Mechanical loading influences the lumbar intervertebral disc. A cross-sectional study in 308 athletes and 71 controls

36. Owen PJ, Hangai M, Kaneoka K, Rantalainen T, Belavy DL. Mechanical loading influences the lumbar intervertebral disc. A cross-sectional study in 308 athletes and 71 controls. J Orthop Res [Internet]. 2020 [cited 2020 Jul 22];n/a(n/a).

Mechanical loading influences the lumbar intervertebral disc. A cross-sectional study in 308 athletes and 71 controls Patrick J Owen 1, Mika Hangai 2, Koji Kaneoka 3, Timo Rantalainen 1 4, Daniel L Belavy 1

Free article

Abstract

There is evidence in animal populations that loading and exercise can positively impact the intervertebral disc (IVD). However, there is a paucity of information in humans.

We examined the lumbar IVDs in 308 young athletes across six sporting groups (baseball, swimming, basketball, kendo, soccer, and running; mean age 19 years) and 71 nonathletic controls. IVD status was quantified via the ratio of IVD to vertebral body height (IVD hypertrophy) and ratio of signal intensity in the nucleus to that in the annulus signal (IVD nucleus hydration) on sagittal T2-weighted magnetic resonance imaging. P values were adjusted via the false discovery rate method to mitigate false positives.

In examining the whole collective, compared to referents, there was evidence of IVD hypertrophy in basketball (P ≤ .029), swimming (P ≤ .010), soccer (P = .036), and baseball (P = .011) with greater IVD nucleus hydration in soccer (P = .007). After matching participants based on back-pain status and body height, basketball players showed evidence of IVD hypertrophy (P ≤ .043) and soccer players greater IVD nucleus hydration (P = .001) than referents. Greater career duration and training volume correlated with less (ie, worse) IVD nucleus hydration, but explained less than 1% of the variance in this parameter. In this young collective, increasing age was associated with increased IVD height. The findings suggest that basketball and soccer may be associated with beneficial adaptations in the IVDs in young athletes. In line with evidence on other tissues, such as muscle and bone, the current study adds to evidence that specific loading types may beneficially modulate lumbar IVD properties.

37. Mitchell UH, Bowden JA, Larson RE, Belavy DL, Owen PJ. Long-term running in middle-aged men and intervertebral disc health, a cross-sectional pilot study. PLOS ONE. 2020 Feb 21;15(2):e0229457.

Long-term running in middle-aged men and intervertebral disc health, a cross-sectional pilot study

Ulrike H Mitchell 1, Jennifer A Bowden 1, Robert E Larson 1, Daniel L Belavy 2, Patrick J Owen 2

Abstract

Purpose: To measure intervertebral disc (IVD) health parameters in middle-aged long-term runners compared to matched non-physically active controls.

Methods: Seventeen males aged 44-62yr were included in the study: 9 runners with a running history of >10yr, averaging >50km/week, and eight matched non-physically active controls, the data from one participant had to be excluded. T2-relaxometry, diffusion weighted imaging, T1- and T2-weighted MR scanning, as well as T2 time mapping were performed. Morphological data relating to IVD were extrapolated.

Results: Compared to controls on average, runners had 20% greater IVD height (p = 0.002) and seven percentage points greater IVD-vertebral body height ratio (p = 0.001). No significant differences were observed between groups for mean(SD) IVD hydration status, as indicated by similar T2-times (runners: 94.4(11.1)ms, controls: 88.6(23.6)ms), or apparent diffusion coefficients (runners: 249.0(175.2)mm2/s, controls: 202.3(149.5)mm2/s). Average Pfirrmann score for the L5-S1 IVD was 2.2(0.7) for runners and 3.3(1.0) for controls (p = 0.026), average scores for all lumbar levels (L2-S1) were 1.9(0.2) and 2.5(0.7), respectively (p = 0.036). Anterior annulus T2-time and overall average lumbar level Pfirrmann grades were strongly correlated (r = 0.787, p = 0.021 and r = -0.704, p = 0.034, respectively) with greater distances run per week. Average lumbar level Pfirrmann grades were also strongly correlated (r = -0.823, p = 0.006) to total years of running.

Conclusion: Middle-aged long-term endurance runners exhibit less age-related decline in their lumbar IVDs. In addition, the measures of IVD morphology appeared to be better in those who had been running for a greater number of years, as well as in those who ran a greater distance per week.

38. Belavý DL, Quittner MJ, Ridgers N, Ling Y, Connell D, Rantalainen T. Running exercise strengthens the intervertebral disc. Sci Rep. 2017 Apr 19;7(1):45975.

Running exercise strengthens the intervertebral disc

Abstract

There is currently no evidence that the intervertebral discs (IVDs) can respond positively to exercise in humans. Some authors have argued that IVD metabolism in humans is too slow to respond anabolically to exercise within the human lifespan. Here we show that chronic running exercise in men and women is associated with better IVD composition (hydration and proteoglycan content) and with IVD hypertrophy. Via quantitative assessment of physical activity we further find that accelerations at fast walking and slow running (2 m/s), but not high-impact tasks, lower intensity walking or static positions, correlated to positive IVD characteristics. These findings represent the first evidence in humans that exercise can be beneficial for the IVD and provide support for the notion that specific exercise protocols may improve IVD material properties in the spine. We anticipate that our findings will be a starting point to better define exercise protocols and physical activity profiles for IVD anabolism in humans.

-----------------------------------------------------------------

39. Shapiro IM, Risbud MV, editors. The Intervertebral Disc: Molecular and Structural Studies of the Disc in Health and Disease [Internet]. Vienna: Springer Vienna; 2014 [cited 2020 Jul 27].

About this book The intervertebral disc is a complex structure that separates opposing vertebrae, permits a wide range of motion, and accommodates high biomechanical forces. Disc degeneration leads to a loss of function and is often associated with excruciating pain.

Written by leading scientists and clinicians, the first part of the book provides a review of the basic biology of the disc in health and disease. The second part considers strategies to mitigate the effects of disc degeneration and discusses the possibility of engineering replacement tissues. The final section is devoted to approaches to model normal development and elucidate the pathogenesis of degenerative disc disease using animal, organ and cell culture techniques.

The book bridges the gap between the basic and clinical sciences; the target audience includes basic scientists, orthopaedists and neurologists, while at the same time appealing to the needs of graduate students, medical students, interns and fellows.

----------------------

Tom Goom RunningPhysio by email: 22.10.2024: Hello Adri

Low back pain is now the leading cause of disability worldwide (Hartvigsen et al. 2018). It can have a long lasting effects on people’s lives, mental wellbeing and goal activities.

For many years avoidance of exercise was suggested. I qualified at a time when bed rest was still recommended! Spines were considered fragile and running was thought to be damaging.

Fortunately thinking has evolved and research has far more encouraging findings including 3 key points that we’ll expand on in this newsletter:

⦁ Pain free pathology is common and doesn’t usually worsen with running

⦁ Running can improve spine health

⦁ A run-walk programme can be effective in treating persistent low back pain

Let’s start by discussing ‘pathology’ in pain free runners. I use the quotation marks there as there’s some debate over whether it is considered ‘pathology’ when there’s no pain. Horga et al. (2022) found that over 60% of asymptomatic runners had disc degeneration on MRI and these findings didn’t worsen despite training for and completing a marathon:

Maselli et al. (2020) reported that the prevalence of LBP may be lower in runners compared to the general population. Belavy et al. (2017) found that running may actually strengthen the intervertebral discs (IVD) of the lumbar spine, a finding supported by Mitchell et al. (2020) who reported better spine health in runners compared to non-runners:

These are positive findings that running may be beneficial rather than harmful for the spine but can it actually treat low back pain? A new study has tested this with a randomised controlled trial (Neason et al. 2024). Here’s a summary of their research:

Important exclusion criteria

The authors mention that participants in this study tended to have relatively low levels of pain and disability at baseline. They also excluded those with symptomatic radiculopathy or signs of cauda equina syndrome. See the paper for a full list of exclusion and inclusion criteria.

[Full paper saved on Benefits of Vigorous Physical Activity folder}

Running may not be suitable for patients with severe, irritable symptoms, especially if associated with being in more extended, upright positions or impact.

Return to run testing

A test run of up to 2 minutes was used to help determine the starting point of the run-walk programme. I like this approach and it’s something I would use clinically:

“Participants who could jog comfortably for (a) 0-44s started at stage one of the programme; (b) 45-89s started at stage two of the programme and (c) 90-120s started at stage three of the programme.” Neason et al. (2024)

This is similar to our return to run testing in Running Repairs Online where we suggest a short test run to assess response and guide progression.

Run-walk programme

I’d recommend reading the paper in full and in particular looking into the run-walk programme as it’s a nice example of a graded plan that gradually replaces walking with running and gives the patient control of their progression.

Note the start and end points of the programme - stage 1 begins with 15 secs of running and 120 secs of walking repeated 6 to 10 times and done 3 times per week. On average this meant total running distance began at 1.1km in week 1 and increased to 2.7km by week 12. However, within this was significant individual variation.

The key point here is to be realistic with where to start and how much someone will be able to progress in 12 weeks, especially if they have been unable to exercise for some time due to pain.

Limitations

Every study has limitations, in this one the fact that improvements didn’t exceed the minimum clinically meaningful difference is important to note. This may, in part, be due to the baseline symptoms. For example, current pain measured by visual analogue scale (VAS) was 30.80 on average at baseline, it reduced to an average of 14.25 at 12 weeks. This didn’t reach the 20 point reduction that would be considered clinically meaningful despite the fact that pain score has actually halved.

The intervention group also received optional warm up exercises and more regular contact with health professionals that the control group which may have influenced result.

Clinical takeaway

The current evidence suggests running is not harmful for the back and may improve spine health and help symptoms and disability associated with non-specific low back pain. However, it’s unlikely to be suitable for everyone or every pathology so I tend to use 3 criteria for guidance on when to suggest running for non-specific low back pain:

⦁ The patient wants to run and is happy to use it as a treatment strategy

⦁ Symptoms are mild to moderate and they can manage a short test run (e.g. 2 mins) with minimal pain

⦁ There are no contraindications such as cauda equina syndrome or severe, irritable symptoms that are likely to worsen with running

Next week I'll be sharing some advice on the management of Patellofemoral Pain in runners and reflecting on new guidance that's just been published. I'm looking forward to sharing that with you, look out for the subject line, "What's current 'best practice' for PFP?" Best wishes, Tom

--------------------

What Causes Disc Herniations?

Physio Matters and Tom Jesson Jan 01, 2024

Three camps assemble

It all starts in the 1930s, in Massachusetts [1] [2]. A surgeon receives a patient who has developed sciatica after a skiing accident. The surgeon, William Mixter, operates on the skier's spine and removes a piece of whitish gunk. Mixter isn’t surprised, because he has removed plenty of these bits of whitish gunk before, and he knows what they are: benign tumours.

But then the skier's doctor gets involved. The doctor, Joseph Barr, says that Mixter’s benign tumour diagnosis doesn’t sound quite right. A tumour should cause insidious pain, but the skier's pain had started suddenly, after an accident. Fair enough, Mixter says, and together he and Barr investigate.

They look more closely at the whitish gunk from the skier’s spine, and at a lot of other pieces of similar material that Mixter had kept from previous similar operations. And they realise that all these pieces of gunk are, as Barr guessed, not tumours at all. In fact, they're disc material. Disc material that has burst out from its home in the centre of the intervertebral disc.

Mixter and Barr’s discovery sets the template for our early understanding of what causes disc herniations: that they’re the result of a trauma. In 1938, for example, one physician writes that "It is the opinion of most authors that abnormal protrusion of an intervertebral disk into the spinal canal is in the majority of cases the result of trauma" [3]. And another, in 1942, that "trauma is the precipitating factor in most cases" [4]. By trauma, most physicians mean something sudden, but some also mean gradual trauma by repeated insults over time; the "slight shocks of normal life" [5].

Whether sudden or gradual, the earliest understanding of why discs herniate is essentially this: too much force goes through the disc, which makes it break. Let's call this school of thought the ‘Too Much Load Camp’.

As it happens, it only takes a few years for many in the Too Much Load Camp to appreciate that only a minority of people with disc herniations actually report a trauma [6] [7]. As early as 1948, Falconer writes that trauma has been “overemphasised” [5]. Another physician notes that

"70-80% of patients give no history of injury. It is reasonable to assume that injury is never the sole causative agent and, when evident, is only an additional factor" [8].

Where do mid-century physicians go when they leave the Too Much Load Camp?

Well, they had long observed that while some discs stay plump, white and healthy, very early in life some others become thinned, yellow and fissured. On inspection, they can see that these particularly unhealthy discs have slipped into a nasty state of imbalance between catabolic and anabolic activity. They label them as degenerated [8][9].

If it’s not trauma that makes discs herniate, they hypothesise, then it must be this degeneration. “There are other more important basic factors (than trauma)”, writes Naylor in 1962, “(herniations) most probably develop as a result of a more general collagen/polysaccharide disorder”. In other words, it’s not the load placed on the disc, but the qualities of the disc itself that cause it to weaken and fail. Let’s call this new school of thought the ‘Unhealthy Disc Camp’.

So if the Unhealthy Disc Camp says that degeneration causes herniations, then what causes degeneration?

It’s partly, they say, systemic health. If you smoke, drink, have diabetes or vascular diseases, sleep poorly, work more than you rest and so on, then your discs have an even harder time maintaining themselves [10–13]. Smoking, for example, reduces the metabolic activity in your discs and weakens their stricture [14–16].

And it’s partly just that discs are particularly vulnerable to degenerating because they are avascular [11]. In fact, they’re the largest avascular structures in the body. That means that they have to acquire all of their nutrients and expel all of their waste products using diffusion, which is a comically inefficient way for such a large, highly-loaded tissue to maintain itself. No wonder they fail so often.

Let’s fast forward to the nineties. Researchers have long suspected that disc degeneration is hereditary [8], and a group in Finland decides to find out. They recruit lots of sets of twins with different exposures to the usual risk factors for disc herniations [17]. For example, maybe one twin is a farmer and the other is a reporter; or one is a smoker and the other isn't. Then they put all the sets of twins in MRI machines to look at their discs. And the results are emphatic: lifestyle factors have barely influenced those twins' discs at all. The farmer twin has about the same discs as the reporter twin, and the smoking twin has about the same discs as the non-smoking twin.

With the Twin Spine Studies, what we can call ‘All In The Genes Camp’ is formed. “61% of the variance in disc degeneration is explained by familial aggregation”, the authors write a few years later, summarising their findings. “Disc degeneration, which was once viewed as a result of ageing and ‘wear and tear’ from mechanical insults and injuries is now viewed as being determined in great part by genetic influences" [17].

How does your genetic makeup make you more likely to have a disc herniation? People in the All In The Genes camp don’t claim that there's one gene for disc herniations, but that you might be predisposed by a complex interplay of multiple genes [18] [19]. Those multiple genes might, for example, conspire to make your discs’ collagen matrix weaker, or make the enzymes in your discs more active. That means that ultimately, as you get older, your discs are going to do what they’re going to do - whatever your occupation or smoking status.

Against my camp

I don’t know what camp, if any, you were in before you started reading this piece. Not too long ago I was in All In The Genes Camp. But now, I’m not so sure. I still think the genetic explanation is the single most well-evidenced of the three. But I think it’s easy - and common - to over-state genetic influence on disc herniations.

For one thing, the Twin Spine Studies studied disc degeneration, not herniation, and they’re not the same thing. Not only that, but there are also some technical issues that make twin studies, especially older twin studies, liable to overestimate heritability see [20] [21].

But one of the main reasons to take a step back from All In The Genes Camp is right there in the results section of the Twin Spine Studies, it’s just often overlooked: the estimate of familial influence on disc degeneration in the lower lumbar discs, i.e. the ones that herniate the most often, was just 32% [17]. That’s hardly a slam dunk for the All In The Genes! To put it in context, a heritability index of 32% means lower lumbar disc degeneration is about as heritable as anxiety disorder, tobacco and alcohol misuse, neuropathic pain and low back pain [22–24]. And yet we rarely hear anyone say those things are ‘just genetic’. The slightly boring fact is that practically all complex conditions are heritable, but none are pre-determined.

To be clear, the Twin Spine Studies’ estimate of occupation and lifestyle factors is much, much smaller than its estimate of familial influence. So genetics is clearly extremely important. But the studies’ biggest category of influence on lower lumbar disc health wasn’t, in fact, familial influence. It was just labelled… ‘Unexplained’!

In defence of that other camp.

Before I started researching this, there was also one camp I certainly wasn’t in, and that was Too Much Load camp. So déclassé! Now, I’m not so sure of that, either.

True, the evidence suggests that occupational and recreational loading has only a modest (but non-zero!) effect on disc herniations [25–28]. But research into occupational and recreational exposure can’t account for brief, one-off spikes of excess load: a weekend spent moving house, for example, or a slip on the ice… And some researchers argue that it’s just these spikes of excess load - injuries, essentially - that are pivotal in the life course of a disc, and can set it on the long path of structural failure and eventual herniation [29–31]. In fact, such injuries would not have to be particularly dramatic, since genetic predisposition might weaken a disc so much that something fairly innocuous could cause structural damage: sneezing while sitting awkwardly, twisting while making the bed...

And Too Much Load theory does explain something that genetics cannot: why so many people have just one or two herniated discs, while the rest of their spine is fine; and why those herniated discs are frequently the lower lumbar ones, i.e. the ones that work the hardest [32–34]. As Adams and Dolan argue, the most parsimonious explanation for this is discrete trauma [30].

This all flies in the face of the prevailing optimism, in some quarters, that discs adapt well to load and heal from injuries. And it’s true of course that discs adapt; it would be strange if they didn’t [35]. But I think it’s easy to overstate how well they do it. The best evidence that discs get healthier with exercise is all in recreational runners [36–38], but recreational running is the exact type of predictable, moderate load that lab studies tell us their discs should love [39], and therefore adaptation to running is hardly good evidence of discs’ anabolic power more generally. On the contrary, the laboratory evidence - and in fact some of those studies in runners! - still tells us that higher-magnitude load is probably catabolic for discs [38] [39].

In any case, the runners-have-healthier-discs studies don't actually tell us that the discs are healthier because of the running. After all, compared to non-exercisers runners surely have many other healthy habits and genetic advantages that might make for healthier discs. In fact, an RCT found that a running intervention did not make discs healthier (or unhealthier) [40].

And when it comes to healing from injury, well, they definitely can’t do that. “Adult discs are incapable of repairing gross defects”, write Adams and Dolan [30]; “it is clear that an already damaged or degenerate IVD is unlikely to respond to loading in the same way that a healthy IVD does”, say Belavý and colleagues [41].

Tyre-d of fighting

So, I’ve sheepishly taken down the flag I was flying for All In The Genes Camp, and given a begrudging nod of acknowledgement to the dinosaurs in Too Much Load Camp. I’m neutral now.

And I have good company! Joseph Barr, the doctor we met earlier, the one who started all this trouble back in the 1930s, never threw his lot in with any of the three camps. In 1951 he explained his position by likening disc herniations to a car tyre failure:

“The tyre, when it leaves the factory, may have a defect in the fabric (congenital weakness) so that it blows out while rolling along a smooth road. A tyre may blow out when it strikes a stone or curb (acute trauma), or it may give way thousands of miles later. A tyre exposed to gasoline ages rapidly, and degenerative change produces early tyre failure [42]".

I think genetics, or ‘congenital weakness’ as he calls it, turned out to be far more important than Barr expected; but his analogy still holds. It captures well that while the various causes of disc herniations are interrelated, each one might predominate in different cases.

All in all, I think that any strong opinion on what causes disc herniations probably stands on weak foundations. And while it’s unpleasant to hear that your camp isn’t perfect, and even more unpleasant to hear that your enemies’ camp might have some good points, we should be glad that we have more ways to help patients’ make sense of their story - and less reason to restrict them or dictate to them based on our camp’s creed.

Reference List

1. Mixter WJ, Barr JS. Rupture of the Intervertebral Disc with Involvement of the Spinal Canal. N Engl J Med. 1934 Aug 2;211(5):210–5.

2. Parisien RC, Ball PA. William Jason Mixter (1880-1958). Ushering in the “dynasty of the disc.” Spine. 1998 Nov 1;23(21):2363–6.

3. Love JG, Walsh MN. Protruded Intervertebral Disks: Report of One Hundred Cases In Which Operation Was Performed. J Am Med Assoc. 1938 Jul 30;111(5):396–400.

4. Eck DB. Rupture of the intervertebral disc. Am J Surg. 1942 Oct;58(1):3–15.

5. Falconer MA, McGeorge M, Begg AC. Observations on the cause and mechanism of symptom-production in sciatica and low-back pain. J Neurol Neurosurg Psychiatry. 1948 Feb 1;11(1):13–26.

6. Eyre-Brook AL. A study of late results from disk operations; present employment and residual complains. Br J Surg. 1952 Jan;39(156):289–96.

7. Suri P, Hunter DJ, Jouve C, Hartigan C, Limke J, Pena E, et al. Inciting Events Associated with Lumbar Disk Herniation. Spine J Off J North Am Spine Soc. 2010 May;10(5):388–95.

8. Naylor A. The Biophysical and Biochemical Aspects of Intervertebral Disc Herniation and Degeneration. Ann R Coll Surg Engl. 1962 Aug;31(2):91–114.

9. Friberg S, Hirsch C. Anatomical and Clinical Studies on Lumbar Disc Degeneration. Acta Orthop Scand. 1949 Jan;19(2):222–42.

10. Kelsey JL, Githens PB, O’Conner T, Weil U, Calogero JA, Holford TR, et al. Acute prolapsed lumbar intervertebral disc. An epidemiologic study with special reference to driving automobiles and cigarette smoking. Spine. 1984 Sep;9(6):608–13.

11. Pinheiro-Franco JL, Vaccaro AR, Benzel EC, Mayer HM, editors. Advanced Concepts in Lumbar Degenerative Disk Disease [Internet]. Berlin, Heidelberg: Springer Berlin Heidelberg; 2016 [cited 2021 Feb 15].

12. Frymoyer JW. Lumbar disk disease: epidemiology. Instr Course Lect. 1992;41:217–23.

13. Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine. 1995 Jun 1;20(11):1307–14.

14. Akmal M, Kesani A, Anand B, Singh A, Wiseman M, Goodship A. Effect of Nicotine on Spinal Disc Cells: A Cellular Mechanism for Disc Degeneration. Spine. 2004 Mar 1;29(5):568.

15. Holm S, Nachemson A. Nutrition of the Intervertebral Disc: Acute Effects of Cigarette Smoking: An Experimental Animal Study. Ups J Med Sci. 1988 Jan 1;93(1):91–9.

16. Huang W, Qian Y, Zheng K, Yu L, Yu X. Is smoking a risk factor for lumbar disc herniation? Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc. 2016 Jan;25(1):168–76.

17. Battié 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 Jan;9(1):47–59.

18. Chan D, Song Y, Sham P, Cheung KMC. Genetics of disc degeneration. Eur Spine J. 2006 Aug;15(Suppl 3):317–25.

19. Teles Filho RV, Abe G de M, Daher MT. Genetic Influence in Disc Degeneration - Systematic Review of Literature. Rev Bras Ortop. 2020 Apr;55(2):131–8.

20. Turkheimer E. Arsonists at the Cathedral. Wedding D, editor. PsycCRITIQUES [Internet]. 2015 Oct 5 [cited 2023 Dec 16];60(40).

21. Walls CB, Snell A, McLean DJ, Pearce N. An updated critique of the use of the Twin Spine Study (2009) to determine causation of low back disorder. N Z Med J. 2019 May 3;132(1494):57–9.

22. Polderman TJC, Benyamin B, De Leeuw CA, Sullivan PF, Van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015 Jul;47(7):702–9.

23. Momi SK, Fabiane SM, Lachance G, Livshits G, Williams FMK. Neuropathic pain as part of chronic widespread pain: environmental and genetic influences. Pain. 2015 Oct;156(10):2100–6.

24. Nielsen CS, Knudsen GP, Steingrímsdóttir ÓA. Twin studies of pain. Clin Genet. 2012 Oct;82(4):331–40.

25. Seidler A, Bergmann A, Jäger M, Ellegast R, Ditchen D, Elsner G, et al. Cumulative occupational lumbar load and lumbar disc disease – results of a German multi-center case-control study (EPILIFT). BMC Musculoskelet Disord. 2009 May 7;10(1):48.

26. Kuijer PPFM, Verbeek JH, Seidler A, Ellegast R, Hulshof CTJ, Frings-Dresen MHW, et al. Work-relatedness of lumbosacral radiculopathy syndrome: Review and dose-response meta-analysis. Neurology. 2018 Sep 18;91(12):558–64.

27. Zhang Y gang, Sun Z, Zhang Z, Liu J, Guo X. Risk factors for lumbar intervertebral disc herniation in Chinese population: a case-control study. Spine. 2009 Dec 1;34(25):E918-922.

28. Ahsan MK, Matin T, Ali MI, Ali MY, Awwal MA, Sakeb N. Relationship between physical work load and lumbar disc herniation. Mymensingh Med J MMJ. 2013 Jul;22(3):533–40.

29. Lama P, Claireaux H, Flower L, Harding IJ, Dolan T, Le Maitre CL, et al. Physical disruption of intervertebral disc promotes cell clustering and a degenerative phenotype. Cell Death Discov. 2019;5(1).

30. Adams MA, Lama P, Zehra U, Dolan P. Why do some intervertebral discs degenerate, when others (in the same spine) do not?: Why Do Some Intervertebral Discs Degenerate? Clin Anat. 2015 Mar;28(2):195–204.

31. Wade KR, Robertson PA, Thambyah A, Broom ND. “Surprise” Loading in Flexion Increases the Risk of Disc Herniation Due to Annulus-Endplate Junction Failure: A Mechanical and Microstructural Investigation. Spine. 2015 Jun 15;40(12):891–901.

32. Cheung KMC, Karppinen J, Chan D, Ho DWH, 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 Apr;34(9):934–40.

33. Näther P, Kersten JF, Kaden I, Irga K, Nienhaus A. Distribution Patterns of Degeneration of the Lumbar Spine in a Cohort of 200 Patients with an Indication for Lumbar MRI. Int J Environ Res Public Health. 2022 Mar 21;19(6):3721.

34. Sääksjärvi S, Kerttula L, Luoma K, Paajanen H, Waris E. Disc Degeneration of Young Low Back Pain Patients: A Prospective 30-year Follow-up MRI Study. Spine. 2020 Oct 1;45(19):1341–7.

35. Brickley-Parsons D, Glimcher MJ. Is the chemistry of collagen in intervertebral discs an expression of Wolff’s Law? A study of the human lumbar spine. Spine. 1984 Mar;9(2):148–63.

36. Owen PJ, Hangai M, Kaneoka K, Rantalainen T, Belavy DL. Mechanical loading influences the lumbar intervertebral disc. A cross-sectional study in 308 athletes and 71 controls. J Orthop Res [Internet]. 2020 [cited 2020 Jul 22];n/a(n/a).

37. Mitchell UH, Bowden JA, Larson RE, Belavy DL, Owen PJ. Long-term running in middle-aged men and intervertebral disc health, a cross-sectional pilot study. PLOS ONE. 2020 Feb 21;15(2):e0229457.

38. Belavý DL, Quittner MJ, Ridgers N, Ling Y, Connell D, Rantalainen T. Running exercise strengthens the intervertebral disc. Sci Rep. 2017 Apr 19;7(1):45975.

39. Shapiro IM, Risbud MV, editors. The Intervertebral Disc: Molecular and Structural Studies of the Disc in Health and Disease [Internet]. Vienna: Springer Vienna; 2014 [cited 2020 Jul 27].

40. Owen PJ, Miller CT, Rantalainen T, Simson KJ, Connell D, Hahne AJ, et al. Exercise for the intervertebral disc: a 6-month randomised controlled trial in chronic low back pain. Eur Spine J. 2020 Aug;29(8):1887–99.

41. Belavý DL, Albracht K, Bruggemann GP, Vergroesen PPA, van Dieën JH. Can Exercise Positively Influence the Intervertebral Disc? Sports Med Auckl NZ. 2016 Apr;46(4):473–85.

42. Barr JS. Protruded discs and painful backs. J Bone Joint Surg Br. 1951 Feb 1;33-B(1):3–4.