Low back pain is a major public health problem in our society and the cause of significant morbidity. The prevalence is high: It has been documented that 80% to 90% of the population has suffered from low back pain once in their lives (1). Back disorders occupy the highest rank of musculoskeletal disability pension among the Swiss male population (2), and data from a survey of the Swiss population reported that 10% of those interviewed had suffered severe low back pain in the previous 4 weeks (3). It not only accounts for much suffering and distress to patients and their families but also puts an enormous economic burden on society. The societal costs, including direct medical costs, insurance, lost production and disability benefits, are estimated at £12 billion per year in the United Kingdom, and more than $50 billion in annual health costs in the United States can be related directly or indirectly to this disease (4).

Although the etiologies are many, intervertebral disc degeneration appears to be the leading cause for chronic axial low back pain (5,6). The incidence of disc degeneration is rising exponentially with current demographic changes and an increased aged population. Around 10% of 50-year-old discs and 60% of 70-year-old discs are severely degenerate (7).

The intervertebral discs transmit loads arising from body weight and muscle activity through the spinal column, while also maintaining flexibility and allowing bending, flexion, and torsion of the spinal column.

The intervertebral discs are complex structures consisting of an outer ring of fibrous cartilage termed annulus fibrosus, which surrounds a more gelatinous core known as nucleus pulposus. The central nucleus pulposus contains randomly organized collagen fibers and radially oriented elastin fibers (8,9) embedded in a highly hydrated aggrecan-containing gel-like matrix (10,11). The annulus fibrosus consists of a series of concentric rings, or lamellae with collagen fibers lying parallel within each lamella (12,13).

Throughout growth and skeletal maturation, the boundary between annulus and nucleus becomes less obvious, and with increasing age the nucleus generally becomes more fibrotic and less gel-like (7,14,15). The disc changes in morphology, becoming more and more disorganized. The degenerative changes, whose incidence increase with age, also include cell death, changes in cell proliferation, mucous degeneration, granular changes, and concentric tears. Apoptosis appears to play a prominent role in age-related degeneration, with higher rates of apoptosis present in older individuals (16). In addition, degenerative discs produce a multitude of inflammatory, degradative, and catabolic molecules, including proteolytic enzymes, oxygen-free radicals, nitric oxide, interleukins, and prostaglandins (17,18,19). In particular, cathepsin, lysozyme, aggrecanases and several matrix metalloproteinases (MMPs) are thought to play a role in disc degeneration. Compared to normal discs, elevated levels of MMP-1, MMP-2, MMP-3, MMP-9, and lysozyme have been observed in degenerate discs (20,21,22,23,24).

The most significant biochemical change to occur in disc degeneration is loss of proteoglycan (11,14). The aggrecan molecules become degraded, with smaller fragments being able to leach from the tissue more readily than larger fractions (23). This results in loss of glycosaminoglycans, which has a major effect on the load-bearing behavior of the disc. With loss of proteoglycan, the osmotic pressure of the disc falls and the disc is less able to maintain hydration under load (11). Loading may thus lead to inappropriate stress concentrations along the vertebral endplate or in the annulus, which has been associated with disc-related pain (25).

Findings from epidemiologic and genetic studies point to the multifactorial nature of disc degeneration (26). One of the primary causes of disc degeneration is thought to be failure of the nutrient supply to the disc cells (27,28). The diffusion capacity of even the healthy disc is relatively poor, and it is further limited by aging and degenerative changes of the endplate tissue (29,30). Abnormal mechanical loads are also believed to cause damage to the disc and finally clinical symptoms and back pain (31). It is also evident that mutations in several different classes of genes may cause the changes in matrix morphology, disc biochemistry, and disc function associated with disc degeneration (32,33,34).

Current treatments attempt to reduce pain rather than repair the degenerated disc. They range from analgesia, the use of muscle relaxants, and injection of corticosteroids or local anesthetics to manipulation therapies. The degenerative disorders of the lumbar spine that require surgical intervention include herniated discs, spinal stenosis, degenerative spondylolisthesis, degenerative scoliosis, and degenerative disc disease. The most controversial among them is the treatment of idiopathic low back pain associated with lumbar degenerative disc disease, which remains a challenge for the orthopaedic surgeon. Surgical procedures involving vertebral fusion produce a relatively good short-term clinical result in relieving pain, but they alter the biomechanics of the spine and can lead to further degeneration of the discs at adjacent levels. In fact, the failure rate for lumbar fusions is estimated to be in the 20% to 40% range (35), and there is clinical and radiologic evidence that spinal fusion leads to accelerated degeneration of the adjacent motion segment (36,37). More recently, there has been an increasing interest in disc arthroplasty that can maintain motion of the intervertebral segment. The efficacy of arthroplasty, however, remains controversial, and none of the current artificial disc replacement designs fully replicate normal disc biomechanics.

In general, surgical procedures try to remove rather than repair the problems associated with the degenerate intervertebral disc. Repair is, however, the ideal therapeutic approach as it restores the normal structure and function of the intervertebral disc. We believe that future treatments will be able to effect biologic repair of the damaged tissue by restoring it to a tissue of similar functional competence to the healthy native one.

Realistically, only two biologic approaches to the treatment of disc degeneration are likely to become clinically available within the next 10 years. At the earlier stage of disc degeneration, injection of inhibitors of proteolytic enzymes or cytokines or biologic factors that stimulate cell metabolic activity (i.e., growth factors) can be foreseen, to slow down the degenerative process (38,39,40).