The pathogenesis of osteoarthritis in cerebral palsy
DENNIS R CARTER PHD1,2| | BRIAN TSE BSE3
1 Bone and Joint Center of Excellence, VA Palo Alto Health Care System, Palo Alto, CA, USA.| |2 Department of Mechanical Engineering, Stanford University,
Stanford, CA, USA.| |3 Biomechanical Engineering Program, Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
Correspondence to Dennis R Carter, Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA. E-mail: email@example.com
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
The morphogenesis, remodeling, and degeneration of diarthroidial joints are
directly under the control of the loading histories created by the musculoskeletal
system during development and aging. The altered loading histories in
individuals with cerebral palsy (CP) lead to aberrations in joint morphogenesis
and an acceleration of joint degeneration. To understand this process in the hip,
the normal ontogeny of the hip joint is reviewed with special attention to the
mechano-biological factors associated with joint morphogenesis, endochondral
ossification, and cartilage degeneration. A contrast is then made with the
mechano-biological alterations observed with CP and the consequent influence
on joint destruction. The features of the pathogenesis are: (1) altered muscular
activity and restricted range of motion result in abnormal joint morphology,
subluxation, and poor coverage of the femoral head; (2) joint incongruities
created in early development cause local stress concentrations that can
mechanically damage the articular cartilage; (3) the reduced magnitudes of
muscular forces reduce the contact pressures at the joints, creating thinner
cartilage and osteopenia; and (4) the thinner cartilage degenerates early, and
subchondral bone collapse further contributes to the mechanical destruction
of the remaining cartilage.
Cerebral palsy (CP) is a non-progressive neurological
disorder in which the afflicted individual loses a certain
degree of control over his or her muscles at an early
age. People with CP have a wide range of conditions
and skeletal problems, such as crouched gait, tightness
in muscles, abnormal bone development, low bone
density, impaired vision, and malnutrition. In addition,
osteoarthritis arises prematurely and more often in
patients with CP than in other individuals. Boldingh
et al.1studied 140 patients with CP ranging from 16 to
84 years of age and reported that 59% of them had
osteoarthritis. Another study reported osteoarthritis in
27% of participants between the age of 15 and 25 years.
2Both studies reported a higher prevalence of osteoar-
thritis than normal for each age group. Although many
anecdotal observations of the occurrence of osteoar-
thritis of the hip joint in patients with CP have been
made from surgical exposure and radiological evidence,
no study has specifically detailed this correlation or the
reasons behind it.
NORMAL BONE AND JOINT DEVELOPMENT
To evaluate the effects of CP on osteoarthritis, one must
appreciate the normal development of bone and cartilage.
Bone growth and maintenance is a dynamic process that is
regulated by biological and mechanical factors. Skeletal
development begins in utero and is directed by the differ-
entiation of mesenchymal stem cells into different cell or
tissue types, including the cartilage anlagen or rudiments
that serve as templates for the skeleton that later forms.3
Eventually, the cartilage rudiments undergo endochondral
and periosteal ossification to create bones. This growth
and ossification are under the direct control of local
mechanical-loading conditions created by muscular activ-
ity, which influences local gene expression.3
Articular cartilage is the hyaline cartilage at the end of
long bones that facilitates smooth articulation of joints. It
is the remaining part of the cartilage rudiment that has not
undergone ossification. The preservation of articular carti-
lage is regulated by the various stresses and strains acting
on it. Hydrostatic pressure on the cartilage promotes
ª 2009 Mac Keith Press No claim to original government works Developmental Medicine & Child Neurology 2009, 51 (Suppl. 4): 79–83
DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY REVIEW
extracellular matrix production (aggrecan and collagen II)
and inhibits cell hypertrophy. These factors slow ossifica-
tion and maintain articular cartilage. Therefore, joint areas
experiencing high forces have the thickest articular carti-
lage (Fig. 1).
PATHOGENESIS OF IDIOPATHIC OSTEOARTHRITIS
Osteoarthritis is the destruction of the articular cartilage
found at the joints of bones such as the hip. Osteoar-
thritis is most often associated with aging, where over
time, the quiescent subchondral growth front slowly
drifts toward the joint surface, thereby thinning the car-
tilage (Fig. 2a).4Eventually the thinning articular carti-
lage loses its mechanical integrity and begins to wear
away. As a result, people who suffer from osteoarthritis
experience pain and inflammation at the joints when
they move. However, the normally slow subchondral
endochondral ossification and the subsequent mechanical
destruction with aging are not the only mechanisms that
can cause osteoarthritis. The degradation of cartilage
can be accelerated by several other factors, including
impact, and joint laxity, which accentuates mechanical
destruction of the articular cartilage.3
The process of subchondral endochondral ossification
with aging can be accelerated by the lack of mechanical
joint pressure. Joint loading creates hydrostatic pressure in
the cartilage, which is chondroprotective.5With improper
or reduced loading of the joints, some areas of cartilage
experience low hydrostatic pressure, which promotes
endochondral ossification (Fig. 1).5
Figure 1: The shaded areas show the areas of initial degeneration in
osteoarthritis. The stippled surfaces represent areas of surface con-
tact, and the larger dots show areas of greater and more frequent
contact pressure. Areas of no contact pressure develop osteoarthritis
first because of subchondral endochondral ossification (source: Mos-
kowitz et al13).
Figure 2: These figures show the effects of the two mechanisms of osteoarthritis. (a) Photomicrograph of the articular surface in an arthritic joint.
The cartilage is thinning as the tidemark, which is the interface between cartilage and calcified cartilage, advances toward the joint surface, illus-
trating subchondral endochondral ossification (source: Bulough15). (b,c) These figures show the destruction caused by surface wear and fibrillation
(source: Harrison et al.15).
Developmental Medicine & Child Neurology 2009, 51 (Suppl. 4): 79–83
Another mechanism of cartilage destruction is surface
wearorfibrillationofthearticularcartilage (Fig.2b, c).The
cartilage tissue can be mechanically worn away by forces
that rip or tear away pieces of cartilage. This mechanical
degradation can occur rapidly and is accelerated by shear
EFFECTS OF CP ON JOINT DEVELOPMENT AND
People with CP develop a wide range of skeletal defor-
mities shortly after birth. The more severe deformities
include acetabular malformations, hip subluxation and dis-
location, elevation of the tibial tubercle, fragmentation of
the patella, increased femoral anteversion in the proximal
femur, tibial torsion, and differing rates of skeletal matura-
tion.6–8Most of these changes are gradual and are caused
by a multitude of factors ranging from abnormal joint
forces to muscle imbalance caused by muscular spasticity.
Individuals with more severe cases of CP tend to develop
osteoarthritis at a higher rate than those with less severe
disease.2The level of motor disability varies, but people
with quadriplegical and diplegical are known to be more
susceptible to osteoarthritis. The main reason is that their
compromised ambulation, and their reduced muscular
activity, as well as their restricted range of motion, is
unable to provide sufficient cyclic loads to different areas
of the hip that are necessary to maintain the cartilage. This
promotes the development of osteopenia and accelerates
subchondral endochondral ossification, making the carti-
Subluxation and dislocation of the femoral head is a
major feature of CP that contributes to osteoarthritis.
Lundy et al.6and Gamble et al.9found that dislocations
were more likely to be found in non-ambulators who are
neurologically immature. Physiologically, the adductor,
internal rotator, and hip-flexor muscle groups overpower
their antagonistic groups and change the functional axis of
the femur to the lesser trochanter.8,9These forces create
an imbalance of the hip and direct the head superolaterally,
gradually causing it to subluxate and eventually dislocate.
Subluxation comes with different degrees of gross and
microscopic changes for the hip, such as deformation to
the femoral head and an irregular physis.
The degeneration of the articular cartilage around the
femoral head in patients with CP can be observed radio-
graphically as well as by direct visualization during sur-
geries and autopsies of individuals with dislocated hips.
The subluxation of the femoral head and the consequent
morphological changes of the hip provide the mechanisms
for osteoarthritis.10It causes deformation of the femoral
head with the flattening of the medial side of the epiphysis,
causing the femoral head to have a wedge shape (Fig. 3).6
Moreover, a stress concentration created by the acetabular
labrum can appear in the femoral head superolaterally and
Figure 3: A view of the dissection of a right hip of a 12-year-old male with severe cerebral palsy. (a) A view of the hip internally rotated; (b) A view
of it externally rotated. This view shows that the hip is beginning to subluxate from the acetabulum during external rotation. The arrow points to the
early indentation of the femoral head. This view also shows the extent of the uncovered portion of the femoral head that is not directly loaded,
causing it to be more susceptible to osteoarthritis through subchondral endochondral ossification (source: Lundy et al6).
Osteoarthritis and CP Dennis R Carter and Brian Tse
create a deep notch in the cartilage (Fig. 4).6This joint
incongruity is a region of high stress that leaves the other
parts of the femoral head with a reduced load. Areas of
reduced loading are susceptible to osteoarthritis by under-
going the final stages of subchondral endochondral ossifi-
cation. This is usually found on the medial side of the
femur. On the other hand, even though high hydrostatic
pressure is known to be chondro-protective, focal shear
stresses are created in the notch where the head articulates
against the acetabular labrum.8Shear stresses are particu-
larly damaging to the articular cartilage, and this region
experiences wear and fibrillation.
Another common compounding problem found in
those with CP is diminished bone mineral density (BMD).
The pathogenesis of low BMD is complex, but it is caused
primarily by low joint forces.11,12Osteopenia and low
BMD contribute to subchondral bone collapse and defor-
mation of the femoral head. This malformation increases
joint incongruity, further contributing to the mechanical
damage of the articular cartilage.6
The abnormal loading conditions in CP lead to abnormal
joint morphology and cause a cascade of events that lead to
early osteoarthritis. This osteoarthritic cascade has four
main features: (1) Altered muscular activity and restricted
range of motion result in abnormal joint morphology, sub-
luxation, and poor coverage of the femoral head. (2) Joint
incongruities created in early development cause local
stress concentrations that can mechanically damage the
articular cartilage. (3) The reduced magnitudes of muscu-
lar forces reduce the contact pressures at the joints, creat-
ing thinner cartilage and osteopenia. (4) The thinner
cartilage degenerates early, and subchondral bone collapse
further contributes to the mechanical destruction of the
Figure 4: Figures a, b, and c show the progressive stages of degeneration through radiographs of three femurs cut in the coronal plane. Notice the
deformation of the femoral head in all three cases. (a) There is a slight cupping, or notch, in the superolateral aspect of the epiphysis. (b) The lateral
aspect of this femoral head shows a deep concave cut on, and sharp, pointed surface on, the superior aspect. (c) Extensive articular destruction is
seen in addition to a collapse of the subchondral and trabecular bone structure. Joint incongruities contribute to mechanical destruction of the
cartilage in the regions of contact (source: Lundy et al.6).
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