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Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study

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Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study

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Given the emerging evidence that osteoarthritis (OA) may have a vascular basis, the aim of this study was to determine whether serum lipids were associated with change in knee cartilage, presence of bone marrow lesions (BMLs) at baseline and the development of new BMLs over a 2-year period in a population of pain-free women in mid-life. One hundred forty-eight women 40 to 67 years old underwent magnetic resonance imaging (MRI) of their dominant knee at baseline and 2.2 (standard deviation 0.12) years later. Cartilage volume and BMLs were determined for both time points. Serum lipids were measured from a single-morning fasting blood test approximately 1.5 years prior to the MRI. The incidence of BML at follow-up was associated with higher levels of total cholesterol (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.01, 3.36; P = 0.048) and triglycerides (OR 8.4, 95% CI 1.63, 43.43; P = 0.01), but not high-density lipoprotein (HDL) (P = 0.93), low-density lipoprotein (LDL) (P = 0.20) or total cholesterol/HDL ratio (P = 0.17). No association between total cholesterol, triglycerides, HDL, LDL or total cholesterol/HDL ratio and presence of BMLs at baseline or annual change in total tibial cartilage volume was observed. In this study of asymptomatic middle-aged women with no clinical knee OA, serum cholesterol and triglyceride levels were associated with the incidence of BMLs over 2 years. This provides support for the hypothesis that vascular pathology may have a role in the pathogenesis of knee OA. Further work is warranted to clarify this and whether treatments aimed at reducing serum lipids may have a role in reducing the burden of knee OA.
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Vol 11 No 6
Research article
Total cholesterol and triglycerides are associated with the
development of new bone marrow lesions in asymptomatic
middle-aged women - a prospective cohort study
Miranda L Davies-Tuck1, Fahad Hanna1,2,3, Susan R Davis3, Robin J Bell1, Sonia L Davison3,
Anita E Wluka1,2, Jenny Adams3 and Flavia M Cicuttini1
1Department of Epidemiology and Preventive Medicine, Monash University Medical School, Alfred Hospital, 89 Commercial Road, Prahran, Victoria
3004, Australia
2Baker Heart Research Institute, Commercial Road, Melbourne, Victoria 3004, Australia
3The Women's Health Program, Department of Medicine, Monash University Medical School, Alfred Hospital, 89 Commercial Road, Prahran, Victoria
3181, Australia
Corresponding author: Flavia M Cicuttini, Flavia.cicuttini@med.monash.edu.au
Received: 14 Apr 2009 Revisions requested: 8 Jun 2009 Revisions received: 14 Oct 2009 Accepted: 4 Dec 2009 Published: 4 Dec 2009
Arthritis Research & Therapy 2009, 11:R181 (doi:10.1186/ar2873)
This article is online at: http://arthritis-research.com/content/11/6/R181
© 2009 Davies-Tuck et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction Given the emerging evidence that osteoarthritis
(OA) may have a vascular basis, the aim of this study was to
determine whether serum lipids were associated with change in
knee cartilage, presence of bone marrow lesions (BMLs) at
baseline and the development of new BMLs over a 2-year period
in a population of pain-free women in mid-life.
Methods One hundred forty-eight women 40 to 67 years old
underwent magnetic resonance imaging (MRI) of their dominant
knee at baseline and 2.2 (standard deviation 0.12) years later.
Cartilage volume and BMLs were determined for both time
points. Serum lipids were measured from a single-morning
fasting blood test approximately 1.5 years prior to the MRI.
Results The incidence of BML at follow-up was associated with
higher levels of total cholesterol (odds ratio [OR] 1.84, 95%
confidence interval [CI] 1.01, 3.36; P = 0.048) and triglycerides
(OR 8.4, 95% CI 1.63, 43.43; P = 0.01), but not high-density
lipoprotein (HDL) (P = 0.93), low-density lipoprotein (LDL) (P =
0.20) or total cholesterol/HDL ratio (P = 0.17). No association
between total cholesterol, triglycerides, HDL, LDL or total
cholesterol/HDL ratio and presence of BMLs at baseline or
annual change in total tibial cartilage volume was observed.
Conclusions In this study of asymptomatic middle-aged women
with no clinical knee OA, serum cholesterol and triglyceride
levels were associated with the incidence of BMLs over 2 years.
This provides support for the hypothesis that vascular pathology
may have a role in the pathogenesis of knee OA. Further work is
warranted to clarify this and whether treatments aimed at
reducing serum lipids may have a role in reducing the burden of
knee OA.
Introduction
The prevalence of vascular disease and cardiovascular risk
factors is high amongst people with osteoarthritis (OA) [1,2].
Emerging evidence suggests that these conditions may share
risk factors [1-5]. Hypercholesterolemia and hypertriglyceri-
demia, both risk factors for cardiovascular disease, have been
related to risk of OA and the progression of OA in epidemio-
logic studies [1-3].
There are a number of mechanisms by which vascular pathol-
ogy may contribute to the development of OA. The ends of
bones are particularly susceptible to vascular insult [6].
Venous occlusion resulting in small-vessel stasis underlying
the cartilage plate, joint hypertension, hypercoagulability and/
or microemboli may all result in subchondral bone ischemia
[3]. The resulting disturbances to subchondral bone nutrition
and repair may impair the supply of nutrients and oxygen to the
overlying cartilage plate [3,7,8]. Bone ischemia may also result
BMI: body mass index; BML: bone marrow lesion; CI: confidence interval; CV: coefficient of variation; HDL: high-density lipoprotein; HDL-C: high-
density lipoprotein cholesterol; LDL: low-density lipoprotein; LDL-C: low-density lipoprotein cholesterol; ln: natural logarithm; MRI: magnetic reso-
nance imaging; OA: osteoarthritis; OR: odds ratio; SD: standard deviation.
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in osteocyte death, leading to bone resorption, which may
reduce the strength of the bony foundation of articular carti-
lage [3,8].
With the advent of magnetic resonance imaging (MRI), it is
now possible to directly visualise joint structures, including
cartilage and bone, in healthy subjects prior to the onset of
OA. While cartilage loss is considered the hallmark of OA and
is associated with symptoms [9] and risk of joint replacement
[10], there is increasing evidence for a significant role of bone
in the pathogenesis of knee OA and it has been suggested
that bone changes may predate cartilage changes [11].
Bone marrow lesions (BMLs) are associated with knee pain
[12-17] and structural changes in the knee in subjects with or
without pain or radiographic OA or both. These include
increased joint space narrowing [18], loss of cartilage [19-21]
and cartilage defects [13,22,23]. BMLs are common in those
with OA, are predominantly associated with malalignment and,
once present, are unlikely to resolve [24-26]. In contrast, in
asymptomatic populations [20,23], their presence is also
associated with systemic factors such as dietary lipids [27]
and they are more likely to resolve [28]. This is perhaps not
surprising given that the histology of BML is heterogeneous
and includes osteonecrosis, oedema, trabecular abnormalities
and bony remodeling [29] and more recently evidence of
ischemia or reperfusion injury or both [8,30]. Given the emerg-
ing evidence that OA may have a vascular basis, the aim of this
study was to explore the relationship between serum lipids
and (a) baseline prevalence of BMLs and (b) annual change in
knee cartilage and incidence of BMLs over a 2-year period in
a population of pain-free middle-aged women.
Materials and methods
One hundred seventy-six women, 40 to 67 years old, were
recruited from an existing cross-sectional study examining
knee structure in women [22]. These women were initially
recruited from a database established from the electoral roll in
Victoria, Australia, between April 2002 and August 2003 [31].
Women were excluded if they had OA as defined by the Amer-
ican College of Rheumatology clinical criteria [32], current or
past knee disease, a history in the past 5 years of knee pain
lasting for more than 24 hours, a previous knee injury requiring
non-weight-bearing treatment for more than 24 hours or sur-
gery (including arthroscopy) or a history of any arthritis diag-
nosed by a medical practitioner or contraindication to MRI.
The study was approved by the Alfred Hospital Human
Research Ethics Committee, and all participants gave written
informed consent.
Anthropometric data and smoking status
The height and weight of each participant were measured at
the time of the original study (2003 to 2005). Body mass index
(BMI) was calculated from these data as weight (in kilograms)
divided by height squared (in metres squared). Smoking status
was determined by questionnaire.
Measurement of blood lipids
Each participant took part in a single-morning fasting blood
test at the time of the original study (2002 to 2003) approxi-
mately 1.53 years (standard deviation [SD] 0.24 years) prior to
their first knee MRI. Fasting bloods drawn at the time of recruit-
ment were stored at -80°C until assayed. Total cholesterol was
determined by the CHOD-PAP (cholesterol oxidase phenol 4-
aminoantipyrine peroxidase) method and triglycerides by the
GPO-PAP (glycerol phosphate oxidase-p-aminophenazone)
method using a Hitachi 747 analyser (Boehringer Mannheim
Systems, now part of Roche Diagnostics, Basel, Switzerland).
High-density lipoprotein cholesterol (HDL-C) was measured
by an enzymatic colorimetric test on a Hitachi 747 analyser.
The assay range is 0.1 to 20 mg/L with intra-assay coefficients
of variation (CVs) of 1.34% at 0.55 mg/L and 0.28% at 12.36
mg/L, interassay CVs of 5.7% at 0.52 mg/L and 2.5% at
10.98 mg/L and a detection limit of 0.03 mg/L [33]. Low-den-
sity lipoprotein cholesterol (LDL-C) was calculated according
to a method previously described [34].
Magnetic resonance imaging and the measurement of
cartilage volume and bone marrow lesion
An MRI of each woman's dominant knee (defined as the lower
limb from which the subject stepped off from when initiating
gait) was performed between October 2003 and August
2004 and approximately 2 years later [22]. Knees were
imaged in the sagittal plane on a 1.5-T whole-body magnetic
resonance unit (Philips Medical Systems, Eindhoven, The
Netherlands) using a commercial transmit-receive extremity
coil. The following sequence and parameters were used: fat-
saturated, gradient echo, three-dimensional, T1-weighted (8
ms/12 ms/55 degrees, repetition time/echo time/flip angle,
slice thickness of 1.5 mm, field of view of 16 cm and matrix of
513 × 196 pixels). In addition, a coronal, T2-weighted, fat-sat-
urated acquisition (repetition time of 2,200 ms, echo time of
20/80 ms, slice thickness of 3 mm, 0.3 interslice gap, one
excitation, field of view of 11 to 12 cm and matrix of 256 × 128
pixels) was obtained.
Assessment of bone marrow lesions
BMLs were defined as areas of increased signal intensity adja-
cent to subcortical bone present in either the medial or lateral
side of the distal femur or proximal tibia assessed from coro-
nal, T2-weighted, fat-saturated images [35]. Two trained
observers, who were blinded to patient characteristics as well
as the sequence of images, together assessed the presence
of lesions for each subject. The presence or absence of a BML
was determined. The reproducibility for determination of the
BML was assessed using 60 randomly selected knee MRI
scans (κ value 0.88, P < 0.001).
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Cartilage volume measurement
The volumes of the individual cartilage plates (medial and lat-
eral tibial) were measured by two blinded assessors from the
total volume by manually drawing disarticulation contours
around the cartilage boundaries on each section on a worksta-
tion, as previously described [9,36], at baseline and approxi-
mately 2 years later. The CVs for the medial and lateral
cartilage volume measures were 3.4% and 2.0%, respectively.
Statistical methods
Variables were assessed for normality. Age, BMI, total choles-
terol, total cholesterol/HDL-C ratio and annual change in car-
tilage volume were all normally distributed; baseline presence
and developing an incident BML compared with 'not' were
binary variables. Annual change in tibial cartilage volume was
calculated by subtracting the follow-up volume from the base-
line volume and then dividing it by the time between MRI
scans. Serum levels of triglyceride, HDL-C and LDL-C were
not normally distributed and therefore the natural logarithms
(ln) were used. Logistic regression was used to determine the
odds of having a prevalent BML at baseline or an 'incident'
BML at follow-up for each of the lipids measured. The potential
confounders of age and BMI were included in the multivariate
model. Linear regression was used to determine the relation-
ship between lipids and annual change in cartilage volume. A
P value of less than 0.05 (two-tailed) was regarded as statisti-
cally significant. All analyses were performed using the SPSS
statistical package (version 15.0.0; SPSS Inc., Chicago, IL,
USA).
Results
One hundred and forty-eight (84%) of the 176 eligible women
completed the 2 year follow up. Apart from being younger (P
= 0.04) there were no significant differences in BMI (P =
0.31), total cholesterol (P = 0.85), (ln)triglycerides (P = 0.82),
(ln)LDL (P = 0.38), (ln)HDL (P = 0.72) and total cholesterol/
HDL ratio (P = 0.45) between those who completed the follow
up and those who did not. Twenty-two (15%) of the population
had a BML present in their knee at baseline. One-hundred
twenty-six women were BML-free at baseline. Of them, 11
(9%) developed an incident BML over the 2-year follow-up. A
comparison of baseline characteristics of the 126 women
(115 who did not develop a BML and 11 who did) is pre-
sented in Table 1.
Serum lipids were not found to be significantly associated with
the presence of BMLs at baseline (Table 2). The relationships
between serum lipids and incidence of BMLs are presented in
Table 3. Incident BMLs were associated with higher total cho-
lesterol and triglyceride concentrations but not HDL-C, LDL-C
or total cholesterol/HDL-C ratio. Only one woman who devel-
oped a BML had ever smoked, so the relationship between
smoking and incident BML could not be examined. The odds
of developing a BML were 1.84 (95% confidence interval [CI]
1.01, 3.36) for every 1 mmol/L increase in total cholesterol
after adjusting for the potential confounders of age and BMI (P
= 0.048). The odds of an incident BML were 8.4 (95% CI
1.63, 43.43) for each unit increase in (ln)triglycerides after
adjusting for confounders (P = 0.01). A trend between
increased odds of incident BMLs and total cholesterol/HDL-C
was also observed (odds ratio [OR] 1.53, 95% CI 0.98 to
2.38; P = 0.06) in univariate analyses, but this relationship did
not reach significance after adjustment for confounders (OR
1.41, 95% CI 0.86 to 2.32; P = 0.17). All analyses were also
performed adjusting for weight rather than BMI, but this did
not alter the results (data not shown).
In addition, when all people who had a BML at either baseline
or follow-up (n = 33) were grouped and compared with those
who had never had a BML (n = 115), we found that the differ-
ence in BMI between the two groups approached significance
with a trend of P = 0.09 (BML group: mean 28.8 mmol/L, SD
6.3; no BML group: mean 26.9 mmol/L, SD 5.4), but there was
no difference in age or gender. Triglyceride levels were also
Table 1
Baseline characteristics of study subjects who did not develop an incident bone marrow lesion compared with those who did
No incident BML
n = 115
Incident BML
n = 11
P value
Age, years 52.3 (6.80)a54.7 (4.98)a0.31b
Body mass index, kg/m226.9 (5.42)b28.9 (5.14)a0.23b
Total cholesterol, mmol/Lc5.71 (3.7-8.3)b6.45 (4.8-9.1)b0.04b
Triglycerides, mmol/Ld1.0 (0.5-2.9)e1.4 (0.8-3.8)e0.01f
HDL, mmol/Lc1.5 (0.5-2.6)e1.3 (0.9-2.6)e0.52f
LDL, mmol/Lc3.6 (1.8-5.8)e3.87 (3.2-6.3)e0.19f
Total/HDL ratio 3.8 (2.0-7.4)a5.3 (2.5-8.3)a0.13b
aMean (standard deviation or range). bIndependent samples t test. cTo convert from mmol/L to mg/dL, divide by 0.0259. dTo convert from mmol/L
to mg/dL, divide by 0.0113. eMedian (range). fMann-Whitney U test. BML, bone marrow lesion; HDL, high-density lipoprotein; LDL, low-density
lipoprotein.
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significantly higher in those with a BML compared with those
who did not have a BML at either time point (median 1.3 mmol/
L, range 0.7 to 3.8, compared with median 1.0 mmol/L, range
0.5 to 2.9; P = 0.02). This persisted after adjusting for age and
BMI (OR 3.28, 95% CI 1.16 to 9.21; P = 0.024).
No association between total cholesterol, triglycerides, HDL-
C, LDL-C, total cholesterol/HDL-C ratio and smoking status
and annual change in total tibial cartilage volume was
observed (Table 4). Similarly, when the medial and lateral com-
partments were analysed separately, no association was seen
(data not shown).
Discussion
In this cohort study of asymptomatic middle-aged women,
serum lipids were not associated with the presence of BMLs
at baseline or change in knee cartilage over 2 years. However,
greater levels of total cholesterol and triglycerides, even within
the normal ranges, were associated with the incidence of
BMLs in knees free of BMLs at baseline.
No previous study has examined the relationship between
serum lipids and longitudinal change in knee structures or inci-
dent OA. There is, however, some evidence suggesting a rela-
tionship between increasing cholesterol and knee OA from
cross-sectional studies [37,38]. Among patients selected
based on hospitalisation for joint replacement due to
advanced OA, approximately 38% had hypercholesterolemia
(serum cholesterol of at least 6.2 mmol/L or on antihyperlipi-
demic medications) [37]. Among women from the Chingford
study, moderately raised serum cholesterol levels (6.0 to 7.1
mmol/L) were associated with the presence of radiological
and bilateral knee OA [38]. In our population of asymptomatic
subjects with no clinically knee OA, we found no significant
relationship between serum lipids and change in cartilage over
2 years.
In contrast, we found a significant relationship between serum
lipids and the development of new BMLs. This finding is sup-
ported by the recent findings in a different asymptomatic pop-
ulation that found that dietary lipids were associated with the
risk of BMLs [27]. Whilst total cholesterol and triglycerides
were associated with the incidence of BMLs, no relationship
was seen with the traditional vascular risk factors of total cho-
lesterol/HDL ratio and LDL. An increased ratio indicates a
higher concentration of the more atherogenic LDL compared
with the HDL cholesterol and confers an increased cardiovas-
cular risk [39]. This may be due in part to the small number of
Table 2
Association between bone marrow lesions at baseline and lipids
Univariate analysis, odds ratio
(95% CI)
P value Multivariate analysis, odds ratio
(95% CI)a
P value
Total cholesterol 0.91 (0.62, 1.33) 0.63 0.9 (0.6,1.35) 0.61
Ln triglycerides 1.99 (0.77, 5.16) 0.15 1.81 (0.63, 5.20) 0.27
Ln HDL 0.45 (0.09, 2.12) 0.31 0.63 (0.11, 3.50) 0.6
Ln LDL 0.65 (0.15, 2.90) 0.58 0.58 (0.12, 2.80) 0.50
Total/HDL ratio 1.10 (0.81, 1.50) 0.54 1.03 (0.73, 1.43) 0.88
aOdds ratio of having a bone marrow lesion present at baseline for each unit increase in total cholesterol, natural logarithm (Ln) of triglycerides,
natural logarithm of high-density lipoprotein (HDL) or low-density lipoprotein (LDL) or for the total/HDL ration after adjusting for age and body
mass index. CI, confidence interval.
Table 3
Association between incident bone marrow lesions and lipids
Univariate analysis, odds ratio
(95% CI)
P value Multivariate analysis, odds ratio
(95% CI)a
P value
Total cholesterol 1.82 (1.04, 3.2) 0.037 1.84 (1.01, 3.36) 0.048
Ln triglycerides 9.23 (2.06, 41.46) 0.004 8.4 (1.63, 43.43) 0.01
Ln HDL 0.60 (0.06, 5.99) 0.67 1.12 (0.008, 14.79) 0.93
Ln LDL 7.10 (0.56, 89.39) 0.13 5.79 (0.39,86.46) 0.20
Total/HDL ratio 1.53 (0.98, 2.38) 0.06 1.41 (0.86, 2.32) 0.17
aOdds ratio of having an incident bone marrow lesion for each unit increase in total cholesterol, natural logarithm (Ln) of triglycerides, natural
logarithm of high-density lipoprotein (HDL) or low-density lipoprotein (LDL) or for the total/HDL ration after adjusting for age and body mass index.
CI, confidence interval.
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incident BMLs reducing the power of the study to detect
weaker associations, as was seen in the demonstrated rela-
tionships between incident BML and total cholesterol/HDL
ratio, in which a significant univariate trend that was not per-
sistently significant in the multivariate analyses was shown.
Although we did not detect any significant associations
between lipid levels and prevalent BMLs at baseline, this may
be explained by the mixed nature of BMLs. To date, a number
of risk factors have been identified for BMLs; one predominant
risk factor is malalignment [18]. Prevalent BMLs are likely to be
a diverse group and the result of a number of risk factors,
including altered joint biomechanics and trauma as well as
other known and unknown factors. Therefore, the ability to
identify a risk factor such as serum lipids, independent of other
risk factors, may be reduced among those with prevalent
BMLs. In contrast, by examining those free of BMLs at base-
line in this population of asymptomatic people with no clinical
knee disease or symptoms, we were able to detect a relation-
ship between serum lipids and incident BMLs. This longitudi-
nal finding provides a much stronger level of evidence for a
relationship between serum lipids and BMLs than can be
obtained from a cross-sectional study [40]. Our data suggest
that BMLs are not solely a consequence of biomechanical fac-
tors. It is possible that the relationship between lipids and
BMLs may be a consequence of vascular pathology. Subchon-
dral bone is highly vascularised and it has been suggested that
one origin of BMLs may be ischemia and/or reperfusion injury
[8]. A study of human bone marrow using gadolinium demon-
strated that compared with knees free of BMLs, those with
BMLs showed perfusion abnormalities, including significantly
reduced venous outflow [30], and BMLs detected on MRI
have been said to be similar to those seen in avascular necro-
sis [7].
Although some previous studies have suggested that hyperli-
pidemia may occur as a consequence of OA and the associ-
ated treatments, the findings of our study suggest that this is
not the case but that serum cholesterol and triglycerides are
positively associated with structural change in the knee in the
absence of OA. Whether elevated lipid levels cause incident
BMLs via a vascular mechanism is not known. Alternatively, it
may be that the relationship between serum lipids and inci-
dence of BMLs is the result of inflammatory pathways or as yet
unknown mechanisms. Given that coagulation and inflamma-
tory pathways have been shown to be intimately related [41],
it is possible that the results we have observed are a combina-
tion of both effects. Histological studies in both animals and
humans have demonstrated lipid, cholesterol and fibrin depos-
its in cancellous bone [41-43]. These lipid emboli and thrombi
may result in reduced blood flow and lead to ischemia and ulti-
mately bone necrosis. Furthermore, dogs with hip OA were
shown to have increased serum lipid levels as well as evidence
of hypofibrinolysis and increased platelet aggregability that
could be reversed with treatment, resulting in a significant
improvement in OA symptoms [41]. Thus, it may be that reduc-
ing lipids will have a beneficial effect in reducing subsequent
knee OA.
Hypercholesterolemia and hypertriglyceridemia are major risk
factors for cardiovascular disease in women [44]. We have
found that subtle perturbations in lipid metabolism are also
associated with the development of new BMLs, which are sig-
nificant predictors of OA development and progression. We
did not find a significant association between serum lipids and
cartilage change. However, given that BMLs are associated
with progression of cartilage defects [45] and loss of cartilage
[19-21], it may be that our present study did not have power
to show a direct relationship between serum lipids and carti-
lage loss. Larger studies of longer duration, especially in an
asymptomatic population free of clinical OA, may be required.
This study has a number of limitations. First, the power of this
study to show an effect was limited by the low number of prev-
alent (14%) BMLs; therefore, we were unable to examine
change in BML size over 2 years. In addition, due to the mod-
est number of subjects who developed a BML, these results
will need to be confirmed in larger studies. In this study, we
were not able to measure knee alignment and this may have
attenuated our findings. However, recent work suggests that
the relationship between BML and progression persisted after
Table 4
Association between lipids and annual change in total tibial cartilage volume
Univariate analysis, regression coefficient
(95% CI)
P value Multivariate analysis, regression coefficient
(95% CI)a
P value
Total cholesterol -0.24 (-12.77, 12.28) 0.97 -1.77 (-11.35, 14.88) 0.79
Ln triglycerides 0.70 (-32.48, 33.88) 0.97 12.6 (-24.12, 49.32) 0.49
Ln HDL -4.78 (-56.43, 46.88) 0.85 -15.96 (-72.28, 40.37) 0.58
Ln LDL 3.16 (-48.06, 54.39) 0.90 13.12 (-41.2, 67.45) 0.63
Total/HDL ratio -0.67 (-11.57, 10.24) 0.90 2.58 (-9.5, 14.68) 0.67
aAnnual change in total tibial cartilage volume (in microlitres) for each unit increase in total cholesterol, natural logarithm (Ln) of triglycerides,
natural logarithm of high-density lipoprotein (HDL) or low-density lipoprotein (LDL) or for the total/HDL ratio after adjusting for age and body mass
index. CI, confidence interval.
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accounting for alignment [18]. In addition, due to the low prev-
alence of smokers in this population, we were unable to exam-
ine how smoking may relate to loss of cartilage and incidence
of BMLs. We did not obtain radiographs of the knees, so some
subjects may have had asymptomatic radiographic OA. How-
ever, we used the presence of pain to exclude any potential
participants who may have had clinical OA since all of the
American College of Rheumatology criteria for the classifica-
tion of knee OA require pain. Individuals with significant knee
injury in the past, pain at baseline, knee surgery or physician
diagnosis of any type of arthritis were excluded. There is
debate as to how to define early knee OA since it is now clear
that there is a continuum from the normal to the OA knee, with
more than 10% of knee cartilage already lost by the time radi-
ological OA is present [46]. A major strength of our findings is
that serum lipids were shown to be a risk factor for incident
BML among those without any BML at baseline in a population
that was asymptomatic with no knee pain, no history of treat-
ment for knee disease and no history of knee injury. This pop-
ulation represents an asymptomatic preclinical OA population
within the spectrum of disease development and would be the
population in which primary prevention measures would be
used. Another potential limitation of our study is that lipids
were measured 1.5 to 3.5 years prior to the MRI assessment.
However, baseline measurements of lipoprotein lipids and
apoproteins have been shown to be robust predictors of car-
diovascular events a number of years later [47]. We also did
not have information on whether women were on lipid-lower-
ing drugs; however, the aim of this study was to examine the
relationship between serum lipid levels and BMLs and carti-
lage. Any woman on treatment would have been classified
based on her cholesterol level; therefore, those with a ten-
dency to hypercholesterolemia but whose cholesterol was
normal on assessment would have been analysed as having a
normal cholesterol level. This is likely to have underestimated
the effect we observed.
Conclusions
In this study of asymptomatic middle-aged women with no clin-
ical knee OA, cholesterol and triglyceride levels were associ-
ated with the incidence of BMLs over 2 years. This provides
support for the hypothesis that vascular pathology may have a
role in the pathogenesis of knee OA and warrants further work
to clarify this and whether treatments aimed at reducing serum
lipids may have a role in reducing the burden of knee OA.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
FH, SRD, SLD and JA were involved in the design and imple-
mentation of the study, including data collection and measure-
ment. AEW, RJB and FMC were involved in the design and
implementation of the study, including data collection and
measurement, and in the analysis and interpretation of the
data. MD-T was involved in the analysis and interpretation of
the data. All authors were involved in the manuscript prepara-
tion and read and approved the final manuscript.
Acknowledgements
This work was supported by grants from the National Health and Medi-
cal Research Council of Australia (NHMRC) (grants 219279 and
334267). AEW and FH are the recipients of NHMRC Public Health
(Australia) Fellowships (317840 and 418961, respectively). We would
especially like to thank the study participants, who made this study pos-
sible.
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... 5 Some studies have linked elevated blood lipids and osteoarthritic changes. 6 The use of bicarbonate and sulphate-sulphide mineral water by drinking under controlled conditions could lower blood lipid levels. [7][8][9] The exact mechanism of antilipemic action of these mineral waters is unknown. ...
... 5 In a 2009 study of 148 middle-aged women without clinical signs of gonarthrosis and with reference cholesterol and triglyceride values, Davies et al found an increased number of women with osteoarthritis who had low and elevated serum lipids after two years. 6 The treatment of patients with dyslipidaemias is complex and requires a multidisciplinary approach. Physiological treatment of patients with gonarthrosis can affect the level of reduction of serum lipids in several ways. ...
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... Several studies have reported a possible association between knee OA and TG levels, albeit that none of these associations reached statistical significance [10,34,35]. In our study, expression of MMPs and ADAMTSs did not differ between patients with low and high TG levels. ...
... In our study, expression of MMPs and ADAMTSs did not differ between patients with low and high TG levels. Corroborating previous findings [10,34,35], our study suggests that the presence of hypertriglyceridemia has less influence on the glenohumeral joint. ...
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