodystrophoid versus chondrodystrophoid disks

J Am Anim Hosp Assoc, 1998, 34:135

Burns JW, Loecker TH, Fischer JR Jr, Bauer DH

Prevalence and significance of spinal disc abnormalities in an asymptomatic acceleration subject panel

Aviat Space Environ Med, 1996, 67:849

Burton AK, Balagué F, Cardon G, Eriksen HR, Henrotin Y, Lahad A, Leclerc A, Müller G, van der Beek AJ; COST B13 working group on

guidelines for prevention in low back pain

Chapter 2. European guidelines for prevention in low back pain. November 2004

Eur Spine J, 2006, 15(Suppl 2):S136


Caplan PS, Freedman LM, Connelly TP

Degenerative joint disease of the lumbar spine in coal miners. A clinical and x-ray study

Arthritis Rheum, 1966, 9:693

Chan D, Song Y, Sham P, Cheung KM

Genetics of disc degeneration

Eur Spine J, 2006, 15(Suppl 3):S317

Cheung KM, Chan D, Karppinen J, Chen Y, Jim JJ, Yip SP, Ott J, Wong KK, Sham P, Luk KD, Cheah KS, Leong JC, Song YQ

Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese

Spine, 2006, 31:1143

Cong L, Pang H, Xuan D, Tu GJ

Association between the expression of aggrecan and the distribution of aggrecan gene variable number of tandem repeats with symptomatic lumbar disc herniation in Chinese Han of Northern China

Spine, 2010, 35:1371

Cs-Szabo G, Ragasa-San Juan D, Turumella V, Masuda K, Thonar EJ, An HS

Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during

intervertebral disc degeneration

Spine, 2002, 27:2212


Declerck GMC

‘Neuropathologic spinal anatomy of all cervical, thoracic and lumbar intervertebral discs in 23.539 consecutive sagittal vertebral autopsies in different types of pathologies. A continuous observation during 50 years’

Observations made at the Department of Neuropathology, University of  Western Australia

In cooperation with the professors BA Kakulas & JR Taylor and Sir George M. Bedbrook

Serial publications on the website

Doege KJ, Coulter SN, Meek LM, Maslen K, Wood JG

A human-specific polymorphism in the coding region of the aggrecan gene. Variable number of tandem repeats produce a range of core protein sizes in the general population

J Biol Chem, 1997, 272:13974

Dong DM, Yao M, Liu B, Sun CY, Jiang YQ, Wang YS

Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults

Eur Spine J, 2007, 16:1958


Elfering A, Semmer N, Birkhofer D, Zanetti M, Hodler J, Boos N

Young investigator award 2001 winner. Risk factors for lumbar disc degeneration. A 5-year prospective MRI study in asymptomatic individuals

Spine, 2002, 27:125

Eyre DR, Matsui Y, WU JJ

Collagen polymorphisms of the intervertebral disc

Biochem Soc Trans, 2002, 30:844


Fang Y, van Meurs JB, d'Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA,

Uitterlinden AG

Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture. The Rotterdam study

Am J Hum Genet, 2005, 77:807

Farfan HF        The torsional injury of the lumbar spine

Spine, 1984, 9:53

Feng H, Danfelter M, Strömqvist B, Heinegård D

Extracellular matrix in disc degeneration

J Bone Joint Surg, 2006, 88A(Suppl 1):25

Fernandes I, Hampson G, Cahours X, Morin P, Coureau C, Couette S, Prie D, Biber J, Murer H, Friedlander G, Silve C

Abnormal sulfate metabolism in vitamin D-deficient rats

J Clin Invest, 1997, 100:2196

Findlay G, Burton K, Adams M, Dolan P, Greenough Ch, Main Ch, Coles C, Balagué F,  Bjarke ChF, James FB, Teli M

Spine Course 2006. Chronic Low Back Pain. Spine Society of Europe

Barcelona, Spain, September 2006

Friberg S, Hirsch C

Anatomical and clinical studies on lumbar disc degeneration

Acta Orthop Scand, 1949, 19:222

Frymoyer JW

Lumbar disk disease. Epidemiology

Instr Course Lect, 1992, 41:217

Frymoyer JW, Newberg A, Pope MH, Wilder DG, Clements J, MacPherson B

Spine radiographs in patients with low-back pain. An epidemiological study in men

J Bone Joint Surg, 1984, 66A:1048


Ghosh P, Taylor TK, Braund KG, Larsen LH

A comparative chemical and histochemical study of the chondrodystrophoid and nonchondrodystrophoid canine

intervertebral disc

Vet Pathol, 1976, 13:414


Hassett G, Hart DJ, Manek NJ, Doyle DV, Spector TD

Risk factors for progression of lumbar spine disc degeneration. The Chingford study

Arthr Rheum, 2003, 48:3112

Hestbaek L, Iachine IA, Leboeuf-Yde C, Kyvik KO, Manniche C

Heredity of low back pain in a young population. A classical twin study

Twin Research, 2004,7:16

Hirsch C  Studies on the pathology of low back pain

J Bone Joint Surg, 1959, 41B:237


Jim JJ, Noponen-Hietala N, Cheung KM, Ott J, Karppinen J, Sahraravand A, Luk KD, Yip SP, Sham PC, Song YQ, Leong

JC, Cheah KS, Ala-Kokko L, Chan D

The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration

Spine, 2005, 30:2735


Kales SN, Linos A, Chatzis C, Sai Y, Halla M, Nasioulas G, Christiani DC

The role of collagen IX tryptophan polymorphisms in symptomatic intervertebral disc disease in Southern European patients

Spine, 2004, 29:1266

Kawaguchi Y, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T

The association of lumbar disc disease with vitamin-D receptor gene polymorphism

J Bone Joint Surg, 2002, 84A:2022

Kawaguchi Y, Osada R, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T

Association between an aggrecan gene polymorphism and lumbar disc degeneration

Spine, 1999, 24:2456

Kelsey JL, Githens PB, O'Conner T, Weil U, Calogero JA, Holford TR, White AA 3rd, Walter SD, Ostfeld AM,

Southwick WO

Acute prolapsed lumbar intervertebral disc. An epidemiologic study with special reference to driving automobiles and cigarette smoking

Spine, 1984, 9:608

Kelsey JL, Githens PB, White AA 3rd, Holford TR, Walter SD, O'Connor T, Ostfeld AM, Weil U, Southwick WO,

Calogero JA

An epidemiologic study of lifting and twisting on the job and risk for acute prolapsed lumbar intervertebral disc

J Orthop Res, 1984, 2:61

Kelsey JL, White AA 3rd

Epidemiology and impact of low-back pain

Spine, 1980, 5:133

Kerttula LI, Serlo WS, Tervonen OA, Pääkkö EL, Vanharanta HV

Post-traumatic findings of the spine after earlier vertebral fracture in young patients. Clinical and MRI study

Spine, 2000, 25:1104

Kimura T, Nakata K, Tsumaki N, Miyamoto S, Matsui Y, Ebara S, Ochi T

Progressive degeneration of articular cartilage and intervertebral discs. An experimental study in transgenic mice bearing a type IX collagen mutation

Int Orthop, 1996, 20:177


Lawrence JS, Molyneux MK, Dingwall-Fordyce I

Rheumatism in foundry workers

Br J Ind Med, 1966, 23:42


MacGregor AJ, Andrew T, Sambrook PN, Spector TD

Structural, psychological, and genetic influences on low back and neck pain. A study of adult female twins

Arthritis Rheum, 2004, 51:160

Mannion AF, Elfering A, Staerkle R, Junge A, Grob D, Semmer NK, Jacobshagen N, Dvorak J, Boos N

Outcome assessment in low back pain: how low can you go? 

Europ Spine J, 2005, 14:1014

Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H

Familial predisposition for lumbar degenerative disc disease. A case–control study

Spine, 1998, 23:1029

Miller JA, Schmatz C, Schultz AB

Lumbar disc degeneration. Correlation with age, sex, and spine level in 600 autopsy specimens

Spine, 1988, 13:173


Noponen-Hietala N, Kyllonen E, Mannikko M, Ilkko E, Karppinen J, Ott J, and Ala-Kokko L

Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis

Ann Rheum Dis, 2003, 62:1208

Noponen-Hietala N, Virtanen I, Karttunen R, Schwenke S, Jakkula E, Li H, Merikivi R, Barral S, Ott J, Karppinen J, Ala-Kokko L

Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica

Pain, 2005, 114:186


Paassilta P, Lohiniva J, Göring HH, Perälä M, Räinä SS, Karppinen J, Hakala M, Palm T, Kröger H, Kaitila I,

Vanharanta H, Ott J, Ala-Kokko L

Identification of a novel common genetic risk factor for lumbar disk disease

J Amer Med Assoc, 2001, 285:1843

Persikov AV, Ramshaw JA, Brodsky B

Collagen model peptides. Sequence dependence of triple-helix stability

Biopolymers, 2000, 55:436

Pluijm SM, van Essen HW, Bravenboer N, Uitterlinden AG, Smit JH, Pols HA, Lips P

Collagen type I alpha1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women

Ann Rheum Dis, 2004, 63:71

Postacchini F, Roberto L, Orsola P

Familial predisposition to discogenic low-back pain. An epidemiologic and immunogenetic study

Spine, 1988, 13:1403


Richardson JK, Chung T, Schultz JS, Hurvitz E

A familial predisposition toward lumbar disc injury

Spine,1997, 22:1487

Ross JS, Masaryk TJ, Schrader M, Gentili A, Bohlman H, Modic MT

MR imaging of the postoperative lumbar spine. Assessment with gadopentetate dimeglumine

Am J Neuroradiol, 1990, 11:771

Rossignol M, Lortie M, Ledoux E

Comparison of spinal health indicators in predicting spinal status in a 1-year longitudinal study

Spine, 1993, 18:54

Roughley P, Martens D, Rantakokko J, Alini M, Mwale F, Antoniou J

The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage

Eur Cell Mater, 2006, 11:1

Roughley PJ

Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix

Spine, 2004, 29:2691

Roughley PJ, Alini M, Antoniou J

The role of proteoglycans in aging, degeneration and repair of the intervertebral disc

Biochem Soc Trans, 2002, 30:869


Sahlman J, Inkinen R, Hirvonen T, Lammi MJ, Lammi PE, Nieminen J, Lapveteläinen T, Prockop DJ, Arita M, Li SW, Hyttinen MM,

Helminen HJ, Puustjärvi K

Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen

Spine, 2001, 26:2558

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

Savage RA, Whitehouse GH, Roberts N

The relationship between the magnetic resonance imaging appearance of the lumbar spine and low back pain, age and occupation in males

Eur Spine J, 1997, 6:106

Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M,

Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S

A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease

Nat Genet, 2005, 37:607

Semba K, Araki K, Li Z, Matsumoto KI, Suzuki M, Nakagata N, Takagi K, Takeya M, Yoshinobu K, Araki M, Imai K, Abe K, Yamamura KI

A novel murine gene, sickle tail, linked to the Danforth's short tail locus, is required for normal development of the intervertebral disc

Genetics, 2006, 172:445

Skrzypiec D, Tarala M, Pollintine P, Dolan P, Adams MA

When are intervertebral discs stronger than their adjacent vertebrae?

Spine, 2007, 32:2455

Solovieva S, Kouhia S, Leino-Arjas P, Ala-Kokko L, Luoma K, Raininko R, Saarela J, Riihimäki H

Interleukin 1 polymorphisms and intervertebral disc degeneration

Epidemiology, 2004, 15:626

Solovieva S, Lohiniva J, Leino-Arjas P, Raininko R, Luoma K, Ala-Kokko L, Riihimäki H

COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine. Evidence of gene–environment interaction

Spine, 2002, 27:2691

Solovieva S, Lohiniva J, Leino-Arjas P, Raininko R, Luoma K, Ala-Kokko L, Riihimäki H

Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms

Eur Spine J, 2006, 15(5):613

Solovieva S, Noponen N, Männikkö M, Leino-Arjas P, Luoma K, Raininko R, Ala-Kokko L, Riihimäki H

Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration

Spine, 2007, 32:1700

Stokes IAF, Iatridis JC

Mechanical conditions that accelerate intervertebral disc degeneration. Overload versus immobilization

Spine, 2004, 29:2724


Takahashi M, Haro H, Wakabayashi Y, Kawa-uchi T, Komori H, Shinomiya K

The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene

J Bone Joint Surg, 2001, 83B:491

Tilkeridis C, Bei T, Garantziotis S, Stratakis CA

Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits

J Med Genet, 2005, 42:e44


Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP

Genetics and biology of vitamin D receptor polymorphisms

Gene, 2004, 338:143


Valdes AM, Hassett G, Hart DJ, Spector TD

Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes. A candidate SNP association study in the Chingford cohort

Spine, 2005, 30:2445

Videman T, Battié MC, Gibbons LE, Manninen H, Gill K, Fisher LD, Koskenvuo M

Lifetime exercise and disk degeneration. An MRI study of monozygotic twins

Med Sci Sports Exerc, 1997, 29:1350

Videman T, Battié MC, Gill K, Manninen H, Gibbons LE, Fisher LD

Magnetic resonance imaging findings and their relationships in the thoracic and lumbar spine. Insights into the etiopathogenesis of spinal degeneration

Spine, 1995, 20:928

Videman T, Battié 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

Videman T, Gibbons LE, Battié MC, Maravilla K, Vanninen E, Leppävuori J, Kaprio J, Peltonen L

The relative roles of intragenic polymorphisms of the vitamin D receptor gene in lumbar spine degeneration and bone density

Spine, 2001, 26:E7

Videman T, Leppävuori J, Kaprio J, Battié MC, Gibbons LE, Peltonen L, Koskenvuo M        

1998 Volvo award winner in basic science studies. Intragenic polymorphisms of the vitamin D receptor gene

associated with intervertebral disc degeneration

Spine, 1998, 23:2477

Videman T, Levälahti E, Battié MC

The effects of anthropometrics, lifting strength, and physical activities in disc degeneration

Spine, 2007, 32:1406

Videman T, Nurminen M

The occurrence of anular tears and their relation to lifetime back pain history. A cadaveric study using barium

sulfate discography

Spine, 2004, 29:2668

Videman T, Saarela J, Kaprio J, Näkki A, Levälahti E, Gill K, Peltonen L, Battié MC

Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing

Arthritis Rheum, 2009, 60:470

Videman T, Sarna S, Battié MC, Koskinen S, Gill K, Paananen H, Gibbons L

The long-term effects of physical loading and exercise lifestyles on back-related symptoms, disability, and

spinal pathology among men

Spine, 1995, 20:699

Virtanen IM, Karppinen J, Taimela S, Ott J, Barral S, Kaikkonen K, Heikkilä O, Mutanen P, Noponen N, Männikkö M,

Tervonen O, Natri A, Ala-Kokko L

Occupational and genetic risk factors associated with intervertebral disc disease

Spine, 2007, 32:1129

Virtanen IM, Noponen N, Barral S, Karpinen J, Li H, Vuoristo M, Niinimäki J, Ott J, Ala-Kokko L, Männikkö M

Putative susceptibility locus on chromosome 21q for lumbar disc disease (LDD) in the Finnish population

J Bone Miner Res, 2007, 22:701

Virtanen IM, Song YQ, Cheung KM, Ala-Kokko L, Karppinen J, Ho DW, Luk KD, Yip SP, Leong JC, Cheah KS, Sham P, Chan D

Phenotypic and population differences in the association between CILP and lumbar disc disease

J Med Genet, 2007, 44:285


Weiler C, Schietzsch M, Kirchner T, Nerlich AG, Boos N, Wuertz K

Age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong intra-individual correlation

Eur Spine J, 2012, 21(Suppl 6):S810

Williams FM, Kato BS, Livshits G, Sambrook PN, Spector TD, MacGregor AJ

Lumbar disc disease shows linkage to chromosome 19 overlapping with a QTL for hand OA

Ann Rheum Dis, 2008, 67:117

Wrocklage C, Wassmann H, Paulus W

COL9A2 allelotypes in intervertebral disc disease

Biochem Biophys Res Commun, 2000, 279:398


Ye S, Watts GF, Mandalia S, Humphries SE, Henney AM

Preliminary report. Genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis

Brit Heart J, 1995, 73:209