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com
549

EXTENDED REPORT

Association between age and knee structural change: a

cross sectional MRI based study
C Ding, F Cicuttini, F Scott, H Cooley, G Jones
...............................................................................................................................
Ann Rheum Dis 2005;64:549–555. doi: 10.1136/ard.2004.023069

Objective: To describe the associations between age, knee cartilage morphology, and bone size in adults.
Methods: A cross sectional convenience sample of 372 male and female subjects (mean age 45 years,
range 26–61) was studied. Knee measures included a cartilage defect five site score (0–4 respectively) and
prevalence (defect score of >2 at any site), cartilage volume and thickness, and bone surface area and/or
volume. These were determined at the patellar, medial, and lateral tibial and femoral sites using T1
weighted fat saturation MRI. Height, weight, and radiographic osteoarthritis (ROA) were measured by
standard protocols.
Results: In multivariate analysis, age was significantly associated with knee cartilage defect scores
(b = +0.016 to +0.073/year, all p,0.01) and prevalence (OR = 1.05–1.10/year, all p,0.05) in all
See end of article for compartments. Additionally, age was negatively associated with knee cartilage thickness at all sites
authors’ affiliations (b = 20.013 to 20.035 mm/year, all p,0.05), and with patellar (b = 211.5 ml/year, p,0.01) but not
.......................
tibial cartilage volume. Lastly, age was significantly positively associated with medial and lateral tibial
Correspondence to: surface bone area (b = +3.0 to +4.7 mm2/year, all p,0.05) and patellar bone volume (b = +34.4 ml/
Associate year, p,0.05). Associations between age and tibiofemoral cartilage defect score, cartilage thickness, and
Professor G Jones,
Menzies Research Institute, bone size decreased in magnitude after adjustment for ROA, suggesting these changes are directly
Private Bag 23, Hobart, relevant to OA.
Tasmania 7000, Australia; Conclusion: The most consistent knee structural changes with increasing age are increase in cartilage
g.jones@utas.edu.au
defect severity and prevalence, cartilage thinning, and increase in bone size with inconsistent change in
Accepted 12 August 2004 cartilage volume. Longitudinal studies are needed to determine which of these changes are primary and
....................... confirm their relevance to knee OA.

O
steoarthritis (OA) is a major public health problem. It association between age, knee cartilage defects, and knee
is well established that age1 2 is a strong risk factor for bone size (which can be measured as tibial cross sectional
knee OA, but the underlying mechanism remains area and patella bone volume). This study, therefore, aimed
obscure. Whereas tensile stiffness of knee and hip, and to a at describing the association between age, knee cartilage
lesser extent, ankle articular cartilage3 4 and proteoglycan defects, volume, thickness, and bone size in a large con-
content,5 decrease with age, advanced glycation end pro- venience sample of adult men and women.
ducts6 and cartilage turnover markers7 8 increase with age.
These biomechanical and biochemical changes in articular PATIENTS AND METHODS
cartilage may have a role in age related OA, but age related Subjects
morphological alterations in articular cartilage and subchon- The study was carried out in Southern Tasmania, primarily in
dral bone are potential further explanations for OA. the capital city of Hobart, from June 2000 until December
Radiographic assessment as a surrogate measure of 2001. The primary aim was to examine the genetic mechan-
articular cartilage has provided inconsistent results. Knee isms of knee OA using a matched design. It was approved by
joint space area9 and width10 appear to decrease with age, the Southern Tasmanian Health and Medical Human
while incident knee joint space narrowing in middle aged Research Ethics Committee and all subjects provided
women11 and joint space width in normal knees is incon- informed written consent.
sistently associated with age.9 12 This inconsistency may A convenience sample was used for this study. Subjects
reflect what actually happens or reflect the two dimensional were selected from two sources. Half of the subjects were the
nature of radiographic measurement and the variability in adult children of subjects who had had a knee replacement
measurement introduced by factors such as joint position. performed for primary knee OA at any Hobart hospital in the
Furthermore, the radiographic joint space consists not only of years 1996–2000 (offspring). This diagnosis was confirmed by
articular cartilage but also menisci. reference to the medical records of the orthopaedic surgeon
Magnetic resonance imaging (MRI) can visualise joint and the original radiograph where possible. The other half
structure directly and is recognised as a valid, accurate, and were randomly selected controls. These were selected by
reproducible tool to measure articular cartilage defects,13–15 computer generated random numbers from the most recent
volume, thickness, and bone surface area.16–19 However, the version of the electoral roll (2000). Subjects from either group
results from early MRI studies on the association between were excluded on the basis of contraindication to MRI
age and knee cartilage volume and thickness are contra- (including metal sutures, presence of shrapnel, iron filing in
dictory, possibly owing to the small sample size in these eye, and claustrophobia). No women were receiving hormone
studies.20–23 The largest of these studies23 reported a sub- replacement therapy at the time of the study.
stantial decrease in thickness of cartilage in the knee at all
sites, although this did not reach statistical significance at Abbreviations: MRI, magnetic resonance imaging; OA, osteoarthritis;
the tibia. Furthermore, there is little information on the ROA, radiographic osteoarthritis

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550 Ding, Cicuttini, Scott, et al

Table 1 Characteristic of participants

Age ,45 years Age >45 years
(n = 167) (n = 205) p Value

Female (%) 57 58 0.822*

Height (cm) 167.6 (7.6) 168.6 (8.8) 0.247
Weight (kg) 76.5 (15.4) 78.3 (15.3) 0.245
Body mass index (kg/m2) 26.5 (4.7) 27.5 (4.6) 0.046
Radiographic osteoarthritis (%) 10 23 0.001*
Medial joint space narrowing (%) 9 18 0.01*
Lateral joint space narrowing (%) 0 5 0.004*
Medial osteophytes (%) 2 8 0.014*
Lateral osteophytes (%) 1 3 0.252*
Knee pain (%) 34 35 0.875*
Knee injury history (%) 19 20 0.932*
Smoking (%) 54 55 0.813*

Values are shown as mean (SD) except for percentages.

*Determined by Mann-Whitney U test, all others by t test.

Anthropometry lateral tibial plateau bone area was determined by creating an

Weight was measured to the nearest 0.1 kg (with shoes, isotropic volume from the three input images closest to the
socks, and bulky clothing removed) using a single pair of knee joint. This method does not take tibial curvature into
electronic scales (Seca Delta Model 707), which were account and is a composite measure of the subchondral plate
calibrated using a known weight at the beginning of each and cancellous bone. The coefficient of variation for all
clinic. Height was measured to the nearest 0.1 cm (with measures was 2.1–2.6%.17 18
shoes and socks removed) using a stadiometer. Knee pain
was assessed by the questionnaire and was defined as pain Cartilage defect assessment
for .24 hours in the past 12 months or daily pain on more The cartilage defects were graded on the above MR images
than 30 days in the past year. with a modification of a previous classification system13–15 at
the medial tibial, medial femoral, lateral tibial, lateral
Radiographs femoral, and patellar sites as follows: grade 0, normal
A standing anteroposterior semiflexed view of the right knee cartilage; grade 1, focal blistering and intracartilaginous low
was performed in all subjects. The angle was kept to 10–15 signal intensity area with an intact surface or bottom; grade
degrees by a purpose built goniometer. Radiographs were 2, irregularities on the surface or basal layer and loss of
then assessed for individual features of radiographic osteo- thickness of ,50%; grade 3, deep ulceration with loss of
arthritis (ROA) using the Altman atlas,24 as previously thickness of .50%; grade 4, full thickness chondral wear
described.19 with exposure of subchondral bone. A cartilage defect also
had to be present in at least two consecutive slices. The
Knee cartilage volume and thickness measurement cartilage defects were regraded 1 month later and the average
An MRI scan of the right knee was performed. Knee cartilage scores of cartilage defects in medial tibiofemoral (0–8), lateral
volume and thickness for tibial and patella plates and tibial tibiofemoral (0–8), patellar (0–4), and whole compartments
and patella bone size were determined, as previously (0–20) were used in the study. A prevalent cartilage defect
described.17–19 Femoral cartilage volume was not assessed as was defined as a cartilage defect score of >2 at any site
we have previously reported that two tibial sites and the within that compartment. Intraobserver reliability was 0.89–
patella site correlate strongly with this site.25 Medial and 0.94 and interobserver reliability was 0.85–0.93.

Table 2 Difference in knee cartilage and bone variables between subjects aged under
and over 45 years
Age ,45 years Age >45 years
(n = 167) (n = 205) p Value

Patellar cartilage defect (%) 16 38 ,0.001*

Medial tibiofemoral cartilage defect (%) 9 23 ,0.001*
Lateral tibiofemoral cartilage defect (%) 13 22 0.022*
Any cartilage defect (%) 31 54 ,0.001*
Patellar cartilage defect scores (0–4) 0.9 (0.8) 1.5 (1.1) ,0.001
Medial tibiofemoral cartilage defect scores (0–8) 2.0 (0.6) 2.2 (0.9) 0.003
Lateral tibiofemoral cartilage defect scores (0–8) 1.9 (0.6) 2.2 (0.8) 0.003
Total cartilage defect scores (0–20) 4.8 (1.5) 5.9 (2.0) ,0.001
Patellar cartilage volume (ml) 3.6 (0.9) 3.4 (1.0) 0.055
Medial cartilage volume (ml) 2.3 (0.5) 2.3 (0.6) 0.641
Lateral cartilage volume (ml) 2.6 (0.6) 2.6 (0.7) 0.789
Patellar cartilage thickness (mm) 5.5 (1.0) 5.0 (1.0) ,0.001
Medial cartilage thickness (mm) 3.8 (0.7) 3.6 (0.7) 0.003
Lateral cartilage thickness (mm) 4.6 (0.9) 4.4 (0.9) 0.010
Patellar bone volume (ml) 13.6 (3.3) 13.9 (3.3) 0.282
Medial tibial bone area (cm2) 17.3 (2.7) 17.5 (2.8) 0.666
Lateral tibial bone area (cm2) 11.7 (1.7) 12.2 (2.2) 0.024

Results are shown as mean (SD) except for cartilage defect prevalence.
*Determined by Mann-Whitney U test, all others by t test.

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Knee structure and age 551

Sex Sex Sex

F: r = +0.16, p = 0.018 F: r = +0.19, p = 0.005 F: r = +0.034, p < 0.001

M: r = +0.17, p = 0.03 M: r = +0.15, p = 0.07 M: r = +0.21, p = 0.008

T: r = +0.16, p = 0.002 T: r = +0.16, p = 0.002 T: r = +0.29, p < 0.001

A B C
8 7 5

7 6
Medial tibiofemoral defects

Lateral tibiofemoral defects

4
6
5

Patellar defects
5
3
4
4
3
2
3
2
2
1
1 1

0 0 0
20 30 40 50 60 70 20 30 40 50 60 70 20 30 40 50 60 70
Age (years) Age (years) Age (years)

Figure 1 Correlation between age and knee cartilage defects. There were significant positive associations between age and knee cartilage defect
score in the medial and lateral tibiofemoral and patellar compartments. T, total sample; F, female subjects; M, male subjects.

Statistics intermediate variable. All statistical analyses were performed

Correlation analysis was used to examine the association on SPSS version 10.0 for Windows (Chicago, IL).
between age and the various MRI measures. Linear regres-
sion analysis was then used to examine the associations after RESULTS
adjustment for age, sex, height, weight, offspring or control A total of 372 subjects (female 214, male 158) aged between
status, bone size, and/or ROA (total score). Cartilage defect 26 and 61 years (mean 45) took part. Table 1 presents the
scores in individual compartments were not normally demographic factors. The sex distribution, height, weight,
distributed but were for the combined total score. For past knee injury history, knee pain, and smoking were similar
comparability we used linear regression to assess age effects in subjects aged under and over the average age of 45 years,
for individual compartment and total score variables. Logistic but subjects aged over 45 years had greater body mass index
regression analysis was used to examine the associations and ROA prevalence.
between age and knee cartilage defect prevalence. A p value Age was associated with defect severity and prevalence in
,0.05 (two tailed) or a 95% confidence interval not including both categorical (table 2) and continuous analysis (fig 1,
the null point were regarded as significant. A 10% change in table 3). The positive associations remained after adjustment
the coefficient for age after adjustment for a variable was for sex, height, weight, and case-control status (all p,0.01)
accepted as providing evidence of a factor acting as an (table 3). The coefficients in the tibiofemoral and whole

Table 3 Associations between age and knee cartilage variables: multivariate analysis
Multivariate* Multivariate
Multivariate`

b (95% CI) (pa) b (95% CI) (pa) b (95% CI) (pa), % per decade

Patellar defect scores +0.040 (+0.026 to +0.054) +0.039 (+0.025 to +0.054) +0.039 (+0.024 to +0.053), +52%
Medial TBF defect scores +0.016 (+0.005 to +0.026) +0.012 (+0.001 to +0.022) +0.008 (20.002 to +0.018), +2.5%
Lateral TBF scores +0.017 (+0.006 to +0.028) +0.010 (20.001 to +0.021) +0.008 (20.003 to +0.019), +3.2%
Total defect scores +0.073 (+0.047 to +0.098) +0.058 (+0.032 to +0.084) +0.055 (+0.028 to +0.081), +8.7%
Patellar thickness (mm) 20.035 (20.048 to 20.021) 20.034 (20.048 to 20.020) 20.028 (20.042 to 20.015), 23.0%
Medial tibial thickness (mm) 20.013 (20.024 to 20.003) 20.014 (20.025 to 20.004) 20.011 (20.022 to 20.001), 22.2%
Lateral tibial thickness (mm) 20.019 (20.033 to 20.006) 20.017 (20.031 to 20.003) 20.014 (20.028 to 20.000), 22.4%
Patellar volume (ml) 211.5 (222.4 to 20.5) 214.8 (226.0 to 23.6) 210.0 (221.0 to +1.0), 21.5%
Medial tibial volume (ml) +4.5 (22.4 to +11.4) +1.4 (25.4 to +8.2) +3.5 (23.2 to +10.3), +1.2%
Lateral tibial volume (ml) 22.9 (210.1 to +4.3) 27.5 (214.9 to +0) 25.8 (213.2 to +1.5, 21.2%
Patellar bone volume (ml) +34.4 (+2.9 to +66.0) NA +27.6 (24.3 to +59.6), +1.5%
Medial tibial bone area (mm2) +3.0 (+0.7 to +5.4) NA +2.4 (+0.1 to +4.7), +1.3%
Lateral tibial bone area (mm2) +4.7 (+2.8 to +6.6) NA +4.0 (+2.2 to +5.7), +3.2%

Prevalent defects OR (95% CI) (pa) OR (95% CI) (pa) OR (95% CI) (pa)), % per decade
Patellar 1.10 (1.06 to 1.14) 1.10 (1.05 to 1.14) 1.07 (1.03 to 1.11), +12%
Medial tibiofemoral 1.08 (1.03 to 1.13) 1.06 (1.01 to 1.11) 1.05 (1.00 to 1.10), +4.5%
Lateral tibiofemoral 1.05 (1.01 to 1.09) 1.03 (0.99 to 1.08) 1.03 (0.98 to 1.08), +2.2%
Any 1.08 (1.04 to 1.11) 1.07 (1.03 to 1.11) 1.08 (1.04 to 1.11), +10%

Bold denotes statistically significant result.

*Adjusted for sex, height, weight, and case-control status;
adjusted for previous factors and bone size at that site; `further adjusted for ROA.
TBF, tibiofemoral; OR, odds ratio.

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552 Ding, Cicuttini, Scott, et al

Sex Sex Sex

F: r = –0.10, p = 0.163 F: r = –0.14, p = 0.039 F: r = –0.35, p < 0.001

M: r = –0.20, p = 0.014 M: r = –0.19, p = 0.015 M: r = –0.16, p = 0.045

T: r = –0.15, p = 0.004 T: r = –0.17, p = 0.001 T: r = –0.28, p < 0.001

A B C
7 8 8

Lateral tibial cartilage thickness (mm)

Medial tibial cartilage thickness (mm)

Patellar cartilage thickness (mm)

6 7 7

5 6 6

4 5 5

3 4 4

2 3 3

1 2 2
20 30 40 50 60 70 20 30 40 50 60 70 20 30 40 50 60 70
Age (years) Age (years) Age (years)

Figure 2 Correlation between age and knee cartilage thickness. There were significant negative associations between age and knee cartilage
thickness at all three sites. T, total sample; F, female subjects; M, male subjects.

compartment decreased by 21–45% after further adjustment subjects without ROA, the associations between age and knee
for bone size at that site, and those in the medial and lateral cartilage defects were similar to those in whole sample (data
tibiofemoral compartments were further decreased by 20– not shown).
33% after further adjustment for ROA and did not remain Subjects aged .45 years had lower knee cartilage thick-
statistically significant (table 3). Age was also significantly ness than those aged ,45 years at all sites (table 2). Age was
positively associated with prevalent knee cartilage defects in negatively associated with knee cartilage thickness at all
all compartments (OR = 1.05–1.10/year, all p,0.05) and three sites (all p,0.01; fig 2), and these negative associations
these associations changed little after adjustment for other remained significant after adjustment for sex, height, weight,
factors (table 3). When men and women were analysed case-control status, bone size at that site, and ROA in the
separately, age was significantly positively associated with total sample (all p,0.05; table 3). When men and women
severity (b = +0.014 to +0.083/year, all p,0.05) and pre- were analysed separately, age was significantly negatively
valence (OR = 1.08–1.13/year, all p,0.05) of knee cartilage associated with medial and lateral tibial cartilage thickness in
defects in all compartments in women, and with patellar men, and with patellar cartilage thickness in women in
(b = +0.027/year, p,0.01) and total (b = +0.056/year, multivariate analysis. Adjustment for bone size had little
p,0.01) defect severity in men in multivariate analysis. In effect on these associations, but the coefficients in women

Sex Sex Sex

F: r = –0.03, p = 0.67 F: r = –0.14, p = 0.039 F: r = –0.29, p < 0.001

M: r = +0.12, p = 0.14 M: r = +0.005, p = 0.95 M: r = +0.04, p = 0.60

T: r = +0.007, p = 0.89 T: r = –0.08, p = 0.11 T: r = –0.13, p = 0.01

A B C
5 6 7
Medial tibial cartilage volume (ml)

Lateral tibial cartilage volume (ml)

Patellar cartilage volume (ml)

4 6
5
4
5
4
3
4
3 3
3
2
2
2 3

1 1 1
20 30 40 50 60 70 20 30 40 50 60 70 20 30 40 50 60 70
Age (years) Age (years) Age (years)

Figure 3 Correlation between age and knee cartilage volume. There were significant negative correlations between age and patellar cartilage volume
in the total population and lateral cartilage volume in women only. T, total sample; F, female subjects; M, male subjects.

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Knee structure and age 553

Sex Sex Sex

F: r = +0.04, p = 0.54 F: r = +0.08, p = 0.24 F: r = +0.06, p = 0.42

M: r = +0.15, p = 0.07 M: r = +0.30, p < 0.001 M: r = +0.09, p = 0.27

T: r = +0.02, p = 0.65 T: r = +0.10, p = 0.058 T: r = +0.02, p = 0.76

A B C
30 30 30
Medial tibial bone area (cm2)

25

Patellar none volume (ml)

Lateral bone area (cm2)
25 25

20
20 20
15
15 15
10

10 10
5

5 5 0
20 30 40 50 60 70 20 30 40 50 60 70 20 30 40 50 60 70
Age (years) Age (years) Age (years)

Figure 4 Correlation between age and knee bone size. There were no significant positive associations between age and knee bone size except that at
the lateral tibial site in men. T, total sample; F, female subjects; M, male subjects.

decreased by 17–44% after adjustment for ROA (which was cartilage thinning and defects and bone enlargement are
predominantly joint space narrowing). the main processes that occur with aging.
There were non-significant differences in knee cartilage Knee cartilage defects assessed by MRI are highly
volume between those aged over and under 45 years at all comparable to arthroscopic13–15 and histological26 findings,
three sites (table 2). Age was negatively associated with and have been significantly associated with knee ROA27 28
patellar cartilage volume (p,0.001) and lateral tibial and pain.29 However, the association between knee cartilage
cartilage volume (p = 0.039) in women, but did not correlate defects and age has not previously been reported. In this
significantly with cartilage volume at other sites in women study we reported that age was positively associated with
and at all sites in men (fig 3). In multivariate analysis, age knee cartilage defect severity scores and prevalence in all
had no significant association with tibial cartilage volume but compartments, and these associations were stronger in
was negatively associated with patellar cartilage volume in women and at the patellar site. The prevalence of any knee
the total sample and women. The association decreased and cartilage defect was 54% in subjects after the average age of
became non-significant in the total sample after further 45 years, whereas the prevalence was 31% in subjects before
adjustment for ROA (table 3). the age of 45 years, suggesting that knee cartilage defects are
Those aged .45 years had higher lateral tibial bone area quite common in older subjects, even in those without ROA.
but not patellar bone volume and medial tibial bone area There is limited information on cartilage loss with age. A
than those aged ,45 years (table 2). Age had non-significant necropsy study has previously reported that patellar cartilage
positive correlations with knee bone size in correlation from women aged over 50 years showed progressive thinning
analysis (p.0.05), with the exception of lateral bone area with increasing age, which was less obvious in men.30
in men (p,0.01) (fig 4). However, in multivariate analysis, Radiographic studies have shown significant negative corre-
age was significantly positively associated with medial and lations between increasing age and joint space in both men
lateral tibial bone area and patellar bone volume in the total and women,9 10 whereas inconsistent associations are
sample. These associations decreased in magnitude but reported between joint space narrowing and age.9 12 The
remained significant for medial (p = 0.039) and lateral results from MRI studies have been inconsistent. Karvonen
(p,0.001) tibial bone area after further adjustment for et al reported that cartilage thickness decreased significantly
ROA score (table 3). When men and women were analysed at the femoral condylar, but not at tibial and patellar sites,31
separately, age was significantly associated with lateral tibial whereas Sargon et al reported that knee joint space declined
bone area in men, and with patellar bone volume and lateral linearly with increasing age.22 In an early study, Eckstein et al
tibial bone area in women. The association between age and suggested that knee cartilage volume and mean cartilage
medial tibial bone area in women was of borderline thickness were not associated with age, while patellar
maximal cartilage thickness was inversely associated with
significance (p = 0.07), and all the above associations
age.21 A subsequent larger study from Eckstein’s group
decreased in magnitude after adjustment for ROA.
reported a substantial decrease in thickness of cartilage in
the knee at all sites, although this did not reach statistical
DISCUSSION significance at the tibia.23 This is consistent with our results.
This cross sectional study documents associations between It is uncertain from the German study whether asymptomatic
age and knee cartilage defects, thickness, volume, and bone ROA was present as radiographs were not performed.
size in a convenience sample. In particular, the severity and Cicuttini et al reported that total and medial tibial cartilage
prevalence of knee cartilage defects and bone size increased, volumes, which were standardised for bone size (leading to
whereas knee cartilage thickness decreased with increasing an indirect measure of cartilage thickness), were inversely
age at all compartments or sites. While patellar cartilage associated with age in men consistent with our results, but
volume in women decreased with increasing age, tibial there was no significant association between age and lateral
cartilage volume remained unchanged, suggesting knee cartilage volume.20 These inconsistencies are probably due to

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554 Ding, Cicuttini, Scott, et al

variations in study samples—generally small sample size and which are met by this study.36 Secondly, measurement error
differing age and disease groups. may influence results. However, scoring of knee cartilage
In the current study we found that age was not defects, volume, thickness, and bone size measurement was
significantly associated with medial and lateral tibial highly reproducible, suggesting this is unlikely. Thirdly, ROA
cartilage volume either in men or women. This may reflect assessment allows us to examine whether the changes are of
the coexistence of cartilage hypertrophy and cartilage relevance to ROA. However, given the relative rarity and mild
thinning in early OA. However, tibial cartilage thickness severity of ROA in our sample, these results may not be
decreased significantly with age, and these decreases were generalisable to those with more severe OA. Fourthly, the
most obvious in men. In contrast, both patellar cartilage oldest subject in this sample was 61 years, and thus we
volume and thickness decreased with age, and these cannot comment on knee structural change after this age.
decreases were most obvious in women. These differences Lastly, we are unable to comment on meniscal pathology at
in volume changes at patellar and tibial sites may be real or the current time.
may reflect chance variation, and these results will need to be In conclusion, this cross sectional study suggests that the
replicated in other populations. most consistent knee structural changes with increasing age
Previous studies have suggested that knee joint surface are an increase in cartilage defect severity and prevalence,
area is not associated with age in 27 healthy men,21 whereas cartilage thinning, and an increase in bone size, with
the total cross sectional area of the tibial bone, assessed by inconsistent change in cartilage volume. Longitudinal studies
peripheral quantitative computed tomography, became pro- will be required to determine which of these changes are
gressively greater with age in 512 men and 693 women.32 primary and confirm their relevance to knee OA.
ROA was not assessed in this study so it is uncertain whether
this was mediated by osteophytes. In the current sample, we ACKNOWLEDGEMENTS
found that age was positively associated with patellar bone A special thanks to the subjects and orthopaedic surgeons who made
volume as well as lateral and medial tibial bone area after this study possible. The role of Sr C Boon in coordinating the study is
adjustment for sex, height, weight, and offspring or control gratefully acknowledged. We would like to thank Martin Rush who
status. The reasons for the age related increase in knee bone performed the MRI scans, Kevin Morris for technical support, and
Professor Dave Hosmer for statistical advice.
size are unknown, as most studies suggest that insulin-like
Supported by the National Health and Medical Research Council of
growth factor I and transforming growth factor b in bone Australia, Masonic Centenary Research Foundation.
decrease with age.33 34 The need to maintain adequate bone
mechanical competence in the face of declining bone density .....................
may be one reason for the increase in bone cross sectional Authors’ affiliations
area in aging men.32 These associations may be of direct C Ding, F Scott, H Cooley, G Jones, Menzies Research Institute,
relevance to OA when combined with our previous reports University of Tasmania, Hobart, Australia
that knee bone size is increased in subjects with early ROA19 F Cicuttini, Department of Epidemiology and Preventive Medicine,
and in the offspring of subjects at higher risk of OA.35 Monash University Medical School, Melbourne, Australia
The age related increase in knee bone size is a possible
explanation for age related knee cartilage alterations. In the REFERENCES
present study the associations between age and knee 1 Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM,
cartilage defect scores in tibiofemoral compartments Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T,
decreased in magnitude after adjustment for tibial bone Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA,
Brandt KD, Fries JF. Osteoarthritis: new insights. Part 1: the disease and its risk
area, but the associations between age, cartilage thickness, factors. Ann Intern Med 2000;133:635–46.
and patellar cartilage volume changed little after adjustment 2 Oliveria SA, Felson DT, Reed JI, Cirillo PA, Walker AM. Incidence of
for bone size, suggesting that age related increases in bone symptomatic hand, hip, and knee osteoarthritis among patients in a health
maintenance organization. Arthritis Rheum 1995;38:1134–41.
area are linked to tibiofemoral cartilage defects, but not 3 Kempson GE. Age-related changes in the tensile properties of human articular
cartilage thickness or volume. cartilage: a comparative study between the femoral head of the hip joint and
The relevance of these structural changes to OA remains the talus of the ankle joint. Biochim Biophys Acta 1991;31:223–30.
uncertain. The associations between age and knee cartilage 4 Bank RA, Bayliss MT, Lafeber FP, Maroudas A, Tekoppele JM. Ageing
and zonal variation in post-translational modification of collagen in
defect scores in tibiofemoral compartments became non- normal human articular cartilage: the age-related increase in non-enzymatic
significant after adjustment for ROA. The associations glycation affects biomechanical properties of cartilage. Biochem J
between age and cartilage thickness, patellar cartilage 1998;330:345–51.
5 Brandt KD, Fife RS. Ageing in relation to the pathogenesis of osteoarthritis.
volume, and knee bone size decreased in magnitude after Clin Rheum Dis 1986;12:117–30.
adjustment for ROA, suggesting that age related alteration in 6 Verzijl N, Bank RA, TeKoppele JM, DeGroot J. Ageing and osteoarthritis: a
all these factors is of direct relevance to tibiofemoral ROA. different perspective. Curr Opin Rheumatol 2003;15:616–22.
This was a cross sectional study and we cannot comment on 7 Mouritzen U, Christgau S, Lehmann HJ, Tanko LB, Christiansen C. Cartilage
turnover assessed with a newly developed assay measuring collagen type II
causal directions. Thus longitudinal data will be required to degradation products: influence of age, sex, menopause, hormone
determine which of these factors either singly or in replacement therapy, and body mass index. Ann Rheum Dis 2003;62:332–6.
combination is of most relevance to OA. In addition, we 8 Jordan JM, Luta G, Stabler T, Renner JB, Dragomir AD, Vilim V,
Hochberg MC, Helmick CG, Kraus VB. Ethnic and sex differences in serum
cannot comment on patellofemoral ROA, as these views are levels of cartilage oligomeric matrix protein: the Johnston County
not available. Osteoarthritis Project. Arthritis Rheum 2003;48:675–81.
This study has a number of other potential limitations. 9 Dacre JE, Scott DL, Da Silva JA, Welsh G, Huskisson EC. Joint space in
radiologically normal knees. Br J Rheumatol 1991;30:426–8.
Firstly, the study was primarily designed to look at genetic
10 Schouten JS, van den Ouweland FA, Valkenburg HA. A 12 year follow up
mechanisms of knee OA and used a matched design. The study in the general population on prognostic factors of cartilage loss in
matching was broken for the current study, but adjustment osteoarthritis of the knee. Ann Rheum Dis 1992;5:932–7.
for case-control status did not alter the results. Indeed, while 11 Hart DJ, Doyle DV, Spector TD. Incidence and risk factors for radiographic
knee osteoarthritis in middle-aged women: the Chingford Study. Arthritis
there was a reduction in power, the results otherwise did not Rheum 1999;42:17–24.
differ if examined in offspring and controls separately. 12 Lanyon P, O’Reilly S, Jones A, Doherty M. Radiographic assessment of
Although the sample is a convenience sample, Miettinen symptomatic knee osteoarthritis in the community: definitions and normal joint
space. Ann Rheum Dis 1998;57:595–601.
states that for these associations to be generalisable to other
13 Drape JL, Pessis E, Auleley GR, Chevrot A, Dougados M, Ayral X.
populations three key criteria need to be met in the selection, Quantitative MR imaging evaluation of chondropathy in osteoarthritic knees.
sample size, and adequate distribution of study factors, all of Radiology 1998;208:49–55.

www.annrheumdis.com
 Downloaded from http://ard.bmj.com/ on March 2, 2016 - Published by group.bmj.com
Knee structure and age 555

14 Pessis E, Drape JL, Ravaud P, Chevrot A, Dougados M, Ayral X. Assessment of 25 Cicuttini F, Wluka A, Stuckey S. Tibial and femoral cartilage changes in knee
progression in knee osteoarthritis: results of a 1 year study comparing osteoarthritis. Ann Rheum Dis 2001;60:977–980.
arthroscopy and MRI. Osteoarthritis Cartilage 2003;11:361–9. 26 McGibbon CA, Trahan CA. Measurement accuracy of focal cartilage defects
15 Potter HG, Linklater JM, Allen AA, Hannafin JA, Haas SB. Magnetic from MRI and correlation of MRI graded lesions with histology: a preliminary
resonance imaging of articular cartilage in the knee. An evaluation with use of study. Osteoarthritis Cartilage 2003;11:483–93.
fast-spin-echo imaging. J Bone Joint Surg Am 1998;80:1276–84. 27 Link TM, Steinbach LS, Ghosh S, Ries M, Lu Y, Lane N, Majumdar S.
16 Peterfy CG, van Dijke CF, Janzen DL, Gluer CC, Namba R, Majumdar S, Osteoarthritis: MR imaging findings in different stages of disease and
Lang P, Genant HK. Quantification of articular cartilage in the knee with correlation with clinical findings. Radiology 2003;226:373–81.
pulsed saturation transfer subtraction and fat-suppressed MR imaging: 28 Boegard T, Rudling O, Petersson IF, Jonsson K. Correlation between
optimization and validation. Radiology 1994;192:485–91. radiographically diagnosed osteophytes and magnetic resonance detected
17 Eckstein F, Schnier M, Haubner M, Priebsch J, Glaser C, Englmeier KH, cartilage defects in the tibiofemoral joint. Ann Rheum Dis 1998;57:401–7.
Reiser M. Accuracy of cartilage volume and thickness measurements with 29 Joensen AM, Hahn T, Gelineck J, Overvad K, Ingemann-Hansen T. Articular
magnetic resonance imaging. Clin Orthop 1998;352:137–48. cartilage lesions and anterior knee pain. Scand J Med Sci Sports
18 Jones G, Glisson M, Hynes K, Cicuttini F. Sex and site differences in cartilage 2001;11:115–9.
development: a possible explanation for variations in knee osteoarthritis in 30 Meachim G, Bentley G, Baker R. Effect of age on thickness of adult patellar
later life. Arthritis Rheum 2000;43:2543–8. articular cartilage. Ann Rheum Dis 1977;36:563–8.
31 Karvonen RL, Negendank WG, Teitge RA, Reed AH, Miller PR, Fernandez-
19 Jones G, Ding C, Scott F, Glisson M, Cicuttini F. Early radiographic
Madrid F. Factors affecting articular cartilage thickness in osteoarthritis and
osteoarthritis is associated with substantial changes in cartilage volume and
aging. J Rheumatol. 1994; 21, 1310–8.
tibial bone surface area in both males and females. Osteoarthritis Cartilage
32 Russo CR, Lauretani F, Bandinelli S, Bartali B, Di Iorio A, Volpato S,
2004;12:169–74.
Guralnik JM, Harris T, Ferrucci L. Aging bone in men and women: beyond
20 Cicuttini FM, Wluka A, Bailey M, O’Sullivan R, Poon C, Yeung S, Ebeling PR. changes in bone mineral density. Osteoporos Int 2003;14:531–8.
Factors affecting knee cartilage volume in healthy men. Rheumatology 33 Nicolas V, Prewett A, Bettica P, Mohan S, Finkelman RD, Baylink DJ, Farley JR.
2003;42:258–62. Age-related decreases in insulin-like growth factor-I and transforming growth
21 Eckstein F, Winzheimer M, Hohe J, Englmeier KH, Reiser M. Interindividual factor-beta in femoral cortical bone from both men and women: implications
variability and correlation among morphological parameters of knee joint for bone loss with aging. J Clin Endocrinol Metab 1994;78:1011–6.
cartilage plates: analysis with three-dimensional MR imaging. Osteoarthritis 34 Pfeilschifter J, Diel I, Scheppach B, Bretz A, Krempien R, Erdmann J,
Cartilage 2001;9:101–11. Schmid G, Reske N, Bismar H, Seck T, Krempien B, Ziegler R. Concentration of
22 Sargon MF, Taner D, Altintas K. Examination of joint space by magnetic transforming growth factor beta in human bone tissue: relationship to age,
resonance imaging in anatomically normal knees. Clin Anat 1996;9:386–90. menopause, bone turnover, and bone volume. J Bone Miner Res
23 Hudelmaier M, Glaser C, Hohe J, Englmeier KH, Reiser M, Putz R, Eckstein F. 1998;13:716–30.
Age-related changes in the morphology and deformational behavior of knee 35 Jones G, Ding C, Scott F, Cicuttini F. Genetic mechanisms of knee
joint cartilage. Arthritis Rheum 2001;44:2556–61. osteoarthritis: a population-based case control study. Ann Rheum Dis
24 Altman RD, Hochberg M, Murphy WA Jr, Wolfe F, Lequesne M. Atlas of 2004;63:1255–9.
individual radiographic features in osteoarthritis. Osteoarthritis Cartilage 36 Miettinen OS. Theoretical epidemiology: principles of occurrence research in
1995;3(suppl A):3–70. medicine. John Wiley and Sons, Inc, USA, 1985.

www.annrheumdis.com
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Association between age and knee structural

change: a cross sectional MRI based study
C Ding, F Cicuttini, F Scott, H Cooley and G Jones

Ann Rheum Dis 2005 64: 549-555

doi: 10.1136/ard.2004.023069

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