What is the etiology of Intervertebral Disc Syndrome (IVDS)?

From the Guidelines

Intervertebral disc disease (IVDS) is primarily caused by degenerative changes in the intervertebral discs that occur with aging, genetic predisposition, and mechanical stress, as supported by the most recent study from 2021 1. The etiology of IVDS involves a complex interplay of factors that lead to disc degeneration, including genetic factors, mechanical stress, and decreased nutrient supply to the disc.

• Normal discs contain a gelatinous nucleus pulposus surrounded by a fibrous annulus fibrosus, but with age, the nucleus pulposus loses water content and proteoglycans, becoming less elastic and more fibrous.
• Genetic factors play a significant role, with studies showing heritability of 65-80% for disc degeneration, as noted in previous studies 1.
• Mechanical factors such as repetitive loading, occupational stresses, and trauma contribute to accelerated degeneration, as described in the American College of Physicians and the American Pain Society guidelines 1.
• Certain breeds of dogs, particularly chondrodystrophic breeds like Dachshunds and Beagles, have a genetic predisposition to early disc degeneration, but in humans, obesity, smoking, and poor posture are additional risk factors. The degenerative process involves decreased nutrient supply to the disc, accumulation of degradation products, and an imbalance between matrix synthesis and breakdown mediated by inflammatory cytokines and matrix metalloproteinases, ultimately leading to structural failure that can manifest as disc herniation, bulging, or complete rupture, resulting in compression of neural structures and clinical symptoms, as discussed in the 2021 update of the ACR Appropriateness Criteria 1.
• The most common cause of cauda equina syndrome, a serious complication of IVDS, is lumbar disc herniation at the L4-L5 and L5-S1 levels, as noted in the 2021 study 1.
• MRI is the imaging study of choice in the evaluation of suspected cauda equina syndrome, multifocal deficit, or progressive neurologic deficit, due to its ability to accurately depict soft-tissue pathology, assess vertebral marrow, and assess the spinal canal patency, as recommended in the 2021 guidelines 1.

From the Research

IVDS Etiology

The etiology of intervertebral disc degeneration (IVDD) is complex and multifactorial, involving various factors such as:

• Genetic factors, including mutations in structural proteins and enzymes involved in the immune response 2
• Aging, which can lead to the senescence and apoptosis of nucleus pulposus cells (NPCs) and the progressive degeneration of extracellular matrix (ECM) 3
• Mechanical injury, which can disrupt the homeostasis maintained by the structures of the intervertebral disc (IVD) 4
• Malnutrition, which can impair cell metabolism due to pH alteration and poor nutrition, leading to autophagy and disruption of the homeostasis within the IVD 4
• Autoimmune damage, which is considered a promising hypothesis for the pathogenesis of IVDD 2

Risk Factors

Several risk factors can contribute to the development of IVDD, including:

• Genetic factors, which can affect the course of the disease 2
• Mechanical damage, which can be considered a risk factor for IVDD 2
• Environmental factors, which can accelerate the progression of the disease 4

Pathogenesis

The pathogenesis of IVDD is a complex multifactorial process without an evident starting point, involving:

• The disruption of the homeostasis maintained by the structures of the IVD 4
• The imbalance between catabolic and anabolic processes in the intervertebral discs 5
• The degradation of extracellular matrix, neoinnervation, and neovascularization 5
• The inflammatory response and fibrosis of annulus fibrosus (AF) 3