Overview: Degenerative Disc Disease
DDD is a condition characterized by age-related changes to the intervertebral discs, the gel-like cushions that separate vertebrae. Over time, these discs become less flexible and less able to cushion the spine. This can result in pain and stiffness in the neck and/or back, as well as pain that spreads to the back of the head, trunk, shoulders, arms, hands, legs, and feet.1
- DDD is a natural process of aging, and most people develop some degree of the condition over time. Pain and limited mobility associated with DDD is the most common physical impairment affecting otherwise healthy young and middle-aged adults.2
- It is estimated that as many as 80 percent of all adults experience back pain at some point during their lifetime, the chief cause of which is DDD.2,3
- Globally, back pain is the leading cause of disability with 651 million people affected worldwide.4 The annual cost of back pain in the US is estimated to be as high as $500 billion.5
Recent studies have shown that the Wnt pathway may be involved in the disease processes of DDD. Elevated levels of β-catenin, a central component of the pathway, have been observed in discs of patients with DDD, indicating increased Wnt signaling.6
- This increase in Wnt signaling triggers the production of enzymes that break down the intervertebral extracellular matrix and promote disc degradation.6
- As shown by in vitro studies, Wnt signaling also inhibits the proliferation of nucleus pulposus cells, which reside in the disc and are responsible for providing cushioning to the joint.7,8
- These lines of evidence suggest that targeted inhibition of the Wnt pathway might preserve disc integrity and potentially lead to disc regeneration in patients with DDD.
- Vergroesen PP, Kingma I, Emanuel KS, et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis Cartilage. 2015;23:1057-70.
- Anderson GBJ. Epidemiological features of chronic low back pain. Lancet. 1999;351:581-5.
- Wang HG, Samartzis D. Clarifying the nomenclature of intervertebral disc degeneration and displacement: from the bench to bedside. Int J Exp Pathol. 2014;7:1293-8.
- Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:743-800.
- Dagenais S, Tricco AC, Haldeman S. Synthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelines. Spine J. 2010;10:514-29.
- Wang M, Tang D, Shu B, et al. Conditional activation of β-catenin signaling leads to severe defects in intervertebral disc tissue. Arthritis Rheum. 2012;64:2611-23.
- Hiyama A, Sakai D, Risbud MV, et al. Enhancement of intervertebral disc cell senescence by WNT/β-catenin signaling-induced matrix metalloproteinase expression. Arthritis Rheum. 2010;62:3036-47.
- Colombier P, Clouet J, Hamel O, et al. The lumbar intervertebral disc: from embryonic development to degeneration. Joint Bone Spine. 2014;81:125-9.