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Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes
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Research Article
Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes Felix Eckstein a,∗ , Heide Boeth b , Gerd Diederichs c , Wolfgang Wirth a , Martin Hudelmaier a , Sebastian Cotofana a , Margarethe Hofmann-Amtenbrink d , Georg Duda b a
Institute of Anatomy, Paracelsus Medical University, Salzburg, Austria Julius Wolff Institute, Charité – Universitätsmedizin Berlin, Center for Sports Science and Sports Medicine Berlin, Germany c Department of Radiology, Charité – Universitätsmedizin Berlin, Germany d Mat Search Consulting Hofmann, Pully, Switzerland b
a r t i c l e
i n f o
Article history: Received 22 October 2013 Received in revised form 8 November 2013 Accepted 10 November 2013 Available online xxx Keywords: Cartilage Thickness Subchondral bone Knee Development Adolescence Athletes
s u m m a r y Little is known about changes in human cartilage thickness and subchondral bone plate area (tAB) during growth. The objective of this study was to explore longitudinal change in femorotibial cartilage thickness and tAB in adolescent athletes, and to compare these data with those of mature former athletes. Twenty young (baseline age 16.0 ± 0.6 years) and 20 mature (46.3 ± 4.7 years) volleyball athletes were studied (10 men and 10 women in each group). Magnetic resonance images were acquired at baseline and at year 2-follow-up, and longitudinal changes in cartilage thickness and tAB were determined quantitatively after segmentation. The yearly increase in total femorotibial cartilage thickness was 0.8% (95% confidence interval [CI]: −0.5; 2.1%) in young men and 1.4% (95% CI: 0.7; 2.2%) in young women; the gain in tAB was 0.4% (95% CI: −0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%), respectively (no significant difference between sexes). The cartilage thickness increase was greatest in the medial femur, and was not significantly associated with the variability in tAB growth (r = −0.19). Mature athletes showed smaller gains in tAB, and lost >1% of femorotibial cartilage per annum, with the greatest loss observed in the lateral tibia. In conclusion, we find an increase in cartilage thickness (and some in tAB) in young athletes toward the end of adolescence. This increase appeared somewhat greater in women than men, but the differences between both sexes did not reach statistical significance. Mature (former) athletes displayed high rates of (lateral) femorotibial cartilage loss, potentially due to a high prevalence of knee injuries. © 2013 Elsevier GmbH. All rights reserved.
1. Introduction: The growth of the human skeleton has been investigated in great detail over many developmental phases, mainly using X-ray technology. Because X-rays are not capable of delineating soft tissues and cartilage, the growth and maturation in these articular tissues has instead been described in animal models (Hayes et al., 2001; Hunziker et al., 2007; Khan et al., 2007; Meller et al., 2009), and little is known about how human articular cartilage grows and forms in diarthrodial joints. With the advent of novel magnetic resonance imaging (MRI) sequences that can depict articular cartilage directly (Eckstein et al., 2001, 2006b; Peterfy et al., 1994) and
∗ Corresponding author at: Institute of Anatomy, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria. Tel.: +43 662 44 2002 1240; fax: +43 662 44 2002 1249. E-mail address: [email protected] (F. Eckstein).
ultrasound, few studies have quantitatively assessed cartilage in children or adolescents (Jones et al., 2000; Spannow et al., 2010), and only one study has generated longitudinal data on cartilage growth (Jones et al., 2003). In this study, the patellar and tibial (medial and lateral) cartilage volume was measured in 74 male and female Australian children, aged 9–18 years, approximately 1.5 years apart (range 1.3–1.9). The authors (Jones et al., 2003) reported a significant increase in articular cartilage volume, peaking in Tanner stage two, which is approximately at age 10–13 (a stage that is defined by the breast buds forming and the areola beginning to widen in young women, and by a testicular volume of 1.6–6 ml, the skin on the scrotum thinning and enlarging, and with the penis length still unchanged in young men). Further, this peak change appeared to be greater in young men than young women (Jones et al., 2003). The authors further reported that articular cartilage volume growth in the tibia (but not in the patella) correlated significantly with change in body height, and that – in terms of cartilage volume gain – overweight children did not differ significantly from
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Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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those with normal weight. Finally, tibial cartilage volume gain was greater in those who reported an average intensity of sport above the median (Jones et al., 2003). However, a limitation of the above study was its focus on “cartilage volume” as a morphometric outcome. Cartilage volume is determined (a) by the (mean) thickness of the cartilage and (b) by the size of the subchondral bone plate area, i.e. the area of the proximal or distal bone extremity (epiphysis) that is physiologically covered by articular cartilage (Buck et al., 2010). Therefore, it remains unclear whether the observed gain in cartilage volume during adolescence (Jones et al., 2003), and the observed sex differences thereof, were due to an increase in (mean) cartilage thickness, or due to growth of bone and subchondral bone plate area (Buck et al., 2010). Although the authors (Jones et al., 2003) performed caliper measurements of thickness at distinct locations, they were concerned that these may not be representative of the entire joint. Finally, the correlation seen between gain in cartilage volume and body height (Jones et al., 2003) may also be mediated by bone growth. The objective of the current study was therefore to answer the following questions: (a) Does the longitudinal change of knee cartilage thickness (and subchondral bone plate area) in adolescent athletes differ from that in mature athletes, who experienced a similar loading history (Carter and Wong, 1988) earlier in their lives and are still physically active? (b) Are there differences in longitudinal growth rates between male and female study participants? (c) Is there an (individual) association of cartilage thickness change with the growth of the subchondral bone plate areas? Such data are not only of theoretical interest: recently, great attention has been paid to measuring cartilage volume and thickness change after trauma, for instance after rupture of the anterior cruciate ligament (ACL) (Frobell et al., 2009; Frobell, 2011). Such measurements are useful, for instance, in evaluating the structural efficacy of surgical treatment (i.e. ACL repair) or other interventions, in an attempt to combat incident posttraumatic osteoarthritis (OA). ACL ruptures often occur in young athletes, and in the above studies (Frobell et al., 2009; Frobell, 2011) a longitudinal gain in cartilage volume and thickness was observed post-injury and was interpreted as a potential sign of (pathological) cartilage swelling. Therefore, longitudinal reference data in healthy adolescent athletes are needed, to be able to evaluate longitudinal changes in cartilage post-injury. 2. Material and methods 2.1. Study population We studied 40 top volleyball athletes: the adolescent group was at this time active at the Olympiastützpunkt (OSP) Berlin; they were aged 16.0 ± 0.6 years at baseline (10 male; 10 female) and trained twice per day for approximately 2 h (Table 1). Training was focused on strength, endurance, individual volleyball skills, and team playmaking strategies. Of the 10 boys, 2 had Osgood Schlatter disease, 1 had back pain, 2 had back pain as well as jumper’s knee, 1 had scoliosis, 1 had kidney issues, and 1 had had a medial meniscectomy in the knee contralateral to the one examined. Of the 10 girls, 1 had an ACL tear in the knee studied, 1 had an ACL and meniscus tear in the contralateral knee, 2 had knee pain (1 in combination with back pain), 1 had back pain and jumper’s knee 1 in combination with issues with the Achilles tendon, 2 had muscle pain, 1 had shoulder pain, and 1 had pain in both tibiae. The mature group consisted of former elite athletes, also from the OSP, who were on
Table 1 Demographic data of the study participants. Adolescent
No Age Height Weight BMI # With knee pain (CL) # ACL/Mx
Mature
Girls
Boys
Women
Men
10 15.7 ± 0.5 182 ± 4 70 ± 9 20.9 ± 2 2 (2) 1 (1)
10 16.3 ± 0.6 194 ± 5 84 ± 5 22.3 ± 0.9 2 (2) 0 (1)
10 46.6 ± 6 176 ± 5 71 ± 6 22.7 ± 1.9 2 (2) 3 (1)
10 46.1 ± 3 191 ± 5 95 ± 13 26 ± .6 2 4 (2) 3 (2)
ACL/Mx, ACL or meniscus surgery [usually meniscectomy] in the same knee (in the contralateral knee [CL]).
average 30 years older than the adolescent participants (46.3 ± 4.7 years; 10 men, 10 women, Table 1). All mature athletes were still currently playing volleyball at least twice a week. Of the 10 men, 3 had back pain (1 with a previous disk prolapse), 3 had back and knee pain (1 with lateral meniscectomy and 1 with other previous knee surgery), and 2 others had had meniscus surgery previously. Of the 10 women, 1 had a jumper’s knee and a previous Achilles tendon rupture, 3 had hip arthritis (1 with endoprosthetic surgery), 2 had knee pain (1 combined with back pain), 2 had had meniscus and 1 had had other surgery in the imaged knee, and 1 had had meniscus surgery in the contralateral knee. The study protocol was approved by the local ethics committee and all participants (and/or their parents) had signed informed consent to participate in the study. 2.2. Image acquisition using MRI Baseline and 2-year follow-up MR images of the dominant knee (the leg used for take-off) were acquired using a 1.5 T MRI scanner (Avanto, Siemens Medical Systems, Erlangen, Germany) and a dedicated 8-channel knee coil. To minimize the potential impact of the “daytime” on cartilage thickness (Sitoci et al., 2012), the images were always acquired in the morning (i.e. between 8 a.m. and 12 noon). All patients were positioned with the knee joint in the center of the coil, and with the leg almost in extension. A comprehensive set of MRI pulse sequences was acquired, with the sagittal 3D VIBE sequence with water excitation (1.5 mm slice thickness; 0.31 mm in-plane resolution, repetition time = 14.6 ms, echo time = 6.5 ms, flip angle = 20◦ ) used for cartilage quantification (Figs. 1 and 2). The follow-up acquisitions were made approx. 2 years after baseline imaging (24.3 ± 0.9 months; range 21–27), with all acquisition parameters being kept identical (Fig. 1). One adolescent girl had to be excluded due to limited image quality of the baseline data set, and one adolescent boy was excluded due to missing follow-up data. 2.3. Image segmentation and analysis The two knee image data sets per participant were processed with blinding to the time point of the acquisition (i.e. baseline and follow-up); a random time point was processed first, the other time point was processed second, using the first data set as a reference. The subchondral bone plate area (i.e. the interface between the cartilage and the subchondral bone) and the cartilage surface were segmented manually in each image showing the medial (MT) and lateral tibia (LT), and the weight-bearing (central) part of the medial (cMF) and/or the lateral femoral condyle (cLF) (Fig. 2). The weight-bearing aspect of the femoral condyles was separated from the posterior aspects using a 75% distance measure between the inter-condylar notch and the most posterior aspect of the condyles (Eckstein et al., 2009).
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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Fig. 1. Baseline and 2-year follow-up magnetic resonance images (sagittal 3D VIBE Water Excitation MRI Sequence) of an adolescent (top row) and of a mature volleyball athlete (bottom row).
Fig. 2. MR images showing cartilage thickness and subchondral bone area measurements acquired in the medial (top row) and in the lateral femorotibial compartment (bottom row), without segmentation on the left, and with segmentation of the cartilage surface (magenta line) and bone interface (green line) on the right. MFTC – medial femorotibial compartment; LFTC – lateral femorotibial compartment; MT – medial tibial condyle; cMF – central (weight-bearing) medial femoral condyle; LT – lateral tibial condyle; cLF – central (weight-bearing) lateral femoral condyle. (For interpretation of the references to color in this legend, the reader is referred to the web version of the article.)
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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The subchondral bone plate area (tAB) (Eckstein et al., 2006a) was determined by three-dimensional (3D) reconstruction (Hohe et al., 2002) of the bone interface segmentations (Fig. 2) in each of the 4 above regions of interests (MT, LT; cMF and cLF). The mean cartilage thickness over the tAB (ThCtAB) (Eckstein et al., 2006a) was computed in each cartilage plate, in 3D and independent of the original section orientation, using the bone interface and cartilage surface segmentations (Eckstein et al., 2006a; Stammberger et al., 1999). Medial femorotibial compartment (MFTC) values were derived as the sum of MT and cMF, lateral compartment (LFTC) values as the sum of LT and cLF (Eckstein et al., 2007). Total femorotibial joint (FTJ) values were computed as the sum of MFTC and LFTC. Cartilage volume was also determined for comparison with a previous report in Australian children (Jones et al., 2003). 2.4. Statistics Descriptive and conclusive statistical procedures were performed using SPSS 21 (IBM Corporation, NY). For each participant, we computed the absolute change between baseline and follow-up, and the relative (percent) change [(followup–baseline)/baseline × 100]. Because of subtle deviations of the follow-up period between participants, these changes were normalized to a 12-month observation period. The mean, standard deviation (SD) and 95% confidence intervals (CIs) of the changes were then computed based on individual annualized changes. Differences in the longitudinal changes between men and women were evaluated using an unpaired t-test; no correction for multiple testing between different regions of interest was performed, given the co-linearity in neighboring cartilage regions and in compartments vs. cartilage plates. Further, care was taken to interpret results as a whole, and not in isolation. The relationship between the changes in the subchondral bone plate area (tAB) and cartilage thickness (ThCtAB) was evaluated using Pearson correlation coefficients. 3. Results 3.1. Baseline descriptive findings on cartilage thickness and subchondral bone plate area At baseline, the tibial and femoral epiphyseal plates were still open in 5 adolescent women (Fig. 1), they were closed in 3, and 1 had borderline status; all had closed epiphyseal plates at follow-up. At baseline, the same numbers as for women applied to adolescent men, but 2 still had (marginally) open epiphyseal plates at followup. Baseline values of cartilage thickness and subchondral bone plate areas are presented in Table 2. Men displayed approximately 20% greater femorotibial cartilage thickness than women, both in adolescents and in mature participants. Adolescent men and women tended to have smaller cartilage thickness than mature participants in the medial femorotibial compartment, but greater thickness than mature adults in the lateral compartment (Table 2). Lateral compartment cartilage was thicker than medial compartment cartilage across all sex and age strata. Medially, the femoral cartilage was thicker compared to the tibial cartilage, while laterally, the tibial cartilage thickness was thicker compared to the medial cartilage; again, this was consistent across all sex and age strata (Table 2). These relationships are descriptive and have not been tested for statistical significance, as they did not pertain to the primary study questions. Men displayed approximately 28% greater femorotibial subchcondral bone areas than women, both in adolescents and in mature participants. No obvious differences were observed in the subchondral bone plate areas of adolescent and mature participants
Fig. 3. Percent [%] cartilage thickness change in adolescent volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. FTJ, total femorotibial joint; MT, medical tibial condyle; MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
(Table 2). Lateral compartment areas were generally larger than medial compartment areas (Table 2), but it should be noted that only the weight-bearing part of the femoral condyle (definition of ROI see above) was analyzed. 3.2. Longitudinal changes in cartilage thickness in adolescent and mature athletes In adolescent athletes, the yearly increase in total femorotibial (FTJ) cartilage thickness was 0.8% (95% confidence interval [CI]: −0.5; 2.1%) in young men, and 1.4% (95% CI: 0.7; 2.2%) in young women (Fig. 3). The percentage rates of cartilage thickening appeared to be greater in young women than men across all femorotibial regions; however, the differences between the sexes were not statistically significant (p > 0.25). The absolute changes (in m) across femorotibial regions are displayed in Table 3 and also did not differ significantly between men and women. The observed rates of cartilage accrual were greater medially, and were greatest in the weight-bearing medial femur, both in adolescent men and women (Fig. 3; Table 3). Mature athletes, in contrast, lost >1% (per annum) of cartilage in the FTJ, these rates were similar in men and women (Fig. 4), with the absolute change (m) being shown in Table 4. The observed rates of cartilage loss were greater laterally than medially (Fig. 4, Table 4). Laterally, they appeared to be greater in men than in
Fig. 4. Percent [%] cartilage thickness change in mature volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; FTJ, total femorotibial joint; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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Table 2 Adolescent and mature volleyball athletes: baseline values of femorotibial cartilage thickness and subchondral bone plate area in men and women. Region
Adolescent Men
Mature Women
Men
Women
Cartilage Thickness (ThCtAB) [mm]
FTJ MFTC LFTC MT cMF LT cLF
8.39 3.87 4.52 1.75 2.13 2.35 2.16
± ± ± ± ± ± ±
1.06 0.57 0.56 0.26 0.38 0.34 0.27
7.03 3.12 3.92 1.41 1.70 2.06 1.86
± ± ± ± ± ± ±
0.63 0.35 0.32 0.15 0.25 0.20 0.17
8.66 4.28 4.38 1.94 2.33 2.30 2.09
± ± ± ± ± ± ±
1.02 0.41 0.82 0.25 0.21 0.50 0.36
7.06 3.36 3.69 1.57 1.80 1.95 1.74
± ± ± ± ± ± ±
0.52 0.25 0.35 0.16 0.13 0.22 0.22
Subchondral bone area (tAB) [cm2 ]
FTJ MFTC LFTC MT cMF LT cLF
41.0 18.6 22.3 11.3 7.3 13.0 9.3
± ± ± ± ± ± ±
3.0 2.2 1.1 1.5 0.9 0.8 0.7
32.3 14.9 17.4 8.9 6.0 10.1 7.3
± ± ± ± ± ± ±
3.8 1.8 2.1 1.1 0.8 1.5 0.8
40.6 19.1 21.4 11.7 7.5 12.4 9.0
± ± ± ± ± ± ±
2.7 1.2 2.3 0.8 0.7 1.6 1.2
31.7 14.7 17.1 8.7 5.9 9.7 7.4
± ± ± ± ± ± ±
2.6 1.4 1.8 1.0 0.7 1.2 1.0
FTJ, total femorotibial joint [=MFTC + LFTC]; MFTC, medial femorotibial compartment [=MT + cMF]; LFTC, lateral femorotibial compartment [=LT + cLF]; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Table 3 Adolescent volleyball athletes: annualized longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in men and women. Region
Men
Women
p-Value
Mean
95% CI
Mean
95% CI
Cartilage thickness change (ThCtAB) [m]
FTJ MFTC LFTC MT cMF LT cLF
76 47 29 15 32 13 16
−39; 190 −17; 111 −25; 82 −15; 44 −7; 72 −19; 44 −8; 40
96 51 45 15 36 26 20
47; 146 21; 81 14; 77 −6; 35 21; 51 5; 46 0; 39
0.70 0.90 0.54 0.98 0.84 0.44 0.78
Subchondral bone area change (tAB) [mm2 ]
FTJ MFTC LFTC MT cMF LT cLF
16 5 11 2 3 6 5
−3; 34 −5; 16 0; 21 −6; 10 −2; 8 −2; 13 0; 10
22 9 13 4 5 6 7
7; 37 0; 18 6; 20 0; 8 −1; 12 4; 8 0; 14
0.56 0.52 0.69 0.66 0.53 0.95 0.60
p value is for unpaired t-test between men and women; FTJ, total femorotibial joint [=MFTC + LFTC]; MFTC, medial femorotibial compartment [=MT + cMF]; LFTC, lateral femorotibial compartment [=LT + cLF]; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Table 4 Mature volleyball athletes: annualized longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in men and women.
Cartilage thickness change (ThCtAB) [m]
Subchondral bone area change (tAB) [mm2 ]
Region
Men
Women
Mean
95% CI
FTJ MFTC LFTC MT cMF LT cLF FTJ MFTC LFTC MT cMF LT cLF
−103 −24 −79 −14 −10 −45 −34 10 5 5 1 4 5 0
−192; −14 −49; 1 −155; −3 −25; −3 −28; 9 −80; −10 −81; 13 −2; 22 −4; 14 −3; 12 −4; 6 −2; 10 0; 10 −9; 8
Mean −74 −30 −44 −24 −6 −23 −21 12 8 4 4 4 0 4
p-Value 95% CI −146; −2 −64; 4 −99; 11 −40; −7 −25; 12 −44; −2 −57; 15 3; 21 3; 13 −3; 11 1; 7 0; 8 −5; 5 0; 8
0.58 0.74 0.41 0.29 0.78 0.24 0.63 0.73 0.54 0.93 0.28 0.98 0.14 0.29
p value is for unpaired t-test between men and women; FTJ, total femorotibial joint [=MFTC + LFTC]; MFTC, medial femorotibial compartment [=MT + cMF]; LFTC, lateral femorotibial compartment [=LT + cLF]; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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Fig. 5. Percentage [%] change in subchondral bone plate area in adolescent volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; FTJ, total femorotibial joint, MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
women (particularly in the lateral tibia: −2.6% in men vs. −1.2% in women; Fig. 4; Table 4), but the difference did not reach statistical significance (p = 0.33). 3.3. Longitudinal changes in subchondral bone plate area in adolescent and mature athletes In adolescent athletes, the yearly increase in total femorotibial (FTJ) subchondral bone plate area was 0.4% (95% CI: −0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%) in young women (Fig. 5). The percentage rates of subchondral bone expansion appeared to be greater in young women than men across all femorotibial regions; however, the differences between both sexes were not statistically significant (p > 0.27). The absolute changes (in m) across femorotibial regions are displayed in Table 4, which also did not differ significantly between men and women. Rates of subchondral bone expansion appeared to be greater in the weight-bearing femora than in the tibiae (Fig. 5, Table 4). The variability in rates of cartilage thickness gain across adolescent women and men was not significantly associated with the variability in the increase of subchondral bone plate area and correlation coefficients varied between r = −0.19 (medial femur) and +0.33 (lateral tibia). Mature athletes generally showed lower rates of subchondral bone expansion than adolescents, with the medial femur being the only region showing a consistent increase (approximately 0.6% in both men and women) (Fig. 6; Table 4). 4. Discussion To our knowledge, this is the first study to report the longitudinal rate of cartilage thickness change in (athletic) adolescents, and to compare these to mature adults with a similar history of athletic activity. We find an increase in cartilage thickness (and some also in subchondral bone plate area) in young athletes toward the end of adolescence; this increase appeared somewhat greater in women than men, but the differences did not reach statistical significance. The increase in cartilage thickness was strongest in the medial femur, and was not associated with the (individual) growth of the subchondral bone plate area. Mature (former) athletes, in contrast, showed cartilage loss, which was greatest in the lateral femorotibial compartment. This study has several limitations: the number of participants was limited and we may therefore have had limited power to
Fig. 6. Percentage [%] change in subchondral bone plate area in mature volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; FTJ, total femorotibial joint, MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
detect significant differences in cartilage accrual rates between men and women. Only one (relatively well defined) period around the end of adolescence was studied (and one approximately 30 years later), but preferably one would like to study the dynamics of cartilage thickness throughout the entire spectrum of developmental, adult, and senile stages. Thirdly, the participants were very active, athletic and had knee-related comorbidities (in particularly the mature group), and the study lacks a reference group of less physically active adults without knee injuries. Physical activity has been shown to be related to cartilage volume accrual in children (Jones et al., 2003), and subchondral bone plate areas (but not cartilage thickness) were found to be greater in adult triathletes compared with non-athletic controls (Eckstein et al., 2002). One young female athlete in our cohort had an ACL tear, but the longitudinal rates observed in her knee were well within the 95% confidence limits of the other participants. Due to the small sample size and heterogeneity of the pathology, we did not make an attempt to stratify the mature adults into those with and without knee-related comorbidity. Only one previous study reported longitudinal changes in male and female children (aged 9–18 years) and focused on cartilage volume (Jones et al., 2003). Yet, an increase in cartilage volume may be observed with an increase in cartilage thickness, or lateral expansion of the subchondral bone plate and overlying cartilage, or both, but is not specific to either process (Buck et al., 2010). The authors reported a peak in cartilage volume gain at Tanner stage 2 (approximately age 10–13). They observed an increase of 350 L/year in the medial and 256 L/year in the lateral tibia, whereas we observed much smaller increases of 19.5 mm3 (L) in the medial and 38.3 mm3 in the lateral tibia. This may be due to the volleyball athletes being at a later age spectrum of the cohort examined by Jones et al., and to cartilage volume accrual being greater at an earlier age (Jones et al., 2003). The authors also reported that cartilage accrual was greater in young men than women (Jones et al., 2003), which contrasts with our findings of somewhat (albeit not significantly) greater increase in cartilage thickness and subchondral bone plate area in young women compared with men. Further, the authors (Jones et al., 2003) reported that volume growth in the tibial cartilage (but not in the patellar cartilage) correlated significantly with change in body height (Jones et al., 2003). We found no association between the rate of cartilage thickening and growth of subchondral bone plate area (i.e. metaphyseal expansion) in either female or male athletes, but did not measure body height change. The relationship described above (Jones et al., 2003)
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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may hence be due to an association between longitudinal (height change) and radial bone growth (increase in subchondral bone plate area and cartilage volume), but may not hold for an increase in cartilage thickness. Finally, single point caliper measurements by the above authors (Jones et al., 2003) indicated no increase in cartilage thickness (as opposed to volume) in the medial and a small loss of cartilage thickness in the lateral tibia, whereas our current measurements clearly confirm that cartilage thickness (and not only volume) increases during adolescence. The rates of medial femorotibial cartilage loss observed in the mature volleyball athletes was very similar to those observed in patients with moderate to advanced (Kellgren Lawrence grade [KLG] 3) knee osteoarthritis (OA) (Eckstein et al., 2011, 2012), i.e. 1.2% p.a., but those in the lateral compartment of the mature athletes (up to 2.5% in men) were much greater than those observed in KLG3 knee OA (<1% p.a.). In a healthy reference cohort without risk factors or knee OA and a mean age of 55 years, in contrast, no cartilage loss was observed in either the medial or lateral femorotibial compartment (Eckstein et al., 2011). The high rates of lateral cartilage loss may be due to the relatively high prevalence rates of traumatic injuries in the mature athletes. It has been shown previously that joint trauma (specifically ACL injury) involves bone marrow lesions and subchondral depression fractures, and that these are most frequently located in the (posterior) lateral tibia (Frobell et al., 2008). Despite the continued gain in cartilage thickness in the adolescents, their (baseline) cartilage thickness values were similar to those of mature athletes: this may be because the mature adults are already in a phase of cartilage loss, and it is currently unclear at what time a peak maximum cartilage thickness is reached during life. Cross sectional analysis of cartilage thickness in young adults after ACL injury indicated a 0.5 mm increase in medial compartment cartilage thickness between age 18 and 35 in men and women (Eckstein et al., 2013); however, longitudinal studies are required to precisely determine at which age peak cartilage thickness is attained. The baseline medial and lateral compartment values of the mature study participants were similar to those reported in subjects without radiographic knee OA aged 62 years, on average, in a population based study (i.e. the Framingham cohort), as well as to those in the above mentioned healthy reference cohort aged 55 years (Eckstein et al., 2010). Interestingly, in adolescents, the baseline cartilage thickness values in the medial compartment were somewhat less than in the mature participants, and relatively large rates of medial cartilage gain were (still) observed in adolescents. Lateral compartment baseline cartilage thickness values in the adolescents, in contrast, were (already) somewhat greater compared to those in the mature participants, and relatively large rates of lateral cartilage loss were observed in mature participants. These relationships were consistent between men and women. We found greater gains in cartilage thickness in the medial compartment (particularly in the medial femur) in late adolescence when compared to the lateral one, yet the exact cause of this distribution remains unclear. However, similar findings were observed in young mature subjects (18–35 years of age) following anterior cruciate ligament injury (Frobell et al., 2009; Frobell, 2011). As animal models of knee OA reported cartilage thickening (Calvo et al., 2001, 2004; Watson et al., 1996) or hypertrophy (Adams and Brandt, 1991; Vignon et al., 1983) as a response to mechanical challenges of the joint, the longitudinal gain in cartilage volume and thickness observed post-injury (Frobell et al., 2009; Frobell, 2011) was speculated to represent a pathological response following trauma and/or chronic alteration in joint mechanics. However, our current findings indicate that cartilage thickening may be physiological during adolescence and young adulthood, which is why we recommend that studies investigating cartilage change after trauma and/or ACL injury in
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adolescents or young adults should include an age-matched control cohort, or the contralateral knee for comparison. In conclusion, we find an increase in cartilage thickness (and some also in subchondral bone plate area) in young athletes toward the end of adolescence, this appeared somewhat greater in women than men; however, the difference between female and male athletes did not reach statistical significance. The increase in cartilage thickness was strongest in the medial femur, and was not positively associated with the (individual) growth of the subchondral bone plate area. In contrast, mature (former) athletes showed cartilage loss that predominated in the lateral compartment. Acknowledgment The research leading to these results has received funding from the European Community’s Seventh Framework Program2 (FP7 – NMP-2008-Large-2) under grant agreement No. 228929 (Nano Diara). Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.aanat. 2013.11.001. References Adams, M.E., Brandt, K.D., 1991. Hypertrophic repair of canine articular cartilage in osteoarthritis after anterior cruciate ligament transection. J. Rheumatol. 18, 428–435. Buck, R.J., Wyman, B.T., Le Graverand, M.P., Wirth, W., Eckstein, F., 2010. An efficient subset of morphological measures for articular cartilage in the healthy and diseased human knee. Magn. Reson. Med. 63, 680–690. Calvo, E., Palacios, I., Delgado, E., Ruiz-Cabello, J., Hernandez, P., Sanchez-Pernaute, O., Egido, J., Herrero-Beaumont, G., 2001. High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis. Osteoarthritis Cartilage 9, 463–472. Calvo, E., Palacios, I., Delgado, E., Sanchez-Pernaute, O., Largo, R., Egido, J., Herrero-Beaumont, G., 2004. Histopathological correlation of cartilage swelling detected by magnetic resonance imaging in early experimental osteoarthritis. Osteoarthritis Cartilage 12, 878–886. Carter, D.R., Wong, M., 1988. The role of mechanical loading histories in the development of diarthrodial joints. J. Orthop. Res. 6, 804–816. Eckstein, F., Ateshian, G., Burgkart, R., Burstein, D., Cicuttini, F., Dardzinski, B., Gray, M., Link, T.M., Majumdar, S., Mosher, T., Peterfy, C., Totterman, S., Waterton, J., Winalski, C.S., Felson, D., 2006a. Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis. Osteoarthritis Cartilage 14, 974–983. Eckstein, F., Benichou, O., Wirth, W., Nelson, D.R., Maschek, S., Hudelmaier, M., Kwoh, C.K., Guermazi, A., Hunter, D., 2009. Magnetic resonance imaging-based cartilage loss in painful contralateral knees with and without radiographic joint space narrowing: data from the osteoarthritis initiative. Arthritis Rheum. 61, 1218–1225. Eckstein, F., Faber, S., Muhlbauer, R., Hohe, J., Englmeier, K.H., Reiser, M., Putz, R., 2002. Functional adaptation of human joints to mechanical stimuli. Osteoarthritis Cartilage 10, 44–50. Eckstein, F., Hudelmaier, M., Putz, R., 2006b. The effects of exercise on human articular cartilage. J. Anat. 208, 491–512. Eckstein, F., Kunz, M., Hudelmaier, M., Jackson, R., Yu, J., Eaton, C.B., Schneider, E., 2007. Impact of coil design on the contrast-to-noise ratio, precision, and consistency of quantitative cartilage morphometry at 3 Tesla: a pilot study for the osteoarthritis initiative. Magn. Reson. Med. 57, 448–454. Eckstein, F., Nevitt, M., Gimona, A., Picha, K., Lee, J.H., Davies, R.Y., Dreher, D., Benichou, O., Le Graverand, M.P., Hudelmaier, M., Maschek, S., Wirth, W., 2011. Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the osteoarthritis initiative. Arthritis Care Res. (Hoboken.). 63, 311–319. Eckstein, F., Reiser, M., Englmeier, K.H., Putz, R., 2001. In vivo morphometry and functional analysis of human articular cartilage with quantitative magnetic resonance imaging – from image to data, from data to theory. Anat. Embryol. (Berl.) 203, 147–173. Eckstein, F., Wirth, W., Lohmander, S., Hudelmaier, M.I., Frobell, R., 2013. Age and sex-dependence of femorotibial cartilage change after anterior cruciate ligament (ACL) tear – 5 year follow-up in the KANON study. Osteoarthritis Cartilage 21 (Suppl.), S113 (Abstract).
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Research Article
Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes Felix Eckstein a,∗ , Heide Boeth b , Gerd Diederichs c , Wolfgang Wirth a , Martin Hudelmaier a , Sebastian Cotofana a , Margarethe Hofmann-Amtenbrink d , Georg Duda b a
Institute of Anatomy, Paracelsus Medical University, Salzburg, Austria Julius Wolff Institute, Charité – Universitätsmedizin Berlin, Center for Sports Science and Sports Medicine Berlin, Germany c Department of Radiology, Charité – Universitätsmedizin Berlin, Germany d Mat Search Consulting Hofmann, Pully, Switzerland b
a r t i c l e
i n f o
Article history: Received 22 October 2013 Received in revised form 8 November 2013 Accepted 10 November 2013 Available online xxx Keywords: Cartilage Thickness Subchondral bone Knee Development Adolescence Athletes
s u m m a r y Little is known about changes in human cartilage thickness and subchondral bone plate area (tAB) during growth. The objective of this study was to explore longitudinal change in femorotibial cartilage thickness and tAB in adolescent athletes, and to compare these data with those of mature former athletes. Twenty young (baseline age 16.0 ± 0.6 years) and 20 mature (46.3 ± 4.7 years) volleyball athletes were studied (10 men and 10 women in each group). Magnetic resonance images were acquired at baseline and at year 2-follow-up, and longitudinal changes in cartilage thickness and tAB were determined quantitatively after segmentation. The yearly increase in total femorotibial cartilage thickness was 0.8% (95% confidence interval [CI]: −0.5; 2.1%) in young men and 1.4% (95% CI: 0.7; 2.2%) in young women; the gain in tAB was 0.4% (95% CI: −0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%), respectively (no significant difference between sexes). The cartilage thickness increase was greatest in the medial femur, and was not significantly associated with the variability in tAB growth (r = −0.19). Mature athletes showed smaller gains in tAB, and lost >1% of femorotibial cartilage per annum, with the greatest loss observed in the lateral tibia. In conclusion, we find an increase in cartilage thickness (and some in tAB) in young athletes toward the end of adolescence. This increase appeared somewhat greater in women than men, but the differences between both sexes did not reach statistical significance. Mature (former) athletes displayed high rates of (lateral) femorotibial cartilage loss, potentially due to a high prevalence of knee injuries. © 2013 Elsevier GmbH. All rights reserved.
1. Introduction: The growth of the human skeleton has been investigated in great detail over many developmental phases, mainly using X-ray technology. Because X-rays are not capable of delineating soft tissues and cartilage, the growth and maturation in these articular tissues has instead been described in animal models (Hayes et al., 2001; Hunziker et al., 2007; Khan et al., 2007; Meller et al., 2009), and little is known about how human articular cartilage grows and forms in diarthrodial joints. With the advent of novel magnetic resonance imaging (MRI) sequences that can depict articular cartilage directly (Eckstein et al., 2001, 2006b; Peterfy et al., 1994) and
∗ Corresponding author at: Institute of Anatomy, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria. Tel.: +43 662 44 2002 1240; fax: +43 662 44 2002 1249. E-mail address: [email protected] (F. Eckstein).
ultrasound, few studies have quantitatively assessed cartilage in children or adolescents (Jones et al., 2000; Spannow et al., 2010), and only one study has generated longitudinal data on cartilage growth (Jones et al., 2003). In this study, the patellar and tibial (medial and lateral) cartilage volume was measured in 74 male and female Australian children, aged 9–18 years, approximately 1.5 years apart (range 1.3–1.9). The authors (Jones et al., 2003) reported a significant increase in articular cartilage volume, peaking in Tanner stage two, which is approximately at age 10–13 (a stage that is defined by the breast buds forming and the areola beginning to widen in young women, and by a testicular volume of 1.6–6 ml, the skin on the scrotum thinning and enlarging, and with the penis length still unchanged in young men). Further, this peak change appeared to be greater in young men than young women (Jones et al., 2003). The authors further reported that articular cartilage volume growth in the tibia (but not in the patella) correlated significantly with change in body height, and that – in terms of cartilage volume gain – overweight children did not differ significantly from
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those with normal weight. Finally, tibial cartilage volume gain was greater in those who reported an average intensity of sport above the median (Jones et al., 2003). However, a limitation of the above study was its focus on “cartilage volume” as a morphometric outcome. Cartilage volume is determined (a) by the (mean) thickness of the cartilage and (b) by the size of the subchondral bone plate area, i.e. the area of the proximal or distal bone extremity (epiphysis) that is physiologically covered by articular cartilage (Buck et al., 2010). Therefore, it remains unclear whether the observed gain in cartilage volume during adolescence (Jones et al., 2003), and the observed sex differences thereof, were due to an increase in (mean) cartilage thickness, or due to growth of bone and subchondral bone plate area (Buck et al., 2010). Although the authors (Jones et al., 2003) performed caliper measurements of thickness at distinct locations, they were concerned that these may not be representative of the entire joint. Finally, the correlation seen between gain in cartilage volume and body height (Jones et al., 2003) may also be mediated by bone growth. The objective of the current study was therefore to answer the following questions: (a) Does the longitudinal change of knee cartilage thickness (and subchondral bone plate area) in adolescent athletes differ from that in mature athletes, who experienced a similar loading history (Carter and Wong, 1988) earlier in their lives and are still physically active? (b) Are there differences in longitudinal growth rates between male and female study participants? (c) Is there an (individual) association of cartilage thickness change with the growth of the subchondral bone plate areas? Such data are not only of theoretical interest: recently, great attention has been paid to measuring cartilage volume and thickness change after trauma, for instance after rupture of the anterior cruciate ligament (ACL) (Frobell et al., 2009; Frobell, 2011). Such measurements are useful, for instance, in evaluating the structural efficacy of surgical treatment (i.e. ACL repair) or other interventions, in an attempt to combat incident posttraumatic osteoarthritis (OA). ACL ruptures often occur in young athletes, and in the above studies (Frobell et al., 2009; Frobell, 2011) a longitudinal gain in cartilage volume and thickness was observed post-injury and was interpreted as a potential sign of (pathological) cartilage swelling. Therefore, longitudinal reference data in healthy adolescent athletes are needed, to be able to evaluate longitudinal changes in cartilage post-injury. 2. Material and methods 2.1. Study population We studied 40 top volleyball athletes: the adolescent group was at this time active at the Olympiastützpunkt (OSP) Berlin; they were aged 16.0 ± 0.6 years at baseline (10 male; 10 female) and trained twice per day for approximately 2 h (Table 1). Training was focused on strength, endurance, individual volleyball skills, and team playmaking strategies. Of the 10 boys, 2 had Osgood Schlatter disease, 1 had back pain, 2 had back pain as well as jumper’s knee, 1 had scoliosis, 1 had kidney issues, and 1 had had a medial meniscectomy in the knee contralateral to the one examined. Of the 10 girls, 1 had an ACL tear in the knee studied, 1 had an ACL and meniscus tear in the contralateral knee, 2 had knee pain (1 in combination with back pain), 1 had back pain and jumper’s knee 1 in combination with issues with the Achilles tendon, 2 had muscle pain, 1 had shoulder pain, and 1 had pain in both tibiae. The mature group consisted of former elite athletes, also from the OSP, who were on
Table 1 Demographic data of the study participants. Adolescent
No Age Height Weight BMI # With knee pain (CL) # ACL/Mx
Mature
Girls
Boys
Women
Men
10 15.7 ± 0.5 182 ± 4 70 ± 9 20.9 ± 2 2 (2) 1 (1)
10 16.3 ± 0.6 194 ± 5 84 ± 5 22.3 ± 0.9 2 (2) 0 (1)
10 46.6 ± 6 176 ± 5 71 ± 6 22.7 ± 1.9 2 (2) 3 (1)
10 46.1 ± 3 191 ± 5 95 ± 13 26 ± .6 2 4 (2) 3 (2)
ACL/Mx, ACL or meniscus surgery [usually meniscectomy] in the same knee (in the contralateral knee [CL]).
average 30 years older than the adolescent participants (46.3 ± 4.7 years; 10 men, 10 women, Table 1). All mature athletes were still currently playing volleyball at least twice a week. Of the 10 men, 3 had back pain (1 with a previous disk prolapse), 3 had back and knee pain (1 with lateral meniscectomy and 1 with other previous knee surgery), and 2 others had had meniscus surgery previously. Of the 10 women, 1 had a jumper’s knee and a previous Achilles tendon rupture, 3 had hip arthritis (1 with endoprosthetic surgery), 2 had knee pain (1 combined with back pain), 2 had had meniscus and 1 had had other surgery in the imaged knee, and 1 had had meniscus surgery in the contralateral knee. The study protocol was approved by the local ethics committee and all participants (and/or their parents) had signed informed consent to participate in the study. 2.2. Image acquisition using MRI Baseline and 2-year follow-up MR images of the dominant knee (the leg used for take-off) were acquired using a 1.5 T MRI scanner (Avanto, Siemens Medical Systems, Erlangen, Germany) and a dedicated 8-channel knee coil. To minimize the potential impact of the “daytime” on cartilage thickness (Sitoci et al., 2012), the images were always acquired in the morning (i.e. between 8 a.m. and 12 noon). All patients were positioned with the knee joint in the center of the coil, and with the leg almost in extension. A comprehensive set of MRI pulse sequences was acquired, with the sagittal 3D VIBE sequence with water excitation (1.5 mm slice thickness; 0.31 mm in-plane resolution, repetition time = 14.6 ms, echo time = 6.5 ms, flip angle = 20◦ ) used for cartilage quantification (Figs. 1 and 2). The follow-up acquisitions were made approx. 2 years after baseline imaging (24.3 ± 0.9 months; range 21–27), with all acquisition parameters being kept identical (Fig. 1). One adolescent girl had to be excluded due to limited image quality of the baseline data set, and one adolescent boy was excluded due to missing follow-up data. 2.3. Image segmentation and analysis The two knee image data sets per participant were processed with blinding to the time point of the acquisition (i.e. baseline and follow-up); a random time point was processed first, the other time point was processed second, using the first data set as a reference. The subchondral bone plate area (i.e. the interface between the cartilage and the subchondral bone) and the cartilage surface were segmented manually in each image showing the medial (MT) and lateral tibia (LT), and the weight-bearing (central) part of the medial (cMF) and/or the lateral femoral condyle (cLF) (Fig. 2). The weight-bearing aspect of the femoral condyles was separated from the posterior aspects using a 75% distance measure between the inter-condylar notch and the most posterior aspect of the condyles (Eckstein et al., 2009).
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Fig. 1. Baseline and 2-year follow-up magnetic resonance images (sagittal 3D VIBE Water Excitation MRI Sequence) of an adolescent (top row) and of a mature volleyball athlete (bottom row).
Fig. 2. MR images showing cartilage thickness and subchondral bone area measurements acquired in the medial (top row) and in the lateral femorotibial compartment (bottom row), without segmentation on the left, and with segmentation of the cartilage surface (magenta line) and bone interface (green line) on the right. MFTC – medial femorotibial compartment; LFTC – lateral femorotibial compartment; MT – medial tibial condyle; cMF – central (weight-bearing) medial femoral condyle; LT – lateral tibial condyle; cLF – central (weight-bearing) lateral femoral condyle. (For interpretation of the references to color in this legend, the reader is referred to the web version of the article.)
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The subchondral bone plate area (tAB) (Eckstein et al., 2006a) was determined by three-dimensional (3D) reconstruction (Hohe et al., 2002) of the bone interface segmentations (Fig. 2) in each of the 4 above regions of interests (MT, LT; cMF and cLF). The mean cartilage thickness over the tAB (ThCtAB) (Eckstein et al., 2006a) was computed in each cartilage plate, in 3D and independent of the original section orientation, using the bone interface and cartilage surface segmentations (Eckstein et al., 2006a; Stammberger et al., 1999). Medial femorotibial compartment (MFTC) values were derived as the sum of MT and cMF, lateral compartment (LFTC) values as the sum of LT and cLF (Eckstein et al., 2007). Total femorotibial joint (FTJ) values were computed as the sum of MFTC and LFTC. Cartilage volume was also determined for comparison with a previous report in Australian children (Jones et al., 2003). 2.4. Statistics Descriptive and conclusive statistical procedures were performed using SPSS 21 (IBM Corporation, NY). For each participant, we computed the absolute change between baseline and follow-up, and the relative (percent) change [(followup–baseline)/baseline × 100]. Because of subtle deviations of the follow-up period between participants, these changes were normalized to a 12-month observation period. The mean, standard deviation (SD) and 95% confidence intervals (CIs) of the changes were then computed based on individual annualized changes. Differences in the longitudinal changes between men and women were evaluated using an unpaired t-test; no correction for multiple testing between different regions of interest was performed, given the co-linearity in neighboring cartilage regions and in compartments vs. cartilage plates. Further, care was taken to interpret results as a whole, and not in isolation. The relationship between the changes in the subchondral bone plate area (tAB) and cartilage thickness (ThCtAB) was evaluated using Pearson correlation coefficients. 3. Results 3.1. Baseline descriptive findings on cartilage thickness and subchondral bone plate area At baseline, the tibial and femoral epiphyseal plates were still open in 5 adolescent women (Fig. 1), they were closed in 3, and 1 had borderline status; all had closed epiphyseal plates at follow-up. At baseline, the same numbers as for women applied to adolescent men, but 2 still had (marginally) open epiphyseal plates at followup. Baseline values of cartilage thickness and subchondral bone plate areas are presented in Table 2. Men displayed approximately 20% greater femorotibial cartilage thickness than women, both in adolescents and in mature participants. Adolescent men and women tended to have smaller cartilage thickness than mature participants in the medial femorotibial compartment, but greater thickness than mature adults in the lateral compartment (Table 2). Lateral compartment cartilage was thicker than medial compartment cartilage across all sex and age strata. Medially, the femoral cartilage was thicker compared to the tibial cartilage, while laterally, the tibial cartilage thickness was thicker compared to the medial cartilage; again, this was consistent across all sex and age strata (Table 2). These relationships are descriptive and have not been tested for statistical significance, as they did not pertain to the primary study questions. Men displayed approximately 28% greater femorotibial subchcondral bone areas than women, both in adolescents and in mature participants. No obvious differences were observed in the subchondral bone plate areas of adolescent and mature participants
Fig. 3. Percent [%] cartilage thickness change in adolescent volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. FTJ, total femorotibial joint; MT, medical tibial condyle; MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
(Table 2). Lateral compartment areas were generally larger than medial compartment areas (Table 2), but it should be noted that only the weight-bearing part of the femoral condyle (definition of ROI see above) was analyzed. 3.2. Longitudinal changes in cartilage thickness in adolescent and mature athletes In adolescent athletes, the yearly increase in total femorotibial (FTJ) cartilage thickness was 0.8% (95% confidence interval [CI]: −0.5; 2.1%) in young men, and 1.4% (95% CI: 0.7; 2.2%) in young women (Fig. 3). The percentage rates of cartilage thickening appeared to be greater in young women than men across all femorotibial regions; however, the differences between the sexes were not statistically significant (p > 0.25). The absolute changes (in m) across femorotibial regions are displayed in Table 3 and also did not differ significantly between men and women. The observed rates of cartilage accrual were greater medially, and were greatest in the weight-bearing medial femur, both in adolescent men and women (Fig. 3; Table 3). Mature athletes, in contrast, lost >1% (per annum) of cartilage in the FTJ, these rates were similar in men and women (Fig. 4), with the absolute change (m) being shown in Table 4. The observed rates of cartilage loss were greater laterally than medially (Fig. 4, Table 4). Laterally, they appeared to be greater in men than in
Fig. 4. Percent [%] cartilage thickness change in mature volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; FTJ, total femorotibial joint; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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Table 2 Adolescent and mature volleyball athletes: baseline values of femorotibial cartilage thickness and subchondral bone plate area in men and women. Region
Adolescent Men
Mature Women
Men
Women
Cartilage Thickness (ThCtAB) [mm]
FTJ MFTC LFTC MT cMF LT cLF
8.39 3.87 4.52 1.75 2.13 2.35 2.16
± ± ± ± ± ± ±
1.06 0.57 0.56 0.26 0.38 0.34 0.27
7.03 3.12 3.92 1.41 1.70 2.06 1.86
± ± ± ± ± ± ±
0.63 0.35 0.32 0.15 0.25 0.20 0.17
8.66 4.28 4.38 1.94 2.33 2.30 2.09
± ± ± ± ± ± ±
1.02 0.41 0.82 0.25 0.21 0.50 0.36
7.06 3.36 3.69 1.57 1.80 1.95 1.74
± ± ± ± ± ± ±
0.52 0.25 0.35 0.16 0.13 0.22 0.22
Subchondral bone area (tAB) [cm2 ]
FTJ MFTC LFTC MT cMF LT cLF
41.0 18.6 22.3 11.3 7.3 13.0 9.3
± ± ± ± ± ± ±
3.0 2.2 1.1 1.5 0.9 0.8 0.7
32.3 14.9 17.4 8.9 6.0 10.1 7.3
± ± ± ± ± ± ±
3.8 1.8 2.1 1.1 0.8 1.5 0.8
40.6 19.1 21.4 11.7 7.5 12.4 9.0
± ± ± ± ± ± ±
2.7 1.2 2.3 0.8 0.7 1.6 1.2
31.7 14.7 17.1 8.7 5.9 9.7 7.4
± ± ± ± ± ± ±
2.6 1.4 1.8 1.0 0.7 1.2 1.0
FTJ, total femorotibial joint [=MFTC + LFTC]; MFTC, medial femorotibial compartment [=MT + cMF]; LFTC, lateral femorotibial compartment [=LT + cLF]; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Table 3 Adolescent volleyball athletes: annualized longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in men and women. Region
Men
Women
p-Value
Mean
95% CI
Mean
95% CI
Cartilage thickness change (ThCtAB) [m]
FTJ MFTC LFTC MT cMF LT cLF
76 47 29 15 32 13 16
−39; 190 −17; 111 −25; 82 −15; 44 −7; 72 −19; 44 −8; 40
96 51 45 15 36 26 20
47; 146 21; 81 14; 77 −6; 35 21; 51 5; 46 0; 39
0.70 0.90 0.54 0.98 0.84 0.44 0.78
Subchondral bone area change (tAB) [mm2 ]
FTJ MFTC LFTC MT cMF LT cLF
16 5 11 2 3 6 5
−3; 34 −5; 16 0; 21 −6; 10 −2; 8 −2; 13 0; 10
22 9 13 4 5 6 7
7; 37 0; 18 6; 20 0; 8 −1; 12 4; 8 0; 14
0.56 0.52 0.69 0.66 0.53 0.95 0.60
p value is for unpaired t-test between men and women; FTJ, total femorotibial joint [=MFTC + LFTC]; MFTC, medial femorotibial compartment [=MT + cMF]; LFTC, lateral femorotibial compartment [=LT + cLF]; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Table 4 Mature volleyball athletes: annualized longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in men and women.
Cartilage thickness change (ThCtAB) [m]
Subchondral bone area change (tAB) [mm2 ]
Region
Men
Women
Mean
95% CI
FTJ MFTC LFTC MT cMF LT cLF FTJ MFTC LFTC MT cMF LT cLF
−103 −24 −79 −14 −10 −45 −34 10 5 5 1 4 5 0
−192; −14 −49; 1 −155; −3 −25; −3 −28; 9 −80; −10 −81; 13 −2; 22 −4; 14 −3; 12 −4; 6 −2; 10 0; 10 −9; 8
Mean −74 −30 −44 −24 −6 −23 −21 12 8 4 4 4 0 4
p-Value 95% CI −146; −2 −64; 4 −99; 11 −40; −7 −25; 12 −44; −2 −57; 15 3; 21 3; 13 −3; 11 1; 7 0; 8 −5; 5 0; 8
0.58 0.74 0.41 0.29 0.78 0.24 0.63 0.73 0.54 0.93 0.28 0.98 0.14 0.29
p value is for unpaired t-test between men and women; FTJ, total femorotibial joint [=MFTC + LFTC]; MFTC, medial femorotibial compartment [=MT + cMF]; LFTC, lateral femorotibial compartment [=LT + cLF]; MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001
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Fig. 5. Percentage [%] change in subchondral bone plate area in adolescent volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; FTJ, total femorotibial joint, MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
women (particularly in the lateral tibia: −2.6% in men vs. −1.2% in women; Fig. 4; Table 4), but the difference did not reach statistical significance (p = 0.33). 3.3. Longitudinal changes in subchondral bone plate area in adolescent and mature athletes In adolescent athletes, the yearly increase in total femorotibial (FTJ) subchondral bone plate area was 0.4% (95% CI: −0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%) in young women (Fig. 5). The percentage rates of subchondral bone expansion appeared to be greater in young women than men across all femorotibial regions; however, the differences between both sexes were not statistically significant (p > 0.27). The absolute changes (in m) across femorotibial regions are displayed in Table 4, which also did not differ significantly between men and women. Rates of subchondral bone expansion appeared to be greater in the weight-bearing femora than in the tibiae (Fig. 5, Table 4). The variability in rates of cartilage thickness gain across adolescent women and men was not significantly associated with the variability in the increase of subchondral bone plate area and correlation coefficients varied between r = −0.19 (medial femur) and +0.33 (lateral tibia). Mature athletes generally showed lower rates of subchondral bone expansion than adolescents, with the medial femur being the only region showing a consistent increase (approximately 0.6% in both men and women) (Fig. 6; Table 4). 4. Discussion To our knowledge, this is the first study to report the longitudinal rate of cartilage thickness change in (athletic) adolescents, and to compare these to mature adults with a similar history of athletic activity. We find an increase in cartilage thickness (and some also in subchondral bone plate area) in young athletes toward the end of adolescence; this increase appeared somewhat greater in women than men, but the differences did not reach statistical significance. The increase in cartilage thickness was strongest in the medial femur, and was not associated with the (individual) growth of the subchondral bone plate area. Mature (former) athletes, in contrast, showed cartilage loss, which was greatest in the lateral femorotibial compartment. This study has several limitations: the number of participants was limited and we may therefore have had limited power to
Fig. 6. Percentage [%] change in subchondral bone plate area in mature volleyball athletes: bar graph showing the mean change and 95% confidence interval in men vs. women. MFTC, medial femorotibial compartment; LFTC, lateral femorotibial compartment; FTJ, total femorotibial joint, MT, medial tibial condyle; cMF, central (weight-bearing) medial femoral condyle; LT, lateral tibial condyle; cLF, central (weight-bearing) lateral femoral condyle.
detect significant differences in cartilage accrual rates between men and women. Only one (relatively well defined) period around the end of adolescence was studied (and one approximately 30 years later), but preferably one would like to study the dynamics of cartilage thickness throughout the entire spectrum of developmental, adult, and senile stages. Thirdly, the participants were very active, athletic and had knee-related comorbidities (in particularly the mature group), and the study lacks a reference group of less physically active adults without knee injuries. Physical activity has been shown to be related to cartilage volume accrual in children (Jones et al., 2003), and subchondral bone plate areas (but not cartilage thickness) were found to be greater in adult triathletes compared with non-athletic controls (Eckstein et al., 2002). One young female athlete in our cohort had an ACL tear, but the longitudinal rates observed in her knee were well within the 95% confidence limits of the other participants. Due to the small sample size and heterogeneity of the pathology, we did not make an attempt to stratify the mature adults into those with and without knee-related comorbidity. Only one previous study reported longitudinal changes in male and female children (aged 9–18 years) and focused on cartilage volume (Jones et al., 2003). Yet, an increase in cartilage volume may be observed with an increase in cartilage thickness, or lateral expansion of the subchondral bone plate and overlying cartilage, or both, but is not specific to either process (Buck et al., 2010). The authors reported a peak in cartilage volume gain at Tanner stage 2 (approximately age 10–13). They observed an increase of 350 L/year in the medial and 256 L/year in the lateral tibia, whereas we observed much smaller increases of 19.5 mm3 (L) in the medial and 38.3 mm3 in the lateral tibia. This may be due to the volleyball athletes being at a later age spectrum of the cohort examined by Jones et al., and to cartilage volume accrual being greater at an earlier age (Jones et al., 2003). The authors also reported that cartilage accrual was greater in young men than women (Jones et al., 2003), which contrasts with our findings of somewhat (albeit not significantly) greater increase in cartilage thickness and subchondral bone plate area in young women compared with men. Further, the authors (Jones et al., 2003) reported that volume growth in the tibial cartilage (but not in the patellar cartilage) correlated significantly with change in body height (Jones et al., 2003). We found no association between the rate of cartilage thickening and growth of subchondral bone plate area (i.e. metaphyseal expansion) in either female or male athletes, but did not measure body height change. The relationship described above (Jones et al., 2003)
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may hence be due to an association between longitudinal (height change) and radial bone growth (increase in subchondral bone plate area and cartilage volume), but may not hold for an increase in cartilage thickness. Finally, single point caliper measurements by the above authors (Jones et al., 2003) indicated no increase in cartilage thickness (as opposed to volume) in the medial and a small loss of cartilage thickness in the lateral tibia, whereas our current measurements clearly confirm that cartilage thickness (and not only volume) increases during adolescence. The rates of medial femorotibial cartilage loss observed in the mature volleyball athletes was very similar to those observed in patients with moderate to advanced (Kellgren Lawrence grade [KLG] 3) knee osteoarthritis (OA) (Eckstein et al., 2011, 2012), i.e. 1.2% p.a., but those in the lateral compartment of the mature athletes (up to 2.5% in men) were much greater than those observed in KLG3 knee OA (<1% p.a.). In a healthy reference cohort without risk factors or knee OA and a mean age of 55 years, in contrast, no cartilage loss was observed in either the medial or lateral femorotibial compartment (Eckstein et al., 2011). The high rates of lateral cartilage loss may be due to the relatively high prevalence rates of traumatic injuries in the mature athletes. It has been shown previously that joint trauma (specifically ACL injury) involves bone marrow lesions and subchondral depression fractures, and that these are most frequently located in the (posterior) lateral tibia (Frobell et al., 2008). Despite the continued gain in cartilage thickness in the adolescents, their (baseline) cartilage thickness values were similar to those of mature athletes: this may be because the mature adults are already in a phase of cartilage loss, and it is currently unclear at what time a peak maximum cartilage thickness is reached during life. Cross sectional analysis of cartilage thickness in young adults after ACL injury indicated a 0.5 mm increase in medial compartment cartilage thickness between age 18 and 35 in men and women (Eckstein et al., 2013); however, longitudinal studies are required to precisely determine at which age peak cartilage thickness is attained. The baseline medial and lateral compartment values of the mature study participants were similar to those reported in subjects without radiographic knee OA aged 62 years, on average, in a population based study (i.e. the Framingham cohort), as well as to those in the above mentioned healthy reference cohort aged 55 years (Eckstein et al., 2010). Interestingly, in adolescents, the baseline cartilage thickness values in the medial compartment were somewhat less than in the mature participants, and relatively large rates of medial cartilage gain were (still) observed in adolescents. Lateral compartment baseline cartilage thickness values in the adolescents, in contrast, were (already) somewhat greater compared to those in the mature participants, and relatively large rates of lateral cartilage loss were observed in mature participants. These relationships were consistent between men and women. We found greater gains in cartilage thickness in the medial compartment (particularly in the medial femur) in late adolescence when compared to the lateral one, yet the exact cause of this distribution remains unclear. However, similar findings were observed in young mature subjects (18–35 years of age) following anterior cruciate ligament injury (Frobell et al., 2009; Frobell, 2011). As animal models of knee OA reported cartilage thickening (Calvo et al., 2001, 2004; Watson et al., 1996) or hypertrophy (Adams and Brandt, 1991; Vignon et al., 1983) as a response to mechanical challenges of the joint, the longitudinal gain in cartilage volume and thickness observed post-injury (Frobell et al., 2009; Frobell, 2011) was speculated to represent a pathological response following trauma and/or chronic alteration in joint mechanics. However, our current findings indicate that cartilage thickening may be physiological during adolescence and young adulthood, which is why we recommend that studies investigating cartilage change after trauma and/or ACL injury in
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adolescents or young adults should include an age-matched control cohort, or the contralateral knee for comparison. In conclusion, we find an increase in cartilage thickness (and some also in subchondral bone plate area) in young athletes toward the end of adolescence, this appeared somewhat greater in women than men; however, the difference between female and male athletes did not reach statistical significance. The increase in cartilage thickness was strongest in the medial femur, and was not positively associated with the (individual) growth of the subchondral bone plate area. In contrast, mature (former) athletes showed cartilage loss that predominated in the lateral compartment. Acknowledgment The research leading to these results has received funding from the European Community’s Seventh Framework Program2 (FP7 – NMP-2008-Large-2) under grant agreement No. 228929 (Nano Diara). Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.aanat. 2013.11.001. References Adams, M.E., Brandt, K.D., 1991. Hypertrophic repair of canine articular cartilage in osteoarthritis after anterior cruciate ligament transection. J. Rheumatol. 18, 428–435. Buck, R.J., Wyman, B.T., Le Graverand, M.P., Wirth, W., Eckstein, F., 2010. An efficient subset of morphological measures for articular cartilage in the healthy and diseased human knee. Magn. Reson. Med. 63, 680–690. Calvo, E., Palacios, I., Delgado, E., Ruiz-Cabello, J., Hernandez, P., Sanchez-Pernaute, O., Egido, J., Herrero-Beaumont, G., 2001. High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis. Osteoarthritis Cartilage 9, 463–472. Calvo, E., Palacios, I., Delgado, E., Sanchez-Pernaute, O., Largo, R., Egido, J., Herrero-Beaumont, G., 2004. Histopathological correlation of cartilage swelling detected by magnetic resonance imaging in early experimental osteoarthritis. Osteoarthritis Cartilage 12, 878–886. Carter, D.R., Wong, M., 1988. The role of mechanical loading histories in the development of diarthrodial joints. J. Orthop. Res. 6, 804–816. Eckstein, F., Ateshian, G., Burgkart, R., Burstein, D., Cicuttini, F., Dardzinski, B., Gray, M., Link, T.M., Majumdar, S., Mosher, T., Peterfy, C., Totterman, S., Waterton, J., Winalski, C.S., Felson, D., 2006a. Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis. Osteoarthritis Cartilage 14, 974–983. Eckstein, F., Benichou, O., Wirth, W., Nelson, D.R., Maschek, S., Hudelmaier, M., Kwoh, C.K., Guermazi, A., Hunter, D., 2009. Magnetic resonance imaging-based cartilage loss in painful contralateral knees with and without radiographic joint space narrowing: data from the osteoarthritis initiative. Arthritis Rheum. 61, 1218–1225. Eckstein, F., Faber, S., Muhlbauer, R., Hohe, J., Englmeier, K.H., Reiser, M., Putz, R., 2002. Functional adaptation of human joints to mechanical stimuli. Osteoarthritis Cartilage 10, 44–50. Eckstein, F., Hudelmaier, M., Putz, R., 2006b. The effects of exercise on human articular cartilage. J. Anat. 208, 491–512. Eckstein, F., Kunz, M., Hudelmaier, M., Jackson, R., Yu, J., Eaton, C.B., Schneider, E., 2007. Impact of coil design on the contrast-to-noise ratio, precision, and consistency of quantitative cartilage morphometry at 3 Tesla: a pilot study for the osteoarthritis initiative. Magn. Reson. Med. 57, 448–454. Eckstein, F., Nevitt, M., Gimona, A., Picha, K., Lee, J.H., Davies, R.Y., Dreher, D., Benichou, O., Le Graverand, M.P., Hudelmaier, M., Maschek, S., Wirth, W., 2011. Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the osteoarthritis initiative. Arthritis Care Res. (Hoboken.). 63, 311–319. Eckstein, F., Reiser, M., Englmeier, K.H., Putz, R., 2001. In vivo morphometry and functional analysis of human articular cartilage with quantitative magnetic resonance imaging – from image to data, from data to theory. Anat. Embryol. (Berl.) 203, 147–173. Eckstein, F., Wirth, W., Lohmander, S., Hudelmaier, M.I., Frobell, R., 2013. Age and sex-dependence of femorotibial cartilage change after anterior cruciate ligament (ACL) tear – 5 year follow-up in the KANON study. Osteoarthritis Cartilage 21 (Suppl.), S113 (Abstract).
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Please cite this article in press as: Eckstein, F., et al., Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes. Ann. Anatomy (2014), http://dx.doi.org/10.1016/j.aanat.2013.11.001