OPBSPathologyMusculoskeletal
Must Know
- Lumbar spondylosis is degeneration of the discs, vertebral bodies and facet joints, diagnosed mainly on radiographs.
- Spondylosis is described as osteoarthritis of the spine, with disc degeneration and osteophytes at the same level.
- Disc space narrowing brings adjacent pedicles closer and reduces the superior to inferior height of the foramen.
- The spine has 23 intervertebral discs, enlarging from cervical to lumbar levels.
- Cartilage end plates are a thin hyaline cartilage layer between disc and vertebra.
- Disc degeneration begins in the extracellular matrix of the nucleus pulposus.
- The earliest matrix change is proteolytic breakdown of aggrecan with buildup of degraded proteoglycan.
Disc Structure
| Feature | Nucleus pulposus | Annulus fibrosus |
|---|---|---|
| Proteoglycan and water | High | Low |
| Collagen type | Loose type II network | Mainly type I, some type II |
| Fibre arrangement | Random | 20 to 25 concentric lamellae, alternating direction |
| Resists | Axial compression | Tension in bending and twisting |
- Water and proteoglycan rise from annulus to nucleus. Collagen falls from outer annulus to nucleus.
- Nuclear proteoglycan and water fall with age.
- Nuclear collagen is highest in cervical discs and lowest in lumbar discs. Proteoglycan shows the reverse.
- Aggrecan is the most abundant nuclear proteoglycan, carrying chondroitin sulfate and keratan sulfate on one core protein.
- Aggrecan binds hyaluronan to form aggregates.
- Negatively charged proteoglycans draw in water, producing osmotic swelling and hydrostatic pressure. Collagen resists the swelling.
| Matrix component | Change with age |
|---|---|
| Hyaluronan | Rises |
| Link protein | Falls, with more proteolysis |
| Fibronectin | Rises, with more fragmentation |
| Proteoglycan and water in nucleus | Fall |
More on disc matrix
- Fibronectin fragments are thought to drive catabolic events in degeneration.
- Elastin makes up about 2 percent of annular dry weight. Its part in degeneration is unclear.
- Disc cells maintain homeostasis by making proteoglycan and collagen.
- The cause of hyaluronan accumulation with age is not understood.
Disc Degeneration
- Nutrients come mainly from vessels at the disc end plate interface, diffusing through the cartilage end plate.
- Falling nutrient supply reduces cell viability and macromolecule synthesis.
- End plate calcification lowers porosity and vascularity, raising lactate and lowering pH, then causing cell apoptosis.
- Prolonged underloading, overloading and static loading all promote matrix damage.
- Short chondroitin sulfate alleles of the aggrecan gene are linked to early degeneration.
- Small annular tears join into radial tears, allowing protrusion, desiccation and height loss.
- IL-1 and TNF-α rise progressively in degenerating discs.
- TNF-α lowers aggrecan and type II collagen gene expression and raises MMP and ADAMTS expression.
- MMPs degrade collagen, aggrecan and link protein. ADAMTS-4 and ADAMTS-5 are aggrecanases.
- Collagen cross-linking rises through nonenzymatic glycation and lipid peroxidation.
More on the degenerative cascade
- Cell changes include senescence with altered gene expression and apoptosis.
- Thinning or microfracture of the end plate raises permeability, giving uneven load transfer and focal shear stress.
- As peripheral blood supply declines, waste and degraded matrix accumulate and central water falls.
- As hydration falls the nucleus solidifies and disc height drops.
Facet Joints and Osteophytes
- Facet joints are true synovial joints. The disc is a fibrocartilaginous joint.
- One disc plus two facet joints form the three-joint complex, or motion segment.
- Lumbar facets lie nearly vertical in the sagittal plane, limiting rotation and forward slip.
- Facet arthritis can occur without disc degeneration.
- Early facet changes affect cartilage, synovium and capsule. Subchondral bone changes come later.
- Cartilage shows fibrillation and pitting, then fissuring, then erosion to bone, with chondrocyte clustering.
- Osteophytes arise from periosteum by endochondral ossification.
- Disc space narrowing correlates strongly with osteophyte formation.
- Anterior vertebral osteophytes form late, possibly to stabilise an unstable column.
Inflammatory Mediators
| Mediator | Action |
|---|---|
| Phospholipase A2 | Mechanical hyperalgesia |
| Nitric oxide | Inhibits mechanical hyperalgesia, produces thermal hyperalgesia |
| IL-1, TNF-α, PGE2 | Matrix degradation, more MMPs |
| IL-6 | Induces TIMP-1 |
| TIMP-1 | Inhibits MMPs |
| TGF-β superfamily | Blocks MMP synthesis |
| IGF-I, PDGF | Antiapoptotic |
| CGRP, glutamate, substance P | Modulate dorsal root ganglion |
- IL-6 from facet synovium and cartilage is raised mainly in spinal stenosis.
- IL-1β is higher in stenosis than in disc herniation and links most with leg pain.
- IL-1β stimulates MMP production.
- HMW adiponectin is proinflammatory. LMW adiponectin is anti-inflammatory.
More on adiponectin and IL-1β
- Adiponectin can raise MMPs and inducible nitric oxide synthase.
- One study found greater adiponectin expression in facet arthritis than IL-1β or TNF-α.
- In herniated disc cells IL-1β drives its own production, raising IL-6, COX-2, MMP-1 and MMP-3.
- MMP-2 and MMP-9 are gelatinases. MMP-1 is collagenase-1. MMP-3 is stromelysin-1.
Radiculopathy
- Compression comes from disc herniation, thick ligamentum flavum, facet arthritis and osteophytes.
- Spinal nerve roots are more vulnerable to compression than peripheral nerves.
- Dorsal root ganglia are highly sensitive to compression and hypoxia.
- Compression causes intraneural oedema, demyelination and fibrosis.
- Vascular permeability rises more with rapid onset compression than slow onset.
- Sustained compression leads to Wallerian degeneration.
- Macrophages are the principal cells starting and sustaining inflammatory neuritis.
- TNF-α is a main driver, upregulating IL-1β and IL-6 in ganglion, Schwann, perineurial and endothelial cells.
Numbers to Remember
- Spondylosis prevalence. 40 to 85 percent.
- Discs. 23, making up 20 to 30 percent of spinal length.
- Annular lamellae. 20 to 25.
- Facet pain. 5 to 15 percent of chronic axial low back pain.
- Radiculopathy prevalence. 2 to 43 percent.
Memory Aids
- Nucleus squashes, annulus twists. Nucleus resists compression, annulus resists tension in bending and torsion.
- TIMP tames MMP. IL-6 induces TIMP-1, which inhibits MMPs.
Exam Traps
- The annulus is mainly type I collagen. The nucleus is type II.
- Hyaluronan rises with age while link protein falls.
- Nitric oxide inhibits mechanical hyperalgesia but produces thermal hyperalgesia.
- Facet arthritis does not need prior disc degeneration.
Related pages. Discogenic Back Pain, Lumbar Disc Prolapse, Lumbar Canal Stenosis, Cervical Spondylosis, Cervical Radiculopathy, Spondylolysis and Spondylolisthesis
Source
Webb BA, Fischgrund JS, Khalil JG. Lumbar Spondylosis, Degenerative Disk Disease, and Radiculopathy. In. Aaron RK, editor. Orthopaedic Basic Science. Foundations of Clinical Practice. 5th ed. Philadelphia, Wolters Kluwer, 2021.
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Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 17 October 2026.