Cervical Degenerative Disk Disease

Epidemiology

Cervical DDD is an age-related phenomenon, as it is in the lumbar spine. Disk degeneration is a natural aging phenomenon, and its prevalence increases with age whether symptoms are present or not. In an MRI study, Boden and associates showed that the disk was degenerated or narrowed at one level or more in 25% of subjects who were less than 40 years old and in almost 60% of subjects who were more than 40 years old. Lehto and colleagues, in another MRI study, showed that abnormalities were found in 62% of subjects who were more than 40 years old, whereas no abnormalities were found in subjects who were less than 30 years old. Among asymptomatic Japanese study subjects, 20% of participants in their 20s and almost 90% of participants who were more than 60 years old had cervical disk degeneration. The most commonly involved disk level in patients who were more than 30 years old was C5-C6. A study by Lawrence and co-workers similarly showed that the C5-C6 and C6-C7 disks were most often degenerated, and the prevalence of cervical disk degeneration increased with age. No differences were found among male and female study subjects. Matsumoto and associates reported that cervical disks were degenerated in 17% and 12% of asymptomatic men and women in their twenties, respectively. In subjects more than 60 years old, the prevalence rose to 86% in men and 89% in women. Moderate to severe cervical degeneration was associated with a past episode or repeated episodes of pain in the neck-shoulder-brachial region. Moderate to severe cervical disk degeneration was associated significantly with lumbar degeneration in both sexes. Although disk degeneration is common in the cervical spine, it appears to begin later in the cervical spine than in the lumbar region.

Pathophysiology

The intervertebral disk is the largest avascular tissue in the human body. Disk nutrition derives from diffusion across the cartilaginous end plates. The intervertebral disk consists of the central nucleus pulposus and the peripherally encircling annulus fibrosus. These structures are important shock absorbers of the spine to body motion. The nucleus pulposus is a remnant of the notochord and consists of the loose network of collagen fibers in a gelatinous fluid that is composed of 85% to 90% water in a young individual. The rest of the matrix is composed of 25% to 35% collagen and 60% to 65% proteoglycans. Aging causes the water content of the nucleus pulposus to decrease, thus resulting in a relative increase of proteoglycan and collagen. The annulus fibrosus is predominantly composed of water (60% to 70%) and, to a lesser degree, collagen (20% to 30%). Unlike in the nucleus pulposus, however, the water content of the annulus fibrosus does not change with age.

Biochemical changes of the spinal unit begin in the nucleus pulposus. With aging, the nucleus pulposus begins to desiccate and loses its mechanical competence. Effective load transmission is no longer possible when this occurs because the normal nucleus pulposus is similar to a contained fluid. Axial loads to the spine are converted to tensile strain on annular fibers and are then transmitted to the vertebral end plates. With continuous loading, creep occurs in the nucleus pulposus. Eventually, the gel structure degenerates. The collagen content of the disk increases while glycoprotein content decreases after the second decade of life. The loss of glycoproteins decreases imbibition pressure. In its relaxed state, the degenerated disk imbibes fluid.

Loading, genetics, and local autocrine factors all influence the rate and degree of disk degeneration. The significant effect of axial loading is evidenced by the high rates of disk degeneration in the lordotic area of the spine. When static compressive stress exceeds the pressure in the disk, water is forced out, thus causing altered intradiskal stress distribution and resulting in a number of harmful, dose-dependent responses. These include apoptosis of the nuclear cells, loss of cellularity, down-regulation of the collagen II and aggrecan gene expression, and increasingly disorganized annulus fibrosis. Cells of the intervertebral disk are metabolically active and are capable of responding to biochemical stimuli. These autocrine factors function as local cellular signals that affect disk degeneration.

The percentage of matrix metalloproteinase-3 (MMP-3)–positive cells correlates with the degree of degeneration on MRI and osteophyte size. Degenerated disks exhibit MMP-3 but no metalloproteinase tissue inhibitor. Disk degeneration is suggested to be caused by an imbalance of MMP-3 and tissue inhibitor of metalloproteinase-1. Cathepsins and other proteolytic enzymes can separate disks from vertebral bodies, thereby affecting the rate of disk degeneration.

The mature annulus fibrosus contains degenerated cells and necrotic debris. Collagen types I and II predominate in the disk. Type I collagen is suited to withstand tensile-type loading and is located in the annulus fibrosus. Type II collagen can sustain tensile loads and is found in the nucleus pulposus. The proteoglycan content of the disk decreases with age. The normal disk contains enzymes active against type II collagen, whereas in the prolapsed disk, the enzyme systems are active against type I collagen. The prolapsed disk contains elastin-degrading enzymes, which are not found in the normal disk. Elastic fibers are located in the annulus fibrosus at the interface of the disk and the vertebral body. The increased presence of elastin- and type I collagen–degrading enzymes in the annulus fibrosus is likely one mechanism for disk herniation. The histologic changes in disk degeneration are seen in adjacent cartilaginous end plates, where neovascularization, capillary wall thickening, and calcification are found.

The normal functions of the annulus fibrosus are to contain the nucleus pulposus and to convert compressive stress to tangential stress. When the nucleus pulposus fails to maintain hydration, strain changes occur at the nucleus-annulus interface. The mechanical effectiveness of the disk decreases with decreasing states of hydration. The disk is no longer able to generate increased intradiskal pressures and is therefore unable to distribute force effectively. The central annular lamellae buckle under constant compressive loading. The disk collapses and causes external concentric bands of annulus fibrosus to bulge outward.

Increased annular stress leads to fibrillation and tearing of annular fibers. In younger patients, disk material prolapses through tears in the annulus fibrosus and causes nerve root or spinal cord impingement. The soft disk herniation causes nerve dysfunction both directly and through vascular compromise of radicular feeder arteries. The exiting nerve root is most commonly affected by disk protrusion. Acute disk herniation and annular degeneration and protrusion are part of a continuum of degeneration that leads to advanced spondylosis. Disk collapse translates into excess motion in the zygapophyseal (facet) joints posteriorly and increased strain in the supporting ligaments. With loss of disk height, the facets begin to override, and uncovertebral joints come into contact, thus forming osteophytes. Decreasing facet competence and increased segmental motion hasten the rate of disk degeneration. Ten years after the disk begins to degenerate, the mechanical competence of the motion segment becomes evident, with facet and uncovertebral joint degeneration. True disk protrusion or a hard disk (osteophytes) can also compress the nerve root and lead to radiculopathy. With continued degeneration, osteophytes along with other pathologic processes, such as disk protrusion or ossification of the posterior longitudinal ligament (OPLL), may compress the central spinal canal. Spinal cord function is affected by vascular insufficiency, and direct mechanical pressure on the neural elements results from central spinal canal stenosis, which may lead to cervical myelopathy.

Risk Factors

DDD has several possible mechanisms, such as decreased proteoglycan and water content, inflammation induced by cytokines such as interleukin-1 and tumor necrosis factor-α, genetics, smoking, occupational load, atherosclerosis, and history of surgery. However, a longitudinal study could not support all suggested DDD theories such as smoking. In addition, the role of body mass index, gender, sports, and alcohol consumption is not certain in the development of DDD of the cervical spine. Smoking was not found to be related to cervical DDD on lateral plain radiographs in a cross-sectional case-control study. No increased risk for herniation was found for sedentary jobs or jobs requiring twisting of the neck, and no increased risk was noted for any sport including weightlifting. In fact, sport activity has been suggested to be protective of the cervical spine. Hence, causal factors for DDD have not been fully established.

Genetics

Hereditary factors could affect disk degeneration through several mechanisms, such as an influence on the size and shape of spinal structures that affect the mechanical properties of the spine and its vulnerability to external forces. Biologic processes associated with the synthesis and breakdown of structural and biochemical constituents of the disk could be partly genetically predetermined, thus leading to vulnerability to accelerated degenerative changes in some persons. The identification of specific genetic influences may eventually provide key insights into underlying mechanisms. Furthermore, for specific genes and some environmental factors, gene-gene interactions and gene-environment interactions may exist.

Another factor that must be considered is age. A particular gene may possibly be associated with DDD only at a certain age. Some genes have been associated with disk degeneration in human beings, including genes coding for collagen type I ( COL1A1 ), collagen type IX ( COL9A2 and COL9A3 ), collagen type XI ( COL11A2 ), interleukin-1, aggrecan, vitamin D receptor (VDR), MMP-3, and cartilage intermediate-layer protein (CILP). At present, only an association of the COL1A1, COL9A2, MMP-3, and VDR genes with DDD has been verified in different ethnic populations. The annulus fibrosus consists mainly of collagen type I, and the nucleus pulposus contains approximately 50% proteoglycans, mainly aggrecan, and 20% collagen type II. Both contain small amounts of collagen types IX and XI. Studies based on a mouse model indicated that mutations in collagen type IX and aggrecan can cause age-related disk degeneration and herniation. Collagen types IX and XI are attractive candidates for lumbar disk degeneration because they serve as minor components in both the annulus fibrosus and the nucleus pulposus ; however, their roles in the cervical spine warrant further investigation. Nonetheless, various genetic studies have noted concomitant cervical and lumbar degenerative changes, findings suggesting that these two regions share common risk factors.