Research Review by Dr. Shawn Thistle©


Sept. 2006

Study Title:

What is intervertebral disc degeneration, and what causes it?


Adams MA & Roughley PJ

Publication Information:

Spine 2006; 31(18): 2151-2161.


Intervertebral disc pathology has been investigated extensively over the years by scientists and clinicians spanning a wide variety of disciplines and specialties. From anatomy and histology to orthopedic surgery and rehabilitation, disc pathology is a diverse and common problem that must be understood and approached from many angles.

This paper is a review and interpretation of the existing literature on disc anatomy and pathology, culminating in a proposed definition of "disc degeneration" which would help to distinguish disease, physiologic growth and healing processes, aging, and adaptive remodeling. According to these authors, a precise definition of disc degeneration is long overdue, and is currently nonexistent.

Disc Anatomy Review
  • intervertebral discs are pads of fibrocartilage
  • lamellae consist primarily of type I collagen fibres at an angle of approximately 30° - layers occur in alternating directions to increase tensile strength
  • the nucleus pulposus consists of proteoglycan and water gel held loosely by an irregular network of type II collagen and elastin fibres
  • the main proteoglycan in the nucleus is aggrecan, which is very high in anionic glycosaminoglycans (such as chondroitin sulphate and keratin sulphate) provides osmotic properties required to resist compression
Discogenic Pain
  • nociceptive nerve fibres generally penetrate only the outer 1-3 mm of the annulus (in severely injured or painful discs, nerves have been documented closer to the inner annulus)
  • painful discs are always structurally disrupted, and show irregular stress concentrations
  • features of the disc that have been shown to correlate with pain include: disc prolapse, radial fissures, and disc narrowing
  • disc bulging and Schmorl's nodes show are more variably related to pain
Disc Metabolism
  • in adults, blood vessels are restricted to only the outer layers of the annulus metabolite transport is by diffusion (small molecules) and bulk flow (larger molecules)
  • generally, the nucleus has high lactic acid concentration due to anaerobic metabolism resulting from low oxygen tension
  • in vitro experiments have shown chronic oxygen deprivation can lead to disc cells becoming quiescent, while chronic glucose deficiency can kill them
  • all of these factors contribute the discs having limited ability to heal from mechanical or metabolic injury
  • "End plate permeability and, therefore, disc metabolite transport normally decrease during growth and aging, and yet increase in the presence of disc degeneration and following endplate damage. This is one essential difference between aging and degeneration." [pg. 2152]
Disc Healing
  • gross injuries to a disc never heal - for example, annular tears are never remodeled like a bone fracture
  • collagen turnover time in articular cartilage is 100 years, and may be longer in a disc
  • injured discs show increased levels of catabolic cytokines and scar formation, renewed matrix turnover, and more variable collagen fibre diametersv
Disc Aging
  • young discs have a higher water content in the nucleus and inner annulus - only the outermost annulus acts as a tensile restraintv
  • major structural changes to the disc occur during fetal and juvenile growth - this is when the nucleus changes consistency from a translucent fluid to an amorphous tissue
  • this change in the nucleus includes proteoglycan fragmentation, an increase in type I collagen relative to type II collagen (type I fibres also become coarser), and reduced matrix turnover which allows increased cross-linking (leading to characteristic yellow appearance of aging discs)
  • with increasing age - disc water content decreases, particularly in the nucleus, while the entire annulus becomes more fibrous in order to resist compression
  • proteoglycan content declines with age - presumably due to proteolysis
Functional Changes
  • with age, the nucleus becomes decompressed and hydrostatic - this transfers more compressive load to the annulus
Disc Structural Injuries
  • there are 3 types of tears:
    1. circumferential (or delamination) - occur around the outer disc layers and are thought to become prevalent after age 10, particularly in the lumbar spine
    2. peripheral rim - more common in the anterior annulus, and may be associated with bony outgrowths
    3. radial fissures - begin in the nucleus and progress outward, usually posteriorly or postero-laterally
  • radial fissures can be recreated experimentally by repeated flexion and compression
  • "Radial fissures are associated with nucleus "degeneration", but it is not clear which comes first" [pg. 2154]
Disc Prolapse (Herniation)
  • when radial fissures become severe enough to allow migration of nuclear material to the disc periphery - the disc is said to be herniated
  • "severely degenerated" discs do not prolapse in experimental setups, presumably because the nucleus is unable to exert hydrostatic pressure to the annulus
  • in most compressive incidents - the vertebral endplate will represent the "weak link" - accumulating trabecular microdamage which can lead to "vertical" disc bulges into the vertebral bodies with old age
  • these vertical disc movements decompress the nucleus, again transferring compressive force to the annulus
  • subsequent calcification of this nuclear bulge into the endplate is called a Schmorl's node
Disc Narrowing, Bulging, and Osteophytes
  • these three entities are closely related - often summarized with the term "spondylosis"
  • nucleus dehydration (with age or injury as already discussed) decreased nucleus pressure increased vertical loading on the annulus outer annulus bulges outward (or sometimes inward) basically, the disc behaves as a "flat tire"
  • this can transfer up to 50% of compressive load to the posterior neural arch - likely explaining the correlation between disc narrowing and facet arthrosis
Risk Factors for Disc Pathology
  • greatest risk factor is genetic inheritance
  • others include repetitive and high mechanical loading, and smoking
  • disc prolapse is associated with heavy lifting, but not with other features of spinal degeneration

Conclusions & Practical Application:

Multiple factors contribute to disc pathology including genetic inheritance, mechanical loading, smoking, impaired metabolite transport, altered enzyme activity, changes in water content, structural failure, and neurovascular ingrowth. Some are causes, some are effects, and there are others not discussed here.

In the discussion, the authors discuss each major factor in terms of its utility in defining disc degeneration. They suggest that in order to be useful, the definition should distinguish disc "degeneration" from the normal and inevitable physiological processes of growth, aging, and adaptive remodeling. Further, the definition should be clinically relevant to dysfunction or pain.

Using these criteria, the authors suggest the following (all quotes from pg. 2158):

"The process of disc degeneration is an aberrant, cell-mediated response to progressive structural failure"

The cause of this disc degeneration can be explained as follows:

"Plainly, excessive mechanical loading causes a disc to degenerate by disrupting its structure and precipitating a cascade of nonreversible cell-mediated responses leading to further disruption"

"Although we suggest that mechanical loading precipitates degeneration, the most important cause of degeneration could be the various processes that weaken the disc before disruption, or that impair its healing response."

Further, they suggest that the term "degenerative disc disease: should only be applied to a degenerated disc which is also painful.

I found this paper interesting because the authors derived a logical definition for the cause and process of disc degeneration from a huge body of literature. Patients are often labeled with "degenerative disc disease" when it has been repeatedly demonstrated that structural deficits cannot always explain clinical presentation.

The definitions suggested in this paper provide a starting point for further discussion at the very least, and a clear explanation of a multifactorial problem at best