Pathogenesis
The high incidence of simultaneous degenerative changes
to the intervertebral disk, vertebral body, and associated
joints suggests a progressive and dynamic mechanism, with
interdependent changes occurring secondary to disk space
narrowing [17].
Intervertebral disks are believed to undergo what Kirkaldy
Willis and Bernard [24] first coined a ‘‘degenerative
cascade’’ (Fig. 1) of three overlapping phases that may
occur over the course of decades. Phase I (Dysfunction
Phase) describes the initial effects of repetitive microtrauma
with the development of circumferential painful
tears of the outer, innervated anulus, and associated endplate
separation that may compromise disk nutritional
supply and waste removal. Such tears may coalesce to
become radial tears, more prone to protrusion, and impact
the disk’s capacity to maintain water, resulting in desiccation
and reduced disk height. Fissures may become
ingrown by vascular tissue and nerve endings, increasing
innervation and the disk’s capacity for pain signal transmission
[25]. Phase II (Instability Phase) is characterized
by the loss of mechanical integrity, with progressive disk
changes of resorption, internal disruption, and additional
annular tears, combined with further facet degeneration
that may induce subluxation and instability. During Phase
III (Stabilization Phase), continued disk space narrowing
and fibrosis occurs along with the formation of osteophytes
and transdiscal bridging [26].
Schneck presents a further mechanical progression,
building upon this degenerative cascade of the intervertebral
disk, to explain other degenerative changes of the axial
spine. He proposes several implications of disk space
narrowing. Adjacent pedicles approximate with a narrowing
of the superior–inferior dimension of the intervertebral
canal. Laxity due to modest redundancy of the longitudinal
ligaments enables bulging of the ligamentum flavum and
potential for spine instability. Increased spine movement
permits subluxation of the superior articular process (SAP),
causing a narrowed anteroposterior dimension of the
intervertebral and upper nerve root canals. Laxity may also
translate into altered weight mechanisms and pressure
relationships on vertebral bone and joint spaces believed to
influence osteophyte formation and facet hypertrophy to
both inferior and superior articular processes with risks for
projection into the intervertebral canal and central canal,
respectively. Oblique orientations of the articular processes
may further cause retrospondylolisthesis, with resulting
anterior encroachment of the spinal canal, nerve root canal,
and intervertebral canal [17].
Biochemical research exploring osteophyte formation
supports the above process. Osteophyte lipping is believed
to form at periosteum [27] through the proliferation of
peripheral articular cartilage which subsequently undergoes
endochondral calcification and ossification [28].
Changing weight mechanics and pressure forces as well
as alterations in oxygen tension and dynamic fluid pressure
appear to be influential factors in osteophyte
formation [14]. Mesenchymal stem cells of the synovium
or periostium are likely precursors, with synovial macrophages
and a milieu of growth factors and extracellular
matrix molecules acting as probable mediators in this
process [29