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British Journal of Healthcare and Medical Research - Vol. 10, No. 1
Publication Date: January, 25, 2023
DOI:10.14738/jbemi.101.13800. Horschig, A., Lock, A., Williams, B., & Johnson, D. (2023). Does A Temporary Increase in Glycosaminoglycan (GAG) Indicate Positive
Intervertebral Disc Adaptation? British Journal of Healthcare and Medical Research, 10(1). 27-32.
Services for Science and Education – United Kingdom
Does A Temporary Increase in Glycosaminoglycan (GAG) Indicate
Positive Intervertebral Disc Adaptation?
Aaron Horschig
College of Functional Movement Clinicians,
AUS, USA & NZ
Andrew Lock
College of Functional Movement Clinicians,
AUS, USA & NZ
Brogan Williams
College of Functional Movement Clinicians,
AUS, USA & NZ
David Johnson
College of Functional Movement Clinicians,
AUS, USA & NZ
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, many unanswered questions
remain regarding intervertebral discs (IVDs). Recently, some claim 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 investigated the IVD Glycosaminoglycan (GAG) increases
in elite rowers over the course of a training period, which was to indicate a positive
adaptation to training based on the assumption that GAG is decreased in discs with
degeneration. A cause-and-effect relationship does not exist and in fact, is unlikely
to exist particularly with a historically high prevalence of disc degeneration in
rowers. The Frenken paper supports the notion that the GAG content alters in
response to certain stimuli; however, we cannot conclude that a temporary increase
in GAG content supports the hypothesis that the IVD adapts positively to load. An
alternative postulate is that repetitive biomechanical loading of the intervertebral
disc through intra-lumbar flexion (as observed in rowing) does stimulate nutrient
transport across the vertebral endplates; however, this biochemical response is of
limited benefit and should not be perceived as a positive adaptation to the overall
longevity and health of the disc. In this context, the elevation in GAG may be more
appropriately interpreted as a maladaptive indicator of undesirable biomechanical
intra-lumbar flexion stress that progressively drives cartilaginous endplate
sclerosis leading ultimately to the clinically observed accelerated disc
degeneration, future back pain symptoms, and reduced GAG concentration in
rowers. This contrasting interpretation is consistent with the clinical observation
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of intra-lumbar flexion biomechanical stress, the transient rise in GAG followed by
a reduction that correlates with the radiological findings and back pain symptoms
evolving over time in elite rowers.
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, many unanswered questions remain
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].
However, is this study really showing the disc positively adapts?
To understand the Frenken paper, you first need to understand intervertebral disc anatomy
and physiology.
The intervertebral disc has three components.
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
NUCLEUS PULPOSUS (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].
ANNULUS FIBROSUS (AF)
The annulus fibrosus is mostly avascular and nerves innervate only the outer third of the disc.
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
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Horschig, A., Lock, A., Williams, B., & Johnson, D. (2023). Does A Temporary Increase in Glycosaminoglycan (GAG) Indicate Positive Intervertebral Disc
Adaptation? British Journal of Healthcare and Medical Research, 10(1). 27-32.
URL: http://dx.doi.org/10.14738/jbemi.101.13800
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 millimetres 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].
CARTILAGINOUS END PLATE (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.
FRENKEN PAPER
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.
GAG CONTENT + IVD ADAPTATION
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]. This interpretation may be misguided. 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 degenerative changes of endplate sclerosis (more so in the NP than the AF) [22].
GAG confers the physiological characteristics essential for the IVD to perform its function as
one of many elements that create biomechanical stability to the semi rigid support strut that is
the Lumbar spine. It comes as no surprise that under biomechanical stress and loading of intra- lumbar flexion (ILF), the GAG concentration would not transiently rise. This is indifferent to the
analogous development of uncovertebral osteophytes and facet hypertrophy when the spinal
motion segment is undesirably biomechanically in the absence of stability. In this context with
ILF of elite rowing training. 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].
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.”
This is more appropriately termed accelerated degeneration or degeneritis. Degeneritis is
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pathological and associated with pain and disability, whereas degeneration is a normal pain- free process of aging. An alternative postulate is that repetitive biomechanical loading of the
intervertebral disc through ILF as observed in rowing does stimulate nutrient transport across
the vertebral endplates and an increase in GAG has been observed however this biochemical
response is of limited benefit and should not be perceived as adaptive to the overall longevity
and health of the disc.
In this context, the elevation in GAG may be more appropriately interpreted as a maladaptive
indicator of undesirable biomechanical ILF stress that progressively drives cartilaginous
endplate sclerosis leading ultimately to the clinically observed accelerated disc degeneration
(degeneritis), future back pain symptoms, and reduced GAG concentration in rowers. This
contrasting interpretation is consistent with the clinical observation of ILF biomechanical
stress, the transient rise in GAG followed by a reduction that correlates with the radiological
findings and back pain symptoms evolving over time in elite rowers.
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 a positive adaptation. GAG is associated with degeneration, but not a direct causal
relationship. The observed rise in GAG is more appropriately a response and an indicator of
biomechanical stress across the lumbar motion segment. In contrast to perceiving this as a
beneficial adaptive response, it should be viewed as a sign of the very early stages of endplate
sclerosis with a predictable likelihood of symptomatic degeneritis and reduced GAG
concentration. With this understanding, we cannot conclude whatsoever that a temporary
increase in GAG content supports the hypothesis that the IVD adapts positively to load. We can
posit that future research should focus on enhancing movement proficiency underload or with
training to shield biomechanical stress and maintain high levels of functional capacity and
performance simultaneously with IVD health.
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Horschig, A., Lock, A., Williams, B., & Johnson, D. (2023). Does A Temporary Increase in Glycosaminoglycan (GAG) Indicate Positive Intervertebral Disc
Adaptation? British Journal of Healthcare and Medical Research, 10(1). 27-32.
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