Knee Kinematics, Cartilage Morphology,

and Osteoarthritis after ACL Injury

CLINICAL SCIENCES
AJIT M. W. CHAUDHARI1, PAUL L. BRIANT2,3, SCOTT L. BEVILL2, SEUNGBUM KOO2,
and THOMAS P. ANDRIACCHI2,3,4
1
Department of Orthopaedics, Ohio State University, Columbus, OH; 2Department of Mechanical Engineering,
Stanford University, Stanford, CA; 3Bone and Joint Center, VA Palo Alto Health System, Palo Alto, CA;
and 4Department of Orthopaedic Surgery, Stanford University, Stanford, CA

ABSTRACT
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CHAUDHARI, A. M. W., P. L. BRIANT, S. L. BEVILL, S. KOO, and T. P. ANDRIACCHI. Knee Kinematics, Cartilage Morphology,
and Osteoarthritis after ACL Injury. Med. Sci. Sports Exerc., Vol. 40, No. 2, pp. 215–222, 2008. This review examines a mechanism for
the initiation of osteoarthritis after anterior cruciate ligament (ACL) injury by considering the relationship between reported ambulatory
changes after ACL injury, cartilage adaptation to load, and the association between cartilage loads during walking and regional
variations in cartilage structure and biology. Taken together, these observations suggest that cartilage degeneration after ACL injury
could be caused by a kinematic gait change that shifts ambulatory loading applied to cartilage. Such a shift may cause regions of
cartilage to become newly loaded, be subjected to altered levels of compression and tension, or become unloaded. The metabolic
sensitivity of chondrocytes to such changes in their mechanical environment, combined with the low adaptation potential of mature
cartilage, could lead to cartilage degeneration and premature osteoarthritis after ACL injury. This proposed mechanism demonstrates the
value of using the ACL injury model to understand the relationship between mechanics and biology, as well as helping to explain the
importance of restoring normal ambulatory kinematics after ACL injury to avoid premature osteoarthritis. Key Words: REVIEW,
KNEE, KINEMATICS, CARTILAGE METABOLISM, BIOMECHANICS, CARTILAGE HISTOLOGY

O
steoarthritis (OA) of the knee occurs in a sub-
stantial portion of the population over the age of 50
(26); however, there is limited information on the
underlying causes of knee OA. One subgroup at consid-
erably elevated risk of knee OA consists of individuals who
have suffered complete rupture of the anterior cruciate
ligament (ACL). ACL rupture is an injury that most often
occurs during sports and to a younger population (8,11,50),
but it results in a much greater reported likelihood of
developing knee OA, as well as of developing OA, at a
younger age (17,35,47,48,67). For example, in a population
of female soccer players who suffered ACL ruptures at an
average age of 19 yr, Lohmander et al. (47) found that 51%
of the injured knees showed radiographic knee OA just 12
yr after injury (at age 31), compared with only 7% of the
uninjured contralateral knees. ACL rupture creates the
potential for altered structural properties of the joint, altered
joint kinematics during in vivo motion, and altered bio-
logical activity, making the ACL-injured knee a valuable
test model for understanding the interrelationship between
mechanical and biological factors and their roles in the
initiation of knee OA.
In the ACL-injured patient, abnormal motion is observed
immediately (3,30,42), whereas degenerative changes in
the cartilage are only observed many years later
(17,35,47,48,67). It has been suggested (4–6) that abnormal
kinematics associated with ACL deficiency could be a cause
of these degenerative changes by causing joint loads to be
shifted to infrequently loaded areas of the cartilage and away
from frequently loaded areas of the cartilage. The purpose of
this review is to further explore a kinematic basis for the
premature initiation of OA in the context of reported
kinematic changes relative to the structural and biological
variations of articular cartilage.

ALTERATIONS IN KNEE MOTION AFTER

ACL INJURY
Address for correspondence: Ajit M. W. Chaudhari, Ph.D., OSU Sports
Medicine Center, 2050 Kenny Rd, Suite 3100, Columbus, OH 43221;
The ACL plays an important role in the kinematics of the
E-mail: chaudhari.2@osu.edu. tibiofemoral joint, by providing both anterior-posterior
Submitted for publication April 2007. translational and internal-external rotational stability. It has
Accepted for publication July 2007. been reported that there are significant differences in the
0195-9131/08/4002-0215/0 tibiofemoral motion of ACL-deficient knees during walking
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ with respect to uninjured contralateral knees or healthy con-
Copyright Ó 2008 by the American College of Sports Medicine trols (3,30). One study examining the 6-degree-of-freedom
DOI: 10.1249/mss.0b013e31815cbb0e motion of the knee during the stance phase of walking

215

Copyright @ 2008 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.

CLINICAL SCIENCES
FIGURE 1VTypical tibial internal-external rotation during walking
in an ACL-deficient (ACLD) patient. On average, the ACLD tibia
maintains an offset toward a more internally rotated position during
stance than the contralateral tibia. Modified from Andriacchi et al. (6),
with permission.
observed offsets towards internal tibial rotation (Fig. 1)
and posterior tibial translation, meaning that the tibia of
ACL-deficient knees maintained a position of greater internal
rotation and posterior translation throughout stance when
compared with the contralateral side (3). Other studies have
used multiview radiographic techniques to observe tibiofe-
moral motion, which offer significantly improved accuracy
although they do not permit subjects to perform the most
common daily activity of walking because of their small
imaging volumes. Studies of ACL-deficient knees using
biplanar fluoroscopy have shown impingement of the medial
tibial spine by the medial femoral condyle (42) as well as
internal tibial rotation at low flexion angles (19) during a
quasi-static lunging activity. After ACL reconstruction, a
study using biplanar high-speed radiography showed that
ACL-reconstructed knees maintained a position of greater
external rotation throughout stance when compared with
the contralateral side during downhill running (61). This
result suggests that ACL-reconstructed knees may retain
an elevated risk of OA similar to ACL-deficient knees
(47) because of kinematic abnormalities in tibiofemoral
motion.
Other studies have observed altered tibiofemoral motion
using magnetic resonance imaging (MRI) while in different
flexion-extension positions, either in quasi-static positions
(46,56) or during limited flexion-extension under constant
load (9). Because of the way MR images are obtained,
dynamic MRI also requires the averaging of many tens or
hundreds of cycles of the activity (9). These studies have
found altered tibiofemoral contact patterns (56), more
anterior tibial translation (9), and altered tibial internal-
external rotation (9,46) in ACL-deficient knees relative to
healthy contralateral knees.
Although the above mentioned studies used different
methods to capture motion and studied different activities,
all agree that tibiofemoral motion is altered after ACL
216 Official Journal of the American College of Sports Medicine
Copyright @ 2008 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
injury. The differences in specific changes in joint kine-
matics are most likely attributable to the different activities
examined. As OA is thought to be a gradual degenerative
process attributable to an accumulation of mechanical and
biological changes over time (5), walking may be the most
relevant activity to understanding OA initiation and
progression. A detailed discussion of the implications of
using different motion capture methods for understanding
the relationship between ambulatory mechanics and knee
OA has been previously reported (5).
Animal models of OA after ACL transection also support
the importance of altered joint motion as a component of the
initiation of OA. In biplanar radiography and video-based
motion analysis studies, it has been observed that canine
tibiofemoral kinematics are altered after ACL transection
(60,66). The feline ACL transection model also shows
altered kinematics, muscle activations, and loading relative
to sham-operated animals (32). The long-term consequences
of these ACL transection surgeries are similar to ACL injury
in humans, with loss of proteoglycan content (45), changes in
matrix metalloproteinase activity (53), and progressive
erosion of the cartilage ending in OA (45,73). Many of
these studies compared their results in ACL transected limbs
with sham-operated limbs, and none found any of the
kinematic changes, cartilage metabolism changes, or any
incidence of OA in the sham-operated limbs (32,53,66,73).
Because these sham operations are designed to create similar
initial inflammatory and healing responses as the ACL
transection operation, the results with sham-operated
animals suggest that mechanical changes in the joint may
be the initiating cause of OA, and that cartilage metabolic
changes are caused by these mechanical changes. This
hypothesis is further supported by the fact that ACL-
transected animals develop OA just as ACL-injured humans
FIGURE 2VFemoral cartilage thickness increases with load for
healthy cartilage. The medial to lateral ratio of the average thickness
of the weight-bearing areas was positively correlated to the peak knee
adduction moment, normalized as a percentage of body weight time
height (%Bw * ht). Modified from Andriacchi et al. (6), with
permission.
http://www.acsm-msse.org
do, even though a surgical transection does not create the
concomitant trauma to the knee joint often seen in ACL
injury cases, such as bone contusions or meniscal tears.
The kinematic changes noted above are important to
consider in the context of how cartilage adapts to its local
load history.
CARTILAGE RESPONDS TO APPLIED LOADS
Cartilage has been reported to be particularly adapted to
the chronic loading that occurs during walking. For
example, the knee adduction moment during walking is
commonly used as an estimate of the load distribution
between the medial and lateral compartment (57). Thus, the
higher the adduction moment, the greater the load on the
medial plateau relative to the load on the lateral plateau.
Healthy subjects were found to have a positive relationship
between the knee adduction moment and the relative
thickness of the medial femoral cartilage (Fig. 2) (6).
Subjects with a higher proportion of the compressive
load borne by the medial compartment had relatively
thicker medial femoral cartilage, using each individual
subject_s lateral femoral cartilage as a matched control.
Using MRI of both femoral and tibial cartilage, several
studies have also observed that the thickest areas of the
cartilage occur where the tibia and femur contact at full
extension (Fig. 3) (39,43), which is also the contact point at
heel strike during walking. Because large compressive
forces during walking occur at heel strike (57), these thick
regions most likely develop as a positive response to
loading.
In vivo studies of immobilized populations have also
shown a positive relationship between loading and cartilage
thickness in the healthy joint using quantitative magnetic
resonance imaging. Studies on patients who have suffered
paralysis after traumatic spinal cord injury have shown that
the lack of loading from muscle activity or external loading
FIGURE 3VLeft, Superior views of thickness maps of the healthy
articular cartilage of the femur and tibia, derived from MRI. Right,
The thickest regions of the femoral cartilage (outlined) align with the
thickest regions of the tibial cartilage at full extension. Modified from
Andriacchi et al. (6), with permission.
INITIATION OF OSTEOARTHRITIS AFTER ACL INJURY
Copyright @ 2008 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
results in cartilage thinning at the knee and shoulder
(63,64). These results provide further evidence that the
mechanical loading being removed because of immobiliza-
CLINICAL SCIENCES
tion is a critical factor in cartilage thinning, rather than any
systemic physiological changes caused by the whole body
being immobilized.
The in vivo response of cartilage to functional loads
described above is consistent with laboratory studies that
observed that cartilage adjusts its metabolism in response to
applied loads. In the laboratory, cartilage response to load
has been shown at scales ranging from the cellular to tissue
to the whole joint. At the cellular scale, both hydrostatic
compression and shear have been applied to two-dimensional
monolayer chondrocyte cultures (18,20,21,25,34,58,59) and
to three-dimensional agarose gels seeded with chondrocytes
(15,24,38,41). In response to dynamic hydrostatic compres-
sion, chondrocytes proliferate (41) and create more extrac-
ellular matrix components such as proteoglycans (24,25,38)
and type II collagen (34). Applied shear stresses also trigger
changes in chondrocyte metabolism, including increases in
proteoglycan production and the reduced expression of
matrix metalloproteinases (18,58,59). Chondrocytes also
respond to loading by changing their volume and aspect
ratio (28,58).
Cartilage in tissue explants demonstrates very similar
behavior, including increased proteoglycan deposition in
response to compression (14,54,72). In addition, alterations
to the cytoskeleton have been observed that vary with the
magnitude of the applied compression (22). It should be
noted that this response is not consistent across the cartilage
or across different magnitudes/durations of loading; the
creation and destruction of matrix components throughout
the cartilage seem to be governed by changes in fluid flow
(14), magnitudes of tissue stresses (72), and proximity to
the chondrocytes (54). The effects of these metabolic
responses that occur at the cellular and tissue levels can
also be observed in laboratory studies examining the whole
joint in vivo. In rabbits, elimination of loading through
immobilization of the hind limb has been shown to result in
OA (65). During a shorter duration of immobilization,
cartilage thinning can be observed in the dog model (10,36).
Moreover, loose immobilization allowing some cyclic
loading of the joint results in less irreversible proteoglycan
loss than rigid fixation (10). As expected, increased loading
on the limb results in thicker cartilage and elevated
proteoglycan content, whether the increased loading comes
because of immobilization of the opposite limb (36) or
because of increased exercise (37).
Histologically, the collagen structure and chondrocyte
morphology both seem to develop topographical variations
based on the local loading environments they experience.
Given the known influence of mechanical loads on the
organization of other connective tissues (e.g., ligament,
bone, vascular tissues), it is likely that mechanics plays an
important role in cartilage organization. The cartilage in the
central regions of the tibial plateau (i.e., where it directly
Medicine & Science in Sports & Exercised 217
CLINICAL SCIENCES

FIGURE 4VScanning electron and confocal micrographs of the topographical variations in collagen orientation and chondrocyte morphology in
porcine tibial cartilage in high-weight-bearing regions (left) and low-weight-bearing regions under the meniscus (right). In the high-weight-bearing
region, the collagen orientation is less ordered and chondrocytes are larger and rounder in the superficial layer. In the low-weight-bearing region, the
collagen orientation is more ordered and tangential and the chondrocytes are smaller and more oblong in the superficial layer. Collagen orientation
is shown in freeze-fractured specimens examined with scanning electron microscopy (middle row). Relative chondrocyte morphology is shown in
explants examined using confocal microscopy (bottom row).

contacts the femoral cartilage) shows a less-organized
superficial zone with more random collagen fiber orienta-
tion (7,13,16) and larger, rounder chondrocytes (13,44,55)
(Fig. 4, left). In contrast, the cartilage in the peripheral
regions of the tibial plateau (i.e., under the meniscus) shows
a more organized, well-defined superficial zone of collagen
fibers (7,13,16,23) and smaller, flatter chondrocytes
(13,23,44,55) oriented more tangential to the surface
(Fig. 4, right). Given the role of collagen in supporting
tensile loads in cartilage, the more organized matrix near the
periphery may be attributable to the higher tensile loads
tangential to the surface in that region. Indeed, computa-
tional models to predict cartilage growth that assume that
the collagen fibers align with maximum local tensile load
show good agreement to experimentally observed collagen
organization (69). These results provide further evidence
that the cartilage reacts and adapts to the loading environ-
ment it experiences on the level of individual chondrocytes,
both across the surface as well as through its depth. In
addition, the topographical variations in cartilage structure
support a mechanism for the initial breakdown of the
cartilage after a shift in joint motion and loading, because
the different collagen structures and chondrocyte morphol-
ogies seem to be both conditioned to their load history and
likely have very different abilities to withstand compres-
sive, tensile, or shear loads.
The laboratory studies described above suggest a poten-
tial process for the initiation of OA at the knee after ACL
injury, involving dramatic changes in the joint_s loading,
structural properties, and/or biology. These changes lead to
initial degeneration of the cartilage, which may then push
the cartilage into a phase of progression characterized by a
positive feedback loop, where increased loads lead to
increased degeneration, which then leads to structural
changes in the joint such as medial joint space narrowing
that increase the loads even further (6). The ACL-injured
knee presents a valuable model for understanding the
initiation of OA more deeply, because ACL injury causes

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Copyright @ 2008 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
changes in the motion of the joint and may also cause long- that happen to the knee joint after ACL rupture, point to a
term alterations in biological activity. mechanism of initiation of OA (Fig. 5). As demonstrated
above with many studies using different measurement

A MECHANISM FOR THE INITIATION OF OA
AFTER ACL INJURY
The evidence presented above for the response of cartilage
to loading, as well as the kinematic and degenerative changes
CLINICAL SCIENCES
modalities, ACL injury causes knee motion to change
substantially, resulting in a shift in which regions of the
cartilage are in contact. This shift likely causes increased
loading in areas not conditioned to frequent load bearing, as
well as reduced loading in areas conditioned to frequent

FIGURE 5VA proposed mechanism of initiation of osteoarthritis after ACL injury. Healthy cartilage that has developed heterogeneous specialized
structural morphology over a lifetime is subjected to abnormal motion and loading after ACL injury. These rapid changes result in fibrillation and
other structural breakdown as well as catabolic biological responses, initiating the pathway to osteoarthritis.

INITIATION OF OSTEOARTHRITIS AFTER ACL INJURY Medicine & Science in Sports & Exercised 219

Copyright @ 2008 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
 load bearing. Such shifts alter the contact pressure distribu-
tions under static loading (1). An internal tibial rotation of
10- did not seem to cause a large change in the loading on
CLINICAL SCIENCES
medial side, but it did result in a posterior shift in the
contact pressure on the lateral side.
Spatial variations in cartilage morphology and mechanical
properties are clearly related to regions of functional load
bearing (7,12,13,16,69,71). The central regions, which likely
undergo the highest compressive loads tangential to the
surface because of lateral expansion of the fluid when the
tissue is loaded (1,51), show increased thickness and a less
organized superficial layer of collagen fibers. In contrast, the
peripheral regions, which likely receive more tensile tangential
loading, are thinner but show a more well-defined superficial
layer with more tangential collagen fiber orientation (7,13,16).
It currently remains unknown what the implications for these
differences in collagen fiber orientation and chondrocyte
morphology may be on the ability of cartilage to withstand
different types of load. It has been observed that the peripheral
regions of the cartilage have a higher tensile stiffness than the
central regions (2), which may suggest that the more well-
defined superficial layer is better able to withstand tensile or
shear loading, whereas the less-organized superficial layer may
be more susceptible to fibrillation. If the peripheral region of
cartilage with a more well-defined superficial layer is also less
permeable to water (52,62), it may also be able to better
maintain fluid pressure, allowing the water in the central
regions of the cartilage to support the compressive load (52).
In contrast, the thicker, less-organized central regions of the
cartilage may be more capable of withstanding compressive
load without structural breakdown of the matrix occurring
(70). By this explanation, a shift in the load-bearing area as
occurs in the ACL-deficient knee to an infrequently loaded
area may cause articular surface damage and increase
fibrillation of the collagen network, especially if this shift
occurs rapidly and does not allow for adaptation. On the other
hand, removing direct femoral loads from the previously load-
bearing area, so that this area is now at the edge of the loaded
regions, may cause a dramatic change in the tangential loads
on that area, which may also lead to surface damage or
increased fibrillation. It remains unclear whether simple
compressive overloading or altered loading from compression
to tension or vice versa predominates during initiation of OA,
and more research is necessary to determine the relative
importance of the two possible phenomena. However, the
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mechanism for the premature initiation of OA after ACL
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