Does the Intervertebral Disc Adapt to Load?

ISSN: 2321 9653; IC Value: 45.98; SJ Impact Factor: 7.538 Volume 10 Issue XI Nov 2022 Available at www.ijraset.com

Does the Intervertebral Disc Adapt to Load?

Dr. Aaron Horschig1 , Dr. Andrew Lock2 , Dr. Brogan Williams3 1DPT, CSCS, 2D.D., MPhysio, 3Ph.D., MSc United States of America, New Zealand & Australia

Abstract: Many in the scientific community have been debating the extent to which the spine can adapt. While it is widely accepted that vertebral bones can adapt and become stronger/denser with appropriately dosed loading, there are still many unanswered questions regarding intervertebral discs (IVDs). Recently, some are claiming that IVDs can adapt to stress under load and become stronger and more resilient over time based on the findings from a recent study “Imaging of exercise induced spinal remodeling in elite rowers” by Frenken et al 2022 in the Journal of Science and Medicine in Sport. The Frenken paper investigates the Glycosaminoglycan (GAG) content of the IVD amongst elite rowers over the course of a training period. They found a temporary increase in this protein and believed that it indicates lumbar disc “remodeling effects” in response to training. This study does show that repetitive loading of the spine does support nutrient transport across the vertebral endplates and an increase in GAG. However, with research showing that a reduction in GAG content is associated with IVD degeneration (a negative adaptation), many have been led to believe the opposite to be accurate; an increase in GAG content means the disc is positively adapting. However, this assumption may be incorrect as it is based on an association, not causation. The proof of nutrient availability isn’t the same as mechanism utility. If in fact, the disc was truly adapting we would likely NOT see an overwhelming amount of research showing an extremely high prevalence of disc degeneration in rowers. The Frenken paper and many more do support the notion that the GAG content alters in response to certain stimuli; however, we can NOT conclude that a temporary increase in GAG content supports the hypothesis that the IVD adapts positively to load.

I. INTRODUCTION

Many in the scientific community have been debating the extent to which the spine can adapt over the last few years. While it is widely accepted that vertebral bones can adapt and become stronger/denser with appropriately dosed loading, there are still many unanswered questions regarding intervertebral discs (IVDs). Recently some are claiming that IVDs can adapt to stress under load and become stronger and more resilient over time based on the findings from a recent study “Imaging of exercise induced spinal remodeling in elite rowers” by Frenken et al 2022 in the Journal of Science and Medicine in Sport [1].

A. However, is this study really showing the disc adapts? To understand the Frenken paper, you first need to understand intervertebral disc anatomy and physiology. The intervertebral disc has three components.

B. Intervertebral discs (IVDs) consist of

1) The outer collagenous structure the annulus fibrosus (AF)

2) The inner nucleus pulposus (NP)

3) The cartilage end plates (CEP) on the superior and inferior aspect

II. NUCLEUSPULPOSUS(NP)

The NP has no blood or nerve supply. A normal NP is a gel like structure that has a very high viscosity. It is composed of small proteins called proteoglycans and an intermolecular water gel held loosely by an irregular network of fine Type 2 collagen and elastin fibers. The major proteoglycan of the disc is aggrecan. Aggrecan, because of its high anionic glycosaminoglycan content (i.e., chondroitin sulfate and keratin sulfate), provides the osmotic properties needed to resist compression forces [2,3]. The NP acts hydrostatically by transmitting pressure evenly to the annulus fibrosus and end plates in every direction according to Pascal’s principle [23]. On MRI, the hyper intense signal of the nucleus on T2 weighted images have been shown to correlate directly with the proteoglycan concentration in the NP [5]. Chemical Exchange Saturation Transfer (CEST) imaging, as used in the Frenken study, is a non invasive imaging technique that allows the determination of GAG content in IVDs [1].

ISSN: 2321 9653; IC Value: 45.98; SJ Impact Factor: 7.538 Volume 10 Issue XI Nov 2022 Available at www.ijraset.com

III.ANNULUSFIBROSUS(AF)

The annulus fibrosus is mostly avascular (very little blood supply) and only the outer third of the disc is innervated by nerves. It consists primarily of Type 1 Collagen fibers (remember the NP is Type 2). The rings of the annulus are called the lamellae. It is very different in structure, composition, and function from the NP. The very outer AF has a very limited blood supply, such that the annulus as an entire structure is considered to be avascular. Due to its avascular nature, it’s likely a tear in the AF does not adapt or remodel in the same way other tissue or bone would [8]. Instead, structural changes are potentially irreversible as adult discs have limited healing potential [10]. Research suggests that the collagen turnover time in articular cartilage is approximately 100 years, and it may be even longer in the annulus fibrosus [9,10]. Furthermore, injuries that affect the inner annulus or endplate can decompress the nucleus, slowing the “healing” processes which can then result in severe degenerative changes [7]. Injury to the outer annulus has been shown to result in granulation tissue, with research showing only the outer few millimeters are bridged by scar tissue, likely causing the disc to never fully heal and never return to pre injury status thus leading to the differentiation of “healing” vs “positive adapting” [6,7]. While there is GAG content in the AF, there are significantly lower GAG values in this part of the disc compared with the NP [4].

IV.CARTILAGINOUSENDPLATES(CEP)

Cartilaginous End Plates (CEP) are a layer of cartilage that is positioned in between the disc and the vertebral bone (think of it as the leather stretched over the top of a drum). It plays a crucial role in the maintenance of the mechanical environment as well as the proper nutrition of the avascular discs.

V. FRENKENPAPER

The Frenken paper investigates the Glycosaminoglycan (GAG) content of the IVD amongst elite rowers over the course of a training period. They found a temporary increase in this protein (via higher gagCEST values) and believed that it indicates lumbar disc “remodeling effects” in response to training. An interesting aspect of their findings was that the NP had almost a 2 FOLD increase in GAG compared to the AF. This increase however returned to normal levels after the rowing programming ceased. So, while there was an increase in GAG noted in both areas of the IVD, there was a significantly more increase in the NP.

VI.GAGCONTENT+IVDADAPTATION

The results of this study show that repetitive loading of the spine does support nutrient transport across the vertebral endplates. However, with research showing that a reduction in GAG content is associated with IVD degeneration (a negative adaptation), many have been led to believe the opposite to be true; an increase in GAG content means the disc is positively adapting [14]. However, this assumption may be incorrect as it is based on an association, not causation. The proof of nutrient availability isn’t the same as mechanism utility (simply put, it doesn’t mean the uptake of such nutrients is occurring). What we can conclude is that GAG is a protein within the extracellular matrix of the IVD that has been found to temporarily increase in response to loaded exercise and decrease in response to injury (more so in the NP than the AF) [22]. While gagCEST of lumbar IVDs may be helpful to investigate early disc degeneration when specifically looking at the NP, it is likely not a helpful way to determine physical changes in the AF. It confirms the biological, and physiological, nature of cyclic compression for nuclear health. If in fact, the disc was truly adapting we would likely NOT see an overwhelming amount of research showing an extremely high prevalence of disc degeneration in rowers [19 21]. In fact, it is important to consider that the authors themselves said, “intensive athletic exercise at a professional level is associated with early degenerative changes, including disc herniation.”

VII. CONCLUSION

We can establish that yes, the Frenken paper and many more do support the hypothesis that the NP and the AF increase in GAG in response to certain stimuli [15 18]. However, this does NOT prove positive adaptation. GAG is associated with degeneration, but not a direct causal relationship. Additionally, proving that nutrients are available vs the mechanism involved in the uptake, partitioning, and usage of those nutrients are two very different things. Various animal studies show the AF does not heal effectively, and even when it may, it’s with very poor quality and likely never back to full function or pre injury status. In fact, some studies show the inner portion of the annulus can remain damaged long term [6 10]. With this understanding, we can NOT conclude whatsoever that a temporary increase in GAG content supports the hypothesis that the IVD adapts positively to load.

ISSN: 2321 9653; IC Value: 45.98; SJ Impact Factor: 7.538 Volume 10 Issue XI Nov 2022 Available at www.ijraset.com

REFERENCES

[1] Frenken M, Schleich C, Radke KL, Müller Lutz A, Benedikter C, Franz A, Antoch G, Bittersohl B, Abrar DB, Nebelung S. Imaging of exercise induced spinal remodeling in elite rowers. J Sci Med Sport. 2022 Jan;25(1):75 80.

[2] Miles, D.E., Mitchell, E.A., Kapur, N., Beales, P.A. and Wilcox, RK. (2016) Peptide: Glycosaminoglycan Hybrid Hydrogels as an Injectable Intervention for Spinal Disc Degeneration. Journal of Materials Chemistry B, 4, 3225 3231.

[3] An, H.S., Anderson, P.A., Haughton, V.M., Iatridis, J.C., Kang, J.D., Lotz, J.C., et al. (2004) Introduction: Disc Degeneration: Summary. Spine, 29, 2677 2678.

[4] Haneder, S., Apprich, S.R., Schmitt, B., Michaely, H.J., Schoenberg, S.O., Friedrich, K.M., et al. (2013) Assessment of Glycosaminoglycan Content in Intervertebral S.

[5] Mallio, C. A., Vadalà, G., Russo, F., Bernetti, C., Ambrosio, L., Zobel, B. B., Quattrocchi, C. C., Papalia, R., & Denaro, V. (2022). Novel Magnetic Resonance Imaging Tools for the Diagnosis of Degenerative Disc Disease: A Narrative Review. Diagnostics, 12(2), 420. https://doi.org/10.3390/diagnostics12020420

[6] Latz D, Frenken M, Schiffner E, Knautz M, Quante WA, Windolf J, Grassmann JP, Jungbluth P, Schleich C. Assessment of glycosaminoglycan content in intervertebral discs of patients with leg length discrepancy: A pilot study. J Orthop. 2019 Apr 8;16(5):363 367. DOI: 10.1016/j.jor.2019.03.014. PMID: 31011249; PMCID: PMC6463742.

[7] Melrose J, Ghosh P, Taylor TK, et al. A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus. J Orthop Res 1992;10:665 76.

[8] Kaigle AM, Holm SH, Hansson TH. 1997 Volvo Award winner in biomechanical studies. Kinematic behavior of the porcine lumbar spine: A chronic lesion model. Spine 1997;22:2796 806.

[9] Roughley PJ. Biology of intervertebral disc aging and degeneration: Involvement of the extracellular matrix. Spine 2004;29:2691 9

[10] Verzijl N, DeGroot J, Thorpe SR, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 2000;275: 39027 31.

[11] Adams MA, Freeman BJ, Morrison HP, et al. Mechanical initiation of intervertebral disc degeneration. Spine 2000;25:1625 36

[12] Dickerman RD, Pertusi R, Smith GH. The upper range of lumbar spine bone mineral density? An examination of the current world record holder in the squat lift. Int J Sports Med. 2000 Oct;21(7):469 70.

[13] Walters PH, Jezequel JJ, Grove MB. Case study: Bone mineral density of two elite senior female powerlifters. J Strength Cond Res. 2012 Mar;26(3):867 72.

[14] Silagi, E. S., Shapiro, I. M., & Risbud, M. V. (2018). Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration. Matrix Biology: Journal of the International Society for Matrix Biology, 71 72, 368 379. https://doi.org/10.1016/j.matbio.2018.02.025

[15] DENG Min1, YUAN Jing2, CHEN Wei Tian1, Queenie CHAN3, James F GRIFFITH1, and WANG Yi Xiang1,#. Evaluation of Glycosaminoglycan in the Lumbar Disc Using Chemical Exchange Saturation Transfer MR at 3.0 Tesla: Reproducibility and Correlation with Disc Degeneration* https://sci hub.se/10.3967/bes2016.005

[16] Schleich, C., Müller Lutz, A., Eichner, M., Schmitt, B., Matuschke, F., Bittersohl, B., Zilkens, C., Wittsack, H. J., Antoch, G., & Miese, F. (2016). Glycosaminoglycan Chemical Exchange Saturation Transfer of Lumbar Intervertebral Discs in Healthy Volunteers. SPINE, 41(2), 146 152. https://doi.org/10.1097/brs.0000000000001144
https://sci hub.se/10.1097/BRS.0000000000001144

[17] Schleich, C., Müller Lutz, A., Matuschke, F., Sewerin, P., Sengewein, R., Schmitt, B., Ostendorf, B., Wittsack, H. J., Stanke, K., Antoch, G., & Miese, F. (2015). Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis. Journal of Magnetic Resonance Imaging, 42(4), 1057 1063. https://doi.org/10.1002/jmri.24877
https://sci hub.se/10.1002/jmri.24877

[18] Belavý, D. L., Quittner, M. J., Ridgers, N., Ling, Y., Connell, D., & Rantalainen, T. (2017). Running exercises strengthens the intervertebral disc. Scientific Reports, 7(1). https://doi.org/10.1038/srep45975

[19] Sekine, C., Hirayama, K., Yanagisawa, O., Okubo, Y., Hangai, M., Imai, A., & Kaneoka, K. (2014). Lumbar intervertebral disc degeneration in collegiate rowers. The Journal of Physical Fitness and Sports Medicine, 3(5), 525 530. https://doi.org/10.7600/jpfsm.3.525

[20] Smoljanovic, T., Bojanic, I., Hannafin, J. A., Hren, D., Delimar, D., & Pecina, M. (2009). Traumatic and overuse injuries among international elite junior rowers. The American Journal of Sports Medicine, 37(6), 1193 1199. https://doi.org/10.1177/0363546508331205

[21] Hosea, T. M., & Hannafin, J. A. (2012). Rowing Injuries. Sports Health: A Multidisciplinary Approach, 4(3), 236 245. https://doi.org/10.1177/1941738112442484

[22] Heüveldop et al. DOI: 10.4236/ijcm.2019.104020 269 International Journal of Clinical Medicine Discs Using Chemical Exchange Saturation Transfer at 3.0 Tesla: Preliminary Results in Patients with Low Back Pain. European Radiology, 23, 861 868.

[23] Kushchayev, S. V., Glushko, T., Jarraya, M., Schuleri, K. H., Preul, M. C., Brooks, M. L., & Teytelboym, O. M. (2018). ABCs of the degenerative spine. Insights into Imaging, 9(2), 253 274. https://doi.org/10.1007/s13244 017 0584 z