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The determinants of change in patella cartilage volume—a cohort
study of healthy middle-aged women
S. P. Wijayaratne1,Ã
, A. J. Teichtahl1,Ã
, A. E. Wluka1,2
, F. Hanna1
, R. Bell3
, S. R. Davis3
, J. Adams3
and
5 F. M. Cicuttini1
Objectives. Although cartilage loss occurs with advancing age and is a hallmark of OA, the factors that affect cartilage change are not well
established. The aim of this study was to explore the determinants of change in patella cartilage volume over 2 yrs among healthy middle-
aged women with no clinical knee OA.
Methods. One hundred and forty-eight women with no clinical knee OA were recruited from a previous population-based cross-sectional
10 study of healthy women aged 40–67 yrs. MRI was performed at baseline and at 2 yrs, to assess patella cartilage and bone volume. Self-
reported exercise was assessed by questionnaire.
Results. Annual loss of patella cartilage volume was 1.6% (95% CI 1.2, 1.9). Age was positively associated with patella cartilage volume loss
after adjustment for confounders (P ¼ 0.05). For every 1 mm3
increase in patella bone volume at baseline, annual cartilage loss was reduced
by 8.05 mm3
(95% CI 12.91, 3.19; P < 0.001). Fortnightly participation in exercise promoting an increased heart and respiratory rate for at
15 least 20 min also tended to be associated with a reduced rate of patella cartilage volume loss (P ¼ 0.09).
Conclusion. Among middle-aged women with no clinical knee OA, advancing age expedites the rate of patella cartilage volume loss,
while increased patella bone volume and exercise participation tends to be associated with a reduction in the rate of patella cartilage volume
loss. Interventions targeting modifiable factors, such as physical activity, warrant further investigation as they may help to prevent
patellofemoral OA.
20 KEY WORDS: Patella, Cartilage, Bone, Osteoarthritis, Knee.
Introduction
Knee OA is a common, painful and debilitating disease that
increases in prevalence with age and is more common in women
than men after mid-life [1]. Although the majority of epidemiol-
25 ogical studies examining knee joint structures in either health or
disease have predominantly focused on the tibiofemoral rather
than the patellofemoral compartment [2], there is increasing evi-
dence implicating the patellofemoral compartment as a major
source of pain and disability [3–5].
30 A reduction in cartilage volume, assessed either radiographi-
cally via joint space narrowing, or directly via MRI, remains the
predominant outcome measure in studies examining the natural
history of knee OA [6]. Recent data from MRI studies have
suggested that a reduction in knee cartilage volume occurs prior to
35 the onset of radiographic knee OA [7–11]. It has been shown that
even in the absence of OA, patella cartilage volume is reduced at
an annual rate of 2.1% among older adults [12]. However, the
factors that affect patella cartilage change are unclear.
The aim of this study was to determine whether age, weight,
40 physical activity and features of patellofemoral joint structure,
such as patella bone volume, affect the rate of patella cartilage loss
in healthy middle-aged women with no clinical knee OA over 2 yrs.
Participants and methods
The women in this study were a sub-group recruited from a larger
45 group of 1423 community-based women who participated in a
previous study examining the role of androgens in women [13].
The original group of 1423 was recruited between April 2002 and
August 2003 from a database established from the electoral roll in
the southern Australian state of Victoria [13]. The database was
50established using household addresses selected at random on a
weekly basis from Australian electoral areas. In Australia, because
voting is compulsory, every adult must be registered on the
electoral roll. Each electoral area was divided into sampling points
of approximately equal numbers of 25 000 each. Melbourne had
55105 sampling points, and country Victoria had 43 sampling points.
Starting addresses were selected at random from the electoral roll
for each of the sampling points. Women were recruited from the
database by telephone and were excluded from participation if
they were pregnant or <6 weeks post-partum or had experienced
60any of the following in the preceding 3 months: an acute psychi-
atric illness; acute renal, liver, cardiovascular disease or any other
acute major illness; gynaecological surgery; or active malignancy
or cancer treatment, excluding non-melanotic skin cancer [13].
Of the 1423 participants aged 18–75 yrs, who participated in the
65original study, 292 women met the inclusion criteria for the
current study, including being in the desired age range (40–67 yrs),
not having had a hysterectomy or past history of cancer and
having agreed to be recontacted about participation in further
research studies. Women were further excluded for the current
70study if they had a history of previous significant knee injury
requiring non-weight-bearing treatment for >24 h or surgery
(including arthroscopy), evidence of radiographic OA, osteoporo-
sis and contraindications to MRI including having a pacemaker,
metal sutures, presence of shrapnel or iron filings in an eye. One
75hundred and seventy-six women underwent a baseline MRI scan
on their dominant knee (defined as the knee the subject stepped
off from when initiating walking from rest) between October 2003
and August 2004. Alfred Human Research Ethics Committee
approved the study and all participants gave written informed
80consent.
Subjects completed a questionnaire that included demographic
data, past medical and surgical history and current participation
levels of physical activity at their baseline visit [14]. Participation
in fortnightly exercise was assessed by asking whether or not a
1
Department of Epidemiology and Preventive Medicine, Monash University
Medical School, Alfred Hospital, Prahran, Victoria 3181, 2
Baker Heart Research
Institute, Commercial Road, Melbourne, Victoria 3004 and 3
Department of
Medicine, The Women’s Health Program, Monash University Medical School,
Alfred Hospital, Prahran, Victoria 3181, Australia.
Submitted 2 January 2008; revised version accepted 5 June 2008.
Correspondence to: F. M. Cicuttini, Department of Epidemiology and Preventive
Medicine, Monash University Medical School, Alfred Hospital, Prahran, Victoria
3181, Australia. E-mail: flavia.cicuttini@med.monash.edu.au
Ã
S. P. Wijayaratne and A. J. Teichtahl equally contributed to this work.
Rheumatology 2008; 1 of 4 doi:10.1093/rheumatology/ken244
258
1 of 4
ß The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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subject had undertaken at least 20 min of exercise that was severe
enough to raise their heart or respiratory rate (e.g. bicycling, brisk
walking, jogging, aerobics, etc.). From these data, a nominal scale
was created to indicate exercise participation (yes/no). Weight was
5 measured to the nearest 0.1 kg using a single pair of electronic
scales with shoes, socks and bulky clothing removed. Height was
measured to the nearest 0.1 cm using a stadiometer with shoes and
socks removed. BMI [weight (kg)/height2
(m2
)] was calculated.
At baseline, each woman had an MRI performed on her
10 dominant knee. This was re-imaged $2 yrs later. Knees were
imaged in the sagittal plane on the same 1.5-T whole body
magnetic resonance unit (Signa Advantage HiSpeed GE Medical
Systems Milwaukee, WI, USA) using a commercial receive-only
extremities coil. The following sequence and parameters were
15 used: a T1-weighted fat-suppressed 3D gradient recall acquisition
in the steady state; flip angle 558; repetition time 58 ms; echo time
12 ms; field of view 16 cm; 60 partitions; 512 Â 192 matrix; one
acquisition time 11 min 56 s. Sagittal images were obtained at a
partition thickness of 1.5 mm and an in-plane resolution of
20 0.31mm  0.83mm (512  192 pixels). Patella cartilage volumes
and patellar bone volume were determined by means of image
processing on an independent work station using the software
program Osiris as previously described [15, 16]. A single reader
measured all the MRI, blinded regarding the time sequence of the
25 MRI. The coefficients of variation (CVs) were 2.1% for patella
cartilage volume and 2.4% for patella bone volume [17, 18].
The principal outcome variables assessed were annual rate of
patella cartilage volume loss: [(initial volumeÀsecond volume)/
(time between scans)] and annual percentage loss of patella car-
30 tilage volume: [(initial volumeÀsecond volume)/(initial volume)
(time between scans) Â 100%].
Statistical analysis
With a sample size of 148 participants from the cohort we had a
power of 80% to show a correlation as low as 0.2 between the
35 various risk factors and a change in patellar cartilage volume,
taking into account that multiple variables were going to be
examined (-error 0.05, two-sided significance). Descriptive
statistics for characteristics of the subjects were tabulated.
Independent t-tests and chi-square tests or Fisher’s exact test
40 (where appropriate) were used to compare characteristics between
the study sample and the subjects lost to follow-up. A single
sample t-test was used to determine whether the rate of change
observed was significantly different from zero. Determinants of
change in patella cartilage volume including age, body height,
45 weight, initial patella cartilage and patella bone volume and
exercise participation were assessed using linear regression
analysis, and potential confounders adjusted for in a multivariate
analysis. P-values of 0.05 (two-tailed) were regarded as
statistically significant (SPSS Version 14.0).
50Results
The characteristics of the study population are presented in
Table 1. One hundred and forty-eight of the original 176 subjects
completed the longitudinal MRI component. Twenty-eight of the
176 subjects were lost to follow-up because of death (n ¼ 1),
55migration (n ¼ 1), knee injury (n ¼ 4), surgery (n ¼ 1), withdrawal
of consent (n ¼ 3) and being unable to be contacted (n ¼ 18).
Although the subjects that were lost to follow-up were signifi-
cantly younger than those who completed the study (mean Æ S.D.,
52.8 Æ 6.6 vs 49.5 Æ 6.3 yrs; P ¼ 0.01), there were no significant
60differences in terms of weight, body height, BMI, baseline patella
cartilage volume, patellar bone volume and fortnightly exercise
participation between the two groups (data not shown).
The annual rate of patella cartilage volume loss was 35 mm3
(95% CI 26.7, 43.2), which is equivalent to 1.6% (95% CI 1.2, 1.9)
65per annum (Table 2). Of the subjects, 79.7% had participated in at
least 20 min of exercise that was severe enough to raise their heart
or respiratory rate.
In univariate analysis, age was not associated with the annual
rate of patella cartilage volume loss (P ¼ 0.20) (Table 3). However,
70after adjustment for body height, weight, initial patella cartilage
and bone volume, age was positively associated with the annual
rate of patella cartilage volume loss (P ¼ 0.05). Patella bone
volume was negatively associated with the annual rate of patella
cartilage volume loss in both univariate (P ¼ 0.02) and multivariate
TABLE 1. Characteristics of the study population
Total n ¼148
Age (yrs) 52.8 (6.6)
Body height (cm) 163.7 (6.5)
Weight (kg) 72.9 (14.9)
BMI [weight (kg)/height2
(m2
)] 27.3 (5.7)
Patella cartilage volume at baseline (ml) 2.5 (0.5)
Patella bone volume baseline (ml) 12.9 (1.9)
Participation in fortnightly exercise
significant enough to increase heart
and respiratory rate for !20 min (%)
118 (79.7)
All values are presented as mean (S.D.), except for percentages.
TABLE 2. Rate of patella cartilage change in the cohort
Mean (95% CI) P-valueÃ
Annual rate of
patella cartilage
volume loss (mm3
)
35.0 (26.7, 43.2) 0.001
Annual percentage
loss of patella
cartilage volume (%)
1.6 (1.2, 1.9) 0.001
Ã
A single-sample t-test was used to calculate P-values.
TABLE 3. Factors affecting annual rate of patella cartilage volume loss
Univariate regression
coefficient (95% CI) P-value
Multivariate regression
coefficienta
(95% CI) P-value
Ageb
(yrs) 0.82 (À0.44, 2.07) 0.20 1.27 (À0.02, 2.55) 0.05
Patella bone volumec
(ml) À3.50 (À6.34,À0.65) 0.02 À8.92 (À14.45, À3.40) 0.001
Weightd
(kg) À0.38 (À0.95, 0.20) 0.20 À0.30 (À0.87, 0.26) 0.29
Body heighte
(cm) À0.45 (À1.73, 0.83) 0.49 0.78 (À0.75, 2.31) 0.31
Participation in fortnightly exercise that promoted
an increased heart and respiratory
rate for at least 20 minf
À17.12 (À37.54, 3.29) 0.10 À17.43 (À37.74, 2.88) 0.09
a
Multivariate analysis with age, body height, weight, patella bone and initial patella cartilage volume in the regression equation.
b
Annual rate of change in patellar cartilage volume (mm3
) per year increase in age.
c
Annual rate of change in patellar cartilage volume (mm3
) per millilitre increase in patella bone volume.
d
Annual rate of change in patellar cartilage volume (mm3
) per kilogram increase in weight.
e
Annual rate of change in patellar cartilage volume (mm3
) per centimetre increase in body height.
f
Annual rate of change in patella cartilage volume (mm3
) for subjects participating in fortnightly exercise significant enough to raise the heart and respiratory rate for at least 20 min.
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(P 0.001) analyses. Initial patella cartilage volume, body
height and weight were not significantly associated with the
annual rate of patella cartilage volume loss.
Participation in exercise (yes/no) that promoted an increased
5 heart and respiratory rate for at least 20 min in the previous
fortnight was not significantly associated with annual rate of
patella cartilage volume loss in univariate analysis, but tended
towards association after adjustment for age, height, weight, initial
patella cartilage volume and patella bone volume (P ¼ 0.09).
10 Discussion
In this 2-yr study of middle-aged women with no clinical knee OA,
patella cartilage volume was lost at an annual rate of 1.6% (95%
CI 1.2, 1.9%). Advancing age was shown to expedite the annual
rate of patella cartilage loss. Conversely, increased patella bone
15 volume at baseline was associated with a reduced annual rate of
patella cartilage volume loss and there was a trend towards an
inverse relationship between fortnightly participation in exercise
that caused an increased heart and respiratory rate for at least
20 min and the annual rate of patella cartilage volume loss.
20 In our cohort of healthy middle-aged women, the average
annual rate of patella cartilage volume loss was 1.6%, which is
similar to a smaller longitudinal study of healthy middle-aged men
and women, where the average rate of patella cartilage loss was
2.1% per year (95% CI 1.1, 3.2%) [12]. However, in the presence
25 of OA, patella cartilage volume is lost more rapidly, with between
3.5% and 5.3% of total cartilage volume lost annually [19].
Among healthy women, we have shown that advancing age
expedites the rate of patella cartilage volume loss. Although
previous cross-sectional studies have demonstrated a reduction in
30 patella cartilage volume [20, 21] and progressive cartilage thinning
[22] with advancing age, this longitudinal study is the first to
demonstrate that advancing age is associated with an increased
rate of patella cartilage volume loss.
No previous study has examined the relationship between
35 patella bone volume and patella cartilage volume loss. At the
tibiofemoral joint, recent evidence has suggested that bony
enlargement may be an important factor initiating cartilage
degeneration, whereby larger tibial plateau bone area at baseline
was associated with more severe tibial cartilage defects over a 2-yr
40 period [23], as well as reduced knee cartilage volume [24]. In the
current study, we have demonstrated that baseline patella bone
volume was associated with a reduced rate of annual patella
cartilage volume loss. Due to the difficulties associated with
assessing the undersurface of the irregular patella, we have
45 measured patella bone volume, rather than the surface area of the
bony patella. The reasons for the differences observed between the
tibial and patella cartilage change in relation to bone size may be
due to the biomechanical differences acting across the two knee
compartments. As tibial plateau surface area expands, articular
50 cartilage is effectively spread over a greater surface area and is
subject to axial loads, which may make cartilage more prone to
degeneration. The patella, however, is subject to retropatellar and
shearing forces throughout knee range of movement, which may
predominantly mediate bone volume enlargement without sig-
55 nificantly changing the articular surface area of the patella. In
turn, the patella cartilage may not be required to conform to a
larger articular surface area and may establish a mechanical
environment that reduces cartilage degeneration. Moreover, the
increased synthetic activity required for increased bone volume
60 may protect against cartilage loss, and Wang et al. [25] showed
that higher baseline serum levels of osteocalcin were associated
with a decreased rate of knee cartilage loss.
In this study, there was also a trend towards an inverse
association between self-reported fortnightly participation in
65 exercise that caused an increased heart and respiratory rate for
at least 20 min and a reduced rate of annual patella cartilage
volume loss. Previous work has shown that physical activity data
yielded from questionnaires similar to the one used in this study
yields data that is comparable with activity levels over the
70previous 3 yrs [26]. Using this questionnaire, we recently
demonstrated a positive association between fortnightly exercise
participation and medial tibial cartilage volume among these
women [27]. Moreover, we have demonstrated that increased
tibial cartilage volume was associated with more frequent and
75longer durations of vigorous activity (activity leading to diaphor-
esis or dyspnoea) reported 10 yrs previously, as well as recent
vigorous activity in the 7 days prior to MRI [28]. This study’s
results also support a beneficial effect of physical activity, this
time at the patellofemoral joint, by demonstrating a trend towards
80association between exercise participation and a reduction in the
rate at which patella cartilage volume is lost.
Why fortnightly exercise participation tended to be associated
with a reduced rate of patella cartilage volume loss is unclear. This
effect could not be explained by an increase in patella bone
85volume or younger age, since our results were independent of
these factors. It is well recognized that some degree of mechanical
stimulation is required to maintain cartilage health [29], and
exercise may mediate an optimal mechanical environment. Other
cross-sectional and longitudinal studies in children have shown
90that tibial cartilage development is stimulated by exercise [30, 31],
while in adults, forced immobility is associated with marked
reductions in cartilage volume at the knee [32]. Nevertheless,
future longitudinal investigations are required to clarify the type,
frequency, intensity and duration of exercise required to confer a
95beneficial effect across the knee joint.
This study was limited by the examination of healthy women,
and therefore our results cannot be generalized to men or people
with knee OA. Moreover, 16% of women with a baseline MRI did
not complete the study. The women who did not have follow-up
100MRI were younger than those who were retained in the study. As
the most common reason for not attending for MRI at follow-up
was an inability to be recontacted, it is unlikely that the loss of
women from this study would have introduced any systematic bias
into the study findings. Although we were able to detect a
105significant rate of patella cartilage loss, we only examined women
over a relatively short period (2 yrs), and longer studies would be
needed to examine the effect of factors that may have a weaker
effect on the rate of change of patella cartilage volume. Although
we showed a protective effect of exercise participation and the rate
110of patella cartilage volume loss, based on the questionnaire used in
this study, we cannot distinguish between weight-bearing and non-
weight-bearing exercises, and therefore cannot determine whether
weight-bearing exercises are more advantageous than non-weight-
bearing exercises for the patella cartilage. Furthermore, we did not
115examine participation in exercises of varying intensity, duration
and frequency, all of which may be important.
We have shown that among middle-aged women with no
clinical knee OA, patella cartilage volume is lost at 1.6% per
annum. Although older age was associated with an increased
120annual rate of patella cartilage volume loss, increased patella bone
volume at baseline was associated with a reduced annual rate of
patella cartilage volume loss. Moreover, fortnightly participation
in exercise that promoted an increased heart and respiratory rate
for at least 20 min tended to be associated with a reduced rate of
125cartilage loss. Interventions targeting modifiable factors, such as
physical activity, warrant further investigation as they may help to
prevent the development of patellofemoral OA.
Rheumatology key messages
Advancing age expedites the rate of patella cartilage volume loss.
Increased patella bone volume and exercise participation tend to
retard the rate of patella cartilage volume loss.
Interventions targeting modifiable factors, such as physical
activity, may help to prevent patellofemoral OA.
Change in patella cartilage volume 3 of 4

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Acknowledgements
The authors would like to thank the women who took part in this
study.
Funding: This work was supported by grants from the National
5 Health and Medical Research Council of Australia (grants
number 219279 and 334267). A.E.W. is the recipient of an
NHMRC Public Health (Australia) Fellowship (NHMRC
317840). F.H. is the recipient of an NHMRC Public Health
(Australia) Fellowship (NHMRC 418961).
10 Disclosure statement: The authors have declared no conflicts
of interest.
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