Non-traumatic anterior cruciate ligament abnormalities and their relationship to osteoarthritis using morphological grading and cartilage T2 relaxation times: data from the Osteoarthritis Initiative (OAI).
ABSTRACT The aim of this work was to study anterior cruciate ligament (ACL) degeneration in relation to MRI-based morphological knee abnormalities and cartilage T(2) relaxation times in subjects with symptomatic osteoarthritis.
Two radiologists screened the right knee MRI of 304 randomly selected participants in the Osteoarthritis Initiative cohort with symptomatic OA, for ACL abnormalities. Of the 52 knees with abnormalities, 28 had mucoid degeneration, 12 had partially torn ACLs, and 12 had completely torn ACLs. Fifty-three randomly selected subjects with normal ACLs served as controls. Morphological knee abnormalities were graded using the WORMS score. Cartilage was segmented and compartment-specific T(2) values were calculated.
Compared to normal ACL knees, those with ACL abnormalities had a greater prevalence of, and more severe, cartilage, meniscal, bone marrow, subchondral cyst, and medial collateral ligament lesions (all p < 0.05). T(2) measurements did not significantly differ by ACL status.
ACL abnormalities were associated with more severe degenerative changes, likely because of greater joint instability. T2 measurements may not be well suited to assess advanced cartilage degeneration.
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ABSTRACT: Objective. To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissues and ligament cells from normal and osteoarthritis-affected knees. Methods. Knee joints were obtained at autopsy within 24-48 hours postmortem from 13 normal donors (age 36.9±11.0 years), 16 OA donors (age 79.7±11.4 years) and 8 old donors without OA (age 76.9±12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative PCR. ACL-derived cells were used to study regulation of MKX expression by IL-1β. MKX was knocked down by siRNA to analyze function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. Results. The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry showed that MKX positive cells were significantly reduced in ACL tissues from OA donors in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1β strongly suppressed MKX gene expression and reduced ligament ECM genes, COL1A1 and TNXB. On the other hand, SOX9, chondrocyte master transcription factor, was up regulated by IL-1β treatment. Importantly, knock down of MKX expression by siRNA upregulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB were decreased. Conclusion. Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints and this may be in part mediated by IL-1β. MKX appears necessary to maintain the tissue specific cellular differentiation status and ECM production in adult human tendons and ligaments. © 2013 American College of Rheumatology.Arthritis & Rheumatology 05/2013; · 7.48 Impact Factor
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ABSTRACT: To review recent original research publications related to imaging of osteoarthritis and identify emerging trends and significant advances. Relevant articles were identified through a search of the PubMed database using the query terms "osteoarthritis" in combination with "imaging", "radiography", "MRI", "ultrasound", "computed tomography",and "nuclear medicine"; either published or in press between March 2012 and March 2013. Abstracts were reviewed to exclude review articles, case reports, and studies not focused on imaging using routine clinical imaging measures. Initial query yielded 932 references, which were reduced to 328 citations following the initial review. MRI (118 references) and radiography (129 refs) remain the primary imaging modalities in OA studies, with fewer reports using CT (35 refs) and ultrasound (23 refs). MRI parametric mapping techniques remain an active research area (33 refs) with growth in T2*- and T1rho mapping publications compared to prior years. Although the knee is the major joint studied (210 refs) there is interest in the hip (106 refs) and hand (29 refs). Imaging continues to focus on evaluation of cartilage (173 refs) and bone (119 refs). Imaging plays a major role in osteoarthritis research with publications continuing along traditional lines of investigation. Translational and clinical research application of compositional MRI techniques is becoming more common driven in part by the availability of T2 mapping data from the OAI. New imaging techniques continue to be developed with a goal of identifying methods with greater specificity and responsiveness to changes in the joint, and novel functional neuroimaging techniques to study central pain. Publications related to imaging of OA continue to be heavily focused on quantitative and semiquantitative MRI evaluation of the knee with increasing applicationof compositional MRI techniques in the hip.Osteoarthritis and Cartilage 07/2013; · 4.26 Impact Factor
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ABSTRACT: The aim of this study was to examine serum non-coding RNAs as potential biomarkers for cartilage damage associated with anterior cruciate ligament (ACL) injury. Serum was obtained from 80 patients 1 year after surgery for ACL injury and 60 normal donors without overt skeletal injury. Total serum RNA was isolated, small non-coding RNAs profiled by TaqMan array MicroRNA (miRNA) analysis and individual small RNA assays performed by quantitative TaqMan RT-PCR (qPCR). Semi-quantitative magnetic resonance imaging (MRI) analysis was performed using Whole Organ Magnetic Resonance Knee Score (WORMS) scoring for analysis of cartilage damage. Initial TaqMan array miRNA profiling showed an increased serum concentration of a small nucleolar RNA (snoRNA), U48, in five patients with cartilage damage compared with that in five patients without cartilage damage and six normal donors. Independent qPCR analysis of snoRNAs in serum from all patients and normal donors showed a strong association between the serum level of another snoRNA, U38, and cartilage damage in ACL injury patients and together with snoRNA, U48, clear distinction between ACL injury patients and normal donors. SnoRNAs U38 and U48 are significantly elevated in the serum of patients developing cartilage damage at 1 year after ACL injury. Serum levels of U38 have the potential to facilitate early diagnosis of patients with cartilage damage after ACL injury. This study suggests serum non-coding RNAs may serve as novel noninvasive biomarkers for the detection and assessment of cartilage damage after ACL injury.Osteoarthritis and Cartilage 08/2012; 20(12):1631-7. · 4.26 Impact Factor
Non-traumatic anterior cruciate ligament abnormalities
and their relationship to osteoarthritis using morphological
grading and cartilage T2 relaxation times: data
from the Osteoarthritis Initiative (OAI)
Keegan K. Hovis & Hamza Alizai & Seng-Choe Tham &
Richard B. Souza & Michael C. Nevitt &
Charles E. McCulloch & Thomas M. Link
Received: 29 December 2011 /Revised: 6 February 2012 /Accepted: 7 February 2012 /Published online: 25 February 2012
Objectives The aim of this work was to study anterior
cruciate ligament (ACL) degeneration in relation to MRI-
based morphological knee abnormalities and cartilage T2
relaxation times in subjects with symptomatic osteoarthritis.
Methods Two radiologists screened the right knee MRI of
304 randomly selected participants in the Osteoarthritis
Initiative cohort with symptomatic OA, for ACL abnormal-
ities. Of the 52 knees with abnormalities, 28 had mucoid
degeneration, 12 had partially torn ACLs, and 12 had com-
pletely torn ACLs. Fifty-three randomly selected subjects
with normal ACLs served as controls. Morphological knee
abnormalities were graded using the WORMS score.
Cartilage was segmented and compartment-specific T2val-
ues were calculated.
Results Compared to normal ACL knees, those with ACL
abnormalities had a greater prevalence of, and more severe,
cartilage, meniscal, bone marrow, subchondral cyst, and
medial collateral ligament lesions (all p<0.05). T2measure-
ments did not significantly differ by ACL status.
Conclusions ACL abnormalities were associated with more
severe degenerative changes, likely because of greater joint
instability. T2 measurements may not be well suited to
assess advanced cartilage degeneration.
Osteoarthritis (OA) is a leading cause of disability worldwide,
with nearly 27 million individuals having clinically symptom-
atic OA and the knee being the most commonly affected joint.
over the age of 65 years [1, 2]. Several factors contribute to the
development and acceleration of OA, such as prior trauma,
knee malalignment, genetics, and obesity, among others [3–5].
The anterior cruciate ligament (ACL) is an important knee
joint stabilizer. A ruptured ACL leads to significant knee
instability, as the ACL is the primary restraint to anterior tibial
translation and internal tibial rotation . Pathologies of the
ACL include those induced by (1) prior trauma, which can
lead to partial or complete ACL tears, and (2) degeneration,
Keegan K. Hovis and Hamza Alizai contributed equally to this study
and should be designated joint first-coauthors.
K. K. Hovis:H. Alizai:S.-C. Tham:R. B. Souza:T. M. Link
Musculoskeletal and Quantitative Imaging Research Group,
Department of Radiology and Biomedical Imaging,
University of California San Francisco,
185 Berry Street, Suite 350,
San Francisco, CA 94107, USA
H. Alizai (*)
Department of Radiology and Biomedical Imaging,
University of California, San Francisco,
185 Berry Street, Suite 350,
San Francisco, CA 94107, USA
M. C. Nevitt:C. E. McCulloch
Department of Epidemiology and Biostatistics,
University of California San Francisco,
185 Berry Street, Suite 350,
San Francisco, CA 94107, USA
Skeletal Radiol (2012) 41:1435–1443
or myxoid material , is considered a less common patholo-
gy. Its etiology has been the subject of much debate with
possible causes ranging from senescence (entrapment of syno-
vial tissue ) to chronic trauma . Although ACL ruptures
resulting from traumatic injuries are associated with premature
knee OA [10–12], there is a paucity of data regarding the
prevalence of degenerative ACL abnormalities among those
with symptomatic OA and whether such abnormalities are
associated with the severity of knee OA.
As magnetic resonance imaging (MRI) is the best imaging
technique to non-invasively visualize articular cartilage, it is an
important tool used to monitor degenerative joint disease.
Furthermore, with the advent of high-field MRI, the detection
and visualization of subtle cartilage lesions have dramatically
improved [13, 14]. Various reliable and reproducible semi-
quantitative measures have been developed to evaluate the
morphological abnormalities associated with knee OA, such
as the Whole-Organ MRI Score (WORMS)  and the
Boston-Leeds OA Knees Score (BLOKS) . MRI also
provides a method to non-invasively detect and quantify the
cartilage biochemical composition using T2and T1rhorelaxa-
tion times. As they provide information on the cartilage colla-
gen content and architecture, water content, and concentration
of glycosaminoglycans, these techniques show promise in the
detection of early cartilage degeneration [17–19].
The purpose of ourstudywas toevaluate the cross-sectional
association of ACL abnormalities with knee morphological
degeneration (based on WORMS scores) and cartilage T2
measurements using knee MRIs of osteoarthritic individuals
from the OA Initiative (OAI). We hypothesized that morpho-
logical cartilage and ligament abnormalities, meniscal lesions,
bone marrow lesions, and subchondral cysts would be more
relaxation times would be higher in these subjects compared to
osteoarthritic controls without ACL abnormalities.
Materials and methods
The data used to prepare this article was obtained from the
Osteoarthritis Initiative (OAI) database, which is available
for public access at http://www.oai.ucsf.edu/. The OAI is an
ongoing multi-center, longitudinal, prospective observation-
al cohort study, focusing primarily on knee OA. The study
protocol, amendments, and informed consent documenta-
tion were reviewed and approved by the local institutional
review boards. Baseline clinical and image datasets 0.C.1
and 0.E.1 obtained from the OAI coordinating center were
used in this cross-sectional study. We analyzed a subset of
individuals from the OAI progression cohort, which is
characterized by the presence of symptomatic OA in at least
one knee. Symptomatic knee OA was defined as the com-
bination of (i) pain, aching or stiffness in or around the knee
on most days for at least 1 month during the past 12 months
and (ii) tibiofemoral osteophytes in the same knee with or
without joint space narrowing (equivalent to Kellgren and
Lawrence (KL) grade of ≥2), representing radiographic
tibiofemoral OA. Exclusion criteria for the OAI included
subjects with a prior traumatic injury, previous knee surgery,
rheumatoid arthritis, bilateral severe knee joint space nar-
rowing, and contraindications or inability for MRI.
Two board-certified musculoskeletal fellowship trained
radiologists (7 and 24 years of experience in musculoskeletal
imaging respectively) independently evaluated the right knee
MRIs of 304 randomly selected progression cohort subjects
grading, a consensus reading was performed. Upon assess-
ment, we identified 52 subjects with abnormal ACLs—28
with mucoid degeneration, 12 with a partial tear, and 12 with
Physical activity levels were assessed in all OAI subjects
using the Physical Activity Scale for the Elderly (PASE).
This is a well-established, reliable, and validated question-
naire that has been used to measure physical activity in
individuals of similar age to those investigated in the current
study [20–22]. The following clinical question asked during
the initial screening for the OAI was used to exclude sub-
jects who reported a history of knee injury, which caused
difficulty walking; “Have you ever injured either of your
knees so badly that it was difficult for you to walk for at
least one week?” The responses were recorded as either
“Yes”, “No”, “Don’t know” or “refused”.
Bilateral standing posteroanterior (PA) “fixed flexion” knee
radiographs were obtained using a Plexiglas frame (Syna-
FlexerTM). The knees had 20˚-30˚ of flexion and the feet
had 10˚ of internal rotation. A focus-to-film distance of 72
inches was used. Baseline knee radiographs were evaluated
by two radiologists in consensus and graded using the
Kellgren-Lawrence (KL) grading scale .
MRI examinations were obtained with dedicated 3-T MRI
systems (Trio, Siemens, Erlangen, Germany) using a quadra-
ture transmit-receive knee coil (USA Instruments, Aurora,
Ohio, USA). The following standard morphologic sequences
1436 Skeletal Radiol (2012) 41:1435–1443
and T2-mapping sequences of the right osteoarthritic
knee were analyzed: (i) coronal intermediate-weighted
(IW) 2-D fast spin-echo (FSE) sequence (TR/TE03700/
29 ms, spatial resolution00.365 × 0.456 mm, slice
thickness03.0 mm), (ii) sagittal 3-D dual-echo in steady
state (DESS) sequence with selective water excitation
(WE) with coronal and axial reformations (TR/TE0
16.3/4.7, flip angle025°, spatial resolution00.365 ×
0.456 mm, slice thickness00.7 mm), (iii) sagittal 2-D
IW FSE sequence with fat suppression (FS) (TR/TE0
3,200/30 ms, spatial resolution00.357 × 0.511 mm, slice
thickness03.0 mm) and (iv) sagittal T2-weighted 2-D
multi-echo (ME) spin-echo (SE) sequences (TR0
2,700 ms, TE010, 20, 30, 40, 50, 60, and 70 ms, spatial
resolution00.313 × 0.446 mm, slice thickness03.0 mm,
and 0.5 mm gap), as previously described in detail .
Grading of the ACL
Abnormalities of the ACL included (i) mucoid degeneration,
(ii) partial tear, and (iii) complete tear. Mucoid degeneration
on MRI is characterized by an ill-defined and thickened
ligament with increased signal intensity on all sequences
including DESS and IW FSE, which were available for inter-
is a loss of the normal linear fibrillary pattern on the low TE
images (coronal 2D IW FSE sequence), but a retention of the
FSE fat-saturated sequence . Though in our study the TEs
are not significantly different, the sagittal fat-suppressed FSE
images are still more fluid-sensitive and thus show better
contrast of ACL fibers compared to surrounding high signal
tissue than the non-fat-suppressed weighted FSE images in
mucoid degeneration. A partially torn ACL showed a disrup-
tion of some of its fibers with the remaining ones being
continuous, as previously described . Some authors have
reported that partial tears of the ACL and mucoid degenera-
tion can be difficult to differentiate on MR and require arthro-
scopic correlation . Therefore, these two abnormalities
weregrouped togethertoforma “Non-Complete Tear” group.
Complete tears of either the anteromedial or posterolateral
bundle were also graded as partial. ACLs with partial tears
typically had a thinned cross section asopposed toACLs with
mucoid degeneration. A completely torn ACL was diagnosed
when there was a complete loss of continuous fibers of the
ligament, the ACL was not attaching to the femur with an
abnormal orientation, and a fluid gap was visualized com-
pletely separating the proximal and distal portions in fluid-
sensitive sequences .
Semi-quantitative morphological analyses
MR images of the right knee were analyzed on picture
archiving communication system (PACS) workstations
(Agfa, Ridgefield Park, NJ, USA). Awhole-organ magnetic
resonance imaging score (WORMS)  was used to
Fig. 1 Sagittal IW FS images
of the knee. a Normal
ACL - continuity of its fibers.
b Non-complete ACL
tear - increased signal intensity
and a swollen appearance but
fibrillary continuity of the
ligament is preserved, findings
are consistent with mucoid
degeneration. c Complete
tear - complete disruption
of the ACL
Skeletal Radiol (2012) 41:1435–14431437
evaluate the images for OA-related abnormalities of the
knee, as previously described . The following anatom-
ical compartments were analyzed separately: (i) patella, (ii)
trochlea, (iii) medial femur, (iv) medial tibia, (v) lateral
femur, and (vi) lateral tibia. Using the semi-quantitative
scoring system, the following joint structures were separate-
ly evaluated: (i) cartilage, (ii) menisci, (iii) bone marrow
lesions, (iv) subchondral cysts, and (v) medial collateral
ligament, as previously described in detail . The mean
of cartilage WORMS scores for all subregions in a knee as
well as the percentage of knees with mean cartilage scores
>3, which indicate more diffuse degeneration, were used to
assess cartilage degeneration. WORMS scores summed over
all subregions were used to assess bone marrow lesions,
subchondral cysts, medial meniscus, and lateral meniscus.
Additionally, global joint WORMS scores were calculated
for the medial tibiofemoral joint (MTFJ), lateral tibiofe-
moral joint (LTFJ), patellofemoral joint (PFJ), and total joint
so that the severity of degeneration could be assessed for
each region. This was done by adding together the cartilage,
ligament, subchondral cyst, and bone marrow lesion
WORMS scores for each compartment.
Two board-certified radiologists with 24 and 7 years of
experience in musculoskeletal imaging separately graded
the images. If WORMS scores were not identical, consensus
readings were performed. During the reading session, am-
bient light was reduced. Radiologists had access to all of the
acquired sequences, and no time constraints were used.
T2 relaxation time
The T2relaxation time was approximated by fitting an
exponential function to the signal intensity at different echo
times as follows: SI(TE)~exp(–TE/ T2), where SI(TE) is the
signal intensity as a function of echo time and T2is the
transverse relaxation time. A monoexponential decay model
was used .
Images were transferred to a remote SUN/SPARC work-
station (Sun Microsystems, Mountain View, CA, USA) and
analyzed with software developed at our institution using an
Interactive Display Language (IDL) (Research Systems,
Boulder, CO, USA) environment. Manual segmentation of
the cartilage in the patella, medial femoral condyle (MFC),
medial tibia (MT), lateral femoral condyle (LFC), and lateral
tibia (LT) was performed on the T2maps from the sagittal 2-
D ME SE sequences of the right knee, as previously de-
scribed in detail . Rarely, the cartilage was absent or
significantly thinned, making segmentation not possible;
these individual compartments were not segmented and
accounted for as missing data during the statistical analysis.
The whole compartment of each region was segmented on
all slices with well-visualized artifact-free cartilage. The
trochlea was not segmented because of the interfering flow
artifacts from the popliteal artery. An IDL routine was used
to simplify the manual drawing of splines delineating carti-
lage areas. The mean T2values from the regions of interest
created in the T2maps were subsequently calculated.
Thirteen subjects were randomly selected out of the 105
subjects (with and without ACL abnormalities) enrolled in
the study. Grading of the ACL was performed in these 13
subjects twice by two radiologists and reproducibility was
determined with Cohen’s kappa values. There was an inter-
val of 4 weeks between the two reproducibility readings.
Reproducibility for the semi-quantitative WORMS score
was demonstrated to be good in a prior study, with the
Cohen’s kappa values equal to 0.76 and 0.72 for the inter-
observer and intra-observer agreement, respectively .
Reproducibility of the quantitative T2measurements was
evaluated with two repeated segmentations done for each
of ten randomly selected subjects with an interval of 3 weeks
between the two segmentations. Inter-observer and intra-
observer agreement was determined using global intraclass
Statistical analysis was performed with JMP software, version
7 (SAS Institute, Cary, NC). Multiple linear and logistic
regression models were used to determine significant differ-
ences in WORMS scores and T2values between knees with a
normal and abnormal ACL. The knees in the “non-complete
tear” group and those with complete tears were compared to
each other and they were assessed together as one group and
separately against the normal ACL subjects. All WORMS
analyseswere adjustedfor age,sex,andBMI,andT2analyses
werealsoadjustedfor KLgrades. WORMSanalyseswerenot
controlled for KL grades because we expect WORMS scores
to increase as KL grades increase. Statistical significance was
defined for all calculations as p < 0.05.
Of the 304 subjects with symptomatic knee OA, 52 (17.1%)
hadabnormalACLs,28 (9.2%)withmucoiddegeneration, 12
(3.9%) with a partial tear, and 12 (3.9%) with a complete tear.
As outlined previously, differentiation between mucoid de-
generation and partial tear is limited. We therefore combined
the partial tear and mucoid degeneration groups and defined
them as non-complete tear group (n040, 13.1%). Subject
characteristics are displayed in Table 1. The WORMS scores
1438Skeletal Radiol (2012) 41:1435–1443
of males and females did not significantly differ in either the
normal or abnormal ACL groups; thus, they were evaluated
togetherin all analyses. Higher KL grades (KL>2)were more
frequent in the abnormal ACL group.
ACL abnormalities in relation to WORMS
When evaluating cartilage lesions (Table 2), the abnormal
ACL knees had significantly higher mean cartilage
WORMS scores than the normal ACL group in all compart-
ments (p≤0.05) except the patella, which was trending
toward significance. The individual ACL abnormalities
(non-complete tear and complete tear groups) also displayed
significantly higher WORMS scores in all compartments of
the knee except for the patella in the complete tear group,
when compared to the normal ACL group (p<0.05). Similar
results were found when evaluating the percentage of sub-
jects with more advanced cartilage degenerative disease
(WORMS scores >3, Table 2).
When evaluating the other joint structures except the
MCL, the abnormal ACL group displayed significantly
greater WORMS scores than the normal group in all struc-
tures (Table 2). Compared to the normal ACL group,
WORMS scores were significantly higher in the medial
meniscus of the complete tear group (p≤0.0001) and the
non-complete tear group (p00.0059). The non-complete
tear group also had significantly higher WORMS scores
than the normal knees for all other structures of the joint
(p<0.05). The complete tear ACL group had significantly
higher WORMS scores for subchondral cysts and bone
marrow lesions, than the control group (p≤0.05), but no
difference in other structures, which may have been related
in part to the smaller number of subjects in this group.
When global joint WORMS scores were assessed, the
abnormal ACL group displayed significantly higher
WORMS scores than the normal ACL group in all regions,
but to a greater degree in the MTFJ and total joint (Table 2).
Comparing the individual ACL pathologies to the control
group, they had significantly higher WORMS scores in all
regions (p<0.05), except for the LTFJ and the PFJ of com-
pletely torn ACL subjects.
Differences between the individual ACL abnormality
Comparing the WORMS scores of the non-complete and
complete tear group revealed few differences (Table 2).
However, it should be noted that the completely torn ACL
group had significantly higher medial meniscal WORMS
scores than the non-complete tear group (p00.035).
Cartilage T2relaxation times in relation to ACL
T2values of abnormal ACL subjects were trending toward
being lower than normal ACL subjects in the MFC (p0
0.091) and MT (p00.078), but no significant differences
were found (Table 3). When assessing the individual ACL
pathologies, the only significant relationship was that the
completely torn ACL group had lower T2values than the
control group in the MT (36.9 ms vs. 38.1, p00.022).
The reproducibility for grading of the ACL into the different
categories was excellent with the Cohen’s kappa values
equal to 0.850 and 0.925 for the inter-observer and intra-
observer agreements, respectively. Using the global intra-
class correlation coefficient, the T2measurement inter-
observer and intra-observer agreements were found to be
0.990 and 0.994, respectively.
The results of our study suggest that ACL abnormalities are
fairly prevalent in subjects with symptomatic knee OA
(17%) who do not have a self-reported history of a knee
Table 1 Subject characteristicsa
aValues are expressed as mean ±
SD unless otherwise noted
*Significantly different if
Normal ACL (n053) Abnormal ACL (n052)p value t test
Anterior tibial translation (cm)
KL Grade 1
KL Grade 2
KL Grade 3
KL Grade 4
11 males, 42 females
23 males, 29 females
Skeletal Radiol (2012) 41:1435–14431439
Table 2 Comparison of normal and abnormal ACL knees using WORMS. Comparison of individual ACL abnormalities using WORMSa,d
WORMS Abnormal vs. normal ACLDifferences in individual ACL abnormalities
p value (normal vs.
Bone marrow lesionse
MCL tear presentc
aValues are the mean ± SD unless otherwise noted; all analyses adjusted for age, sex, and BMI
bMean cartilage WORMS >3 expressed in number of subjects (%)
cNumber of subjects (%)
dLogistic regression analysis unless otherwise noted
eMultiple linear regression analysis
*WORMS of abnormal ACL group > normal ACL group (p<0.05)
^WORMS of complete tear > non-complete tear group (p00.035)
MFC medial femoral condyle, MT medial tibia, LFC lateral femoral condyle, LT lateral tibia, MCL medial collateral ligament
MTFJ medial tibiofemoral joint, LTFJ lateral tibiofemoral joint, PFJ patellofemoral joint
Table 3 Cartilage T2 values of normal ACL knees compared to abnormal ACL knees in all five compartments
T2 valuesNormal ACL (n053) Abnormal ACL (n052)p value
Medial femoral condyle
Lateral femoral condyle
aValues are the mean ± SD. T2 values are in ms
bMultiple linear regression analysis adjusted for age, sex, BMI, and KL grades
*Signficantly different (p<0.05)
1440Skeletal Radiol (2012) 41:1435–1443
injury that caused difficulty walking. We found significantly
more severe degenerative changes in subjects with abnormal
ACLs compared to normal ACL subjects, as evidenced by
higher WORMS scores in all joint structures (cartilage,
menisci, bone marrow lesions, subchondral cysts, and
MCL) and in all compartments of the knee, though partic-
ularly in the medial compartment. Surprisingly, the severity
of degeneration in the knee joint did not differ between the
complete and non-complete ACL groups, except in the
medial meniscus. Contrary to our hypothesis, cartilage T2
relaxation times were not associated with ACL abnormali-
ties; this may be due to the severe cartilage degeneration in
our subjects with established OA, as it substantially limits
segmentation and T2analysis.
We found that 17.1% of knees in our study with mostly
mild and moderate OA (94% of knees with ACL abnormal-
ities had a KL grade of 2 or 3 at baseline) had abnormalities
of their ACLs, a finding that has been reported to be as high
as 64% in knees with more advanced OA . Although
mucoid degeneration has been regarded as a rare pathology
, we found its presence in 9.2% of our subjects. Al-
though ACL tears  and mucoid degeneration  have
been described in osteoarthritic knees, the exact cause of
such ACL changes is not completely understood, particular-
ly because many (and all of the subjects in the present study)
do not recall a prior knee injury. It has been suggested that
intercondylar notch stenosis caused by osteophytes produ-
ces a shear force during flexion and extension, which even-
tually damages the ACL . Cushner and colleagues
harvested 19 ACLs from patients undergoing total knee
arthroplasty and found loose, fibrous tissue and myxoid
and cystic occurrences to be common forms of degeneration
. Additionally, McIntyre  observed that one out of
ten of his subjects with mucoid degeneration developed a
non-traumatic ACL tear within a year. This perhaps lends
credence that these ACL changes are part of a continuum of
senescence and degeneration.
Our data suggests that in individuals with symptomatic
OA, ACL abnormalities are associated with more severe
knee degeneration, based on WORMS scores. It has been
speculated that the antero-posterior and rotatory instability
of ACL-deficient knees increases the shear force to the
cartilage, contributing to accelerated OA . Additionally,
external adduction moments are elevated in ACL-deficient
knees, increasing medial loads and thus the risk for medial
degeneration [34, 35]. In fact, we found that the cartilage
WORMS scores did not differ significantly between the
types of ACL pathology. Compared to the osteoarthritic
subjects with normal ACLs, the subjects in the two abnor-
mal ACL groups had greater cartilage degeneration (based
on mean WORMS scores and percentage of subjects with
WORMS scores greater than 3) in all compartments except
the patella, though the medial compartments displayed the
greatest significance. The patellar WORMS scores did not
significantly differ from the controls likely because the
controls had relatively severe patellar degeneration.
Our data is in agreement with two previous studies [7,
36] that evaluated subjects with symptomatic OA and com-
plete ACL tears. Amin and colleagues  found through a
30-month longitudinal study that ACL-deficient knees had
accelerated cartilage degeneration, based on WORMS, in
the medial tibiofemoral joint and there was a trend in the
lateral tibiofemoral joint, but no association was found in
the patellofemoral joint. Furthermore, Hill et al.  found
ACL-deficient knees to have more severe medial radio-
graphic OA. Roughly half of the subjects in each of these
studies recalled a previous knee injury; we excluded these
subjects because prior injury is a known risk factor for OA.
Additionally, we evaluated individuals with mucoid degen-
eration and partial tears rather than only those with complete
The medial meniscus was the only structure that differed
between the two ACL pathologies. The completely torn
ACL group had greater medial meniscal degeneration than
the other group. Despite the marginal p value for this dif-
ference, it is supported by prior research. It is well docu-
mented that chronically ACL-deficient knees have increased
incidence of medial meniscal tears [36–38]. It is postulated
that the posterior horn acts as a buttress by wedging against
the posterior aspect of the MFC to prevent posterior femoral
translation (and concurrent anterior tibial translation). In an
ACL-deficient knee, the demand on the medial meniscus to
resist anterior tibial translation significantly increases,
which could explain the increased incidence of meniscal
Despite the known predisposition for medial compart-
ment degeneration, an association was also seen within the
rest of the joint in those with an abnormal ACL, as
evidenced by the global WORMS scores. This global joint
degeneration is likely the result of intermediate to long-term
sequelae of the degenerated ACL.
Cartilage T2values have been utilized to detect the early
biochemical changes that precede morphological deteriora-
tion . These changes are primarily related to the carti-
lage water content, macromolecular composition, and
organization of the collagen fibers . The only significant
difference we found in T2values was that the completely
torn ACL group had lower MT T2values than the normal
ACL group, which was not expected as more degenerated
cartilage should have higher T2measurements. However, T2
measurements may be better suited to detect early OA rather
than assess advanced OA; David-Vaudey et al.  showed
an increase followed by a decrease in cartilage T2relaxation
times with a histological grading of 1 and 2 (simplified
Mankin’s criteria), respectively. This was postulated to be
related to the anisotropy of collagen fibrils, causing an
Skeletal Radiol (2012) 41:1435–1443 1441
increase in T2values in grade 1 histological changes before
sufficient loss of water content results in decreased T2
values in grade 2 histological changes. It is possible that
the cartilage of our subjects was beginning to undergo grade
2 histological changes.
A limitation of the study is that arthroscopic correlation
with the MR diagnosed ACL abnormalities was not possi-
ble. Another limitation is the evaluation of ACL without
longer TE T2 images, which can make it difficult to differ-
entiate between the types of ACL abnormalities. The diag-
nostic accuracy of 3-T MRI for ACL abnormalities varies in
literature; Dyke et. al found an accuracy of 97% for com-
plete ACL tears and 95% for partial tears upon correlation
with arthroscopy . We acknowledge the difficulty in
segmenting the cartilage of subjects with established OA,
as only visible remnant cartilage is targeted. Areas of de-
nuded full-thickness cartilage loss, contributing to a
WORMS grade of 5 or 6, have no segmentable cartilage.
Changes in cartilage of severe OA knees would hence not be
fully represented by the T2values and require quantification
using the WORMS morphological score. This further sug-
gests that T2quantification is better suited to detect early
OA prior to morphological deterioration.
Another limitation was a relatively small sample of sub-
jects ACL abnormalities. This may have affected our ability
to detect significant differences in these groups. Future
studies with a larger number of subjects and a longitudinal
follow-up are needed to elucidate the relationship between
ACL abnormality and progression of OA. A longitudinal
follow-up may also determine the impact of worsening OA
on the ACL.
In summary, when evaluating symptomatic osteoarthritic
subjects, we found that an abnormal degenerated ACL was
associated with more severe pathology of knee OA in mul-
tiple joint structures assessed by MRI, particularly in the
medial compartment. The severity of degeneration between
the two abnormal ACL groups (the non-complete tear and
complete tear groups) did not differ in any structure except
for the medial meniscus, which was more degenerated in the
completely torn ACL group. Cartilage T2relaxation times
did not show significant differences between normal and
abnormal ACL groups with established OA, suggesting that
cartilage T2values may be less suited to assess more ad-
vanced cartilage degeneration.
prised of five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-
2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National
Institutes of Health, a branch of the Department of Health and Human
Services, and conducted by the OAI Study Investigators. This study
The OAI is a public-private partnership com-
was also funded in part by the Intramural Research Program of the
National Institute on Aging. Private funding partners include Pfizer,
Inc.; Novartis Pharmaceuticals Corporation; Merck Research Labora-
tories; and GlaxoSmithKline. Private sector funding for the OAI is
managed by the Foundation for the National Institutes of Health. In
addition, the analyses performed in this study were funded through the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIH U01AR059507-01. This manuscript has received the approval of
the OAI Publications Committee based on a review of its scientific
content and data interpretation.
The authors would like to thank our colleagues John A. Lynch,
PhD, and Bryan Haughom for their contributions during the early
stages of the study.
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