What is Intervertebral Disc Degeneration, and What Causes It?

Michael A. Adams, PhD; Peter J. Roughley, PhD


Spine. 2006;31(18):2151-2161. 

In This Article

Disc Aging

Proteoglycan fragmentation starts during childhood,[36] and with increasing age, the overall proteoglycan and water content of the disc decreases, especially in the nucleus.[21] There is a corresponding increase in collagen content, a tendency for fine type II collagen fibrils in the inner anulus to be replaced by type I fibers as the anulus encroaches on the nucleus, and for type I fibers throughout the disc to become coarser. Loss of proteoglycan fragments from the disc is a slow process owing to the entrapment of the nucleus by the fibrous anulus and the cartilage endplates of the vertebrae.[37] As long as the proteoglycan fragments remain entrapped in the disc, they can fulfill a functional role similar to that of the intact proteoglycan. Reduced matrix turnover in older discs enables collagen molecules and fibrils to become increasingly cross-linked with each other, and existing cross-links become more stable.[28] In addition, reactions between collagen and glucose lead to nonenzymatic glycation (extra cross-links that give old discs their characteristic yellow-brown appearance).[38] Increased cross-linking inhibits matrix turnover and repair in old discs, encouraging the retention of damaged macromolecules[32] and probably leading to reduced tissue strength.

During early childhood, the blood supply to the vertebral endplate decreases, and microstructural clefts and tears become common by the age of 15 years, especially in the nucleus and endplate.[39] Cell density decreases throughout growth,[7] and from skeletal maturity onward, there is a steadily increasing incidence of structural defects extending into the anulus.[26] The nucleus pulposus tends to condense into several fibrous lumps, separated from each other and from the cartilage endplate by softer material.[40] Sequential histologic changes across 9 decades have recently been classified.[39] Generally, these changes affect the endplate first, then the nucleus, and, finally, the anulus, and different spinal levels are affected to a similar extent.

Matrix synthesis decreases steadily throughout life but sometimes increases again in old and severely disrupted discs.[21] Reduced synthesis is partly attributable to decreased cell density, although proteoglycan synthesis rates per cell also decrease.[41] Cell proliferation can occur locally in association with fissures and increased MMP activity.[26,27] Age-related changes in the types of collagens and MMPs synthesized suggest that cell phenotype can change,[27] possibly in response to altered matrix stress distributions (Figure 3).

With increasing age, the hydrostatic nucleus becomes smaller and decompressed, and so more of the compressive load-bearing is taken by the anulus (Figure 3B).[42] To fulfill this functional demand, the inner anulus of the young adult possesses a relatively high proteoglycan content.[21] However, with increasing age, the proteoglycan content decreases, and the anulus becomes stiffer and weaker.[43] Disc height does not show a major decrease with age,[44] although degenerative changes can cause the anulus to collapse in some old discs (see later).


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