Keywords cartilage - biomarkers - arthrosis - athletes
Introduction
The articular cartilage is a specialized avascular, aneural tissue that covers the
bony parts of the diarthrodial joints. Its function is to facilitate smooth motion
via its low frictional coefficient, in addition to absorbing shock and supporting
load in several planes.[1 ]
[2 ]
The preservation of the articular cartilage depends on maintaining the integrity of
its molecular structure.[1 ] The main macromolecules that comprise cartilage are collagen and proteoglycans;
during the course of life, the activity of the chondral cells is determined by several
autocrine and non-autocrine factors that result in the maintenance or destruction
of articular homeostasis. Osteoarthrosis is a common condition in the elderly, but
it can also affect young people who are subjected to excessive articular loads.[1 ]
[2 ]
[3 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ]
[13 ]
[14 ]
[15 ]
[16 ]
[17 ]
In adults, the activation of the articular function within the physiological limits
of load and work frequency is crucial to maintain joint health;[3 ]
[4 ]
[5 ]
[6 ]
[9 ]
[13 ] therefore, joints working below the required levels are also at risk of degenerating.[10 ]
Work frequency and articular overload are important factors in articular destruction,
which is characterized by damage to cartilaginous tissue.[2 ] Indeed, excessive exposure to overload leads to early articular wear,[2 ]
[3 ]
[4 ]
[5 ]
[6 ]
[9 ]
[10 ]
[13 ] which is then perpetuated by an inflammatory cascade that affects all of the articular
tissue.[16 ] Therefore, high-performance athletes subjected to excessive training loads over
a short period of time are at a higher risk of developing articular damage; the knees,
in particular, tend to be overexposed in most sports. As a function of the constant
demand for maximal performance, early articular wear and functional disabilities might
result in the end of an athletic career.
Most patients are diagnosed in the advanced stages of arthrosis, when a series of
metabolic events has already occurred, and the process is likely past the point at
which pharmacological and surgical interventions are truly effective.[18 ]
The products of collagen matrix degradation might serve as useful markers of the severity
and progression of arthrosis. Such products might be measured in the synovial fluid,
blood or urine, and thus supply important information for the early diagnosis of arthrosis.
Regarding Articular Collagen
Collagen represents 50 to 60% of the dry weight of the cartilage. Its fibers form
a dense network that gives shape to this tissue. The most important mechanical properties
of collagen are resistance and resilience, which are transmitted to the cartilage.[1 ]
Type-II collagen is specific to cartilage, and represents nearly 98% of the total
collagen content in this tissue.[1 ]
Type-II collagen is the largest macromolecule that composes the cartilage, and it
consists of three identical polypeptide chains arranged in a triple helix. Each such
chain is synthesized as a pro-chain that contains large pro-peptides at its ends,
which are separated from the central part by telopeptides. During the maturation of
type-II collagen molecules, proteases cleave the pro-peptides; thus, the mature structure
consists of the central part of the triple helix and telopeptides.
When the articular components degrade, they are expelled from their source tissue
and are measured most accurately in the articular fluid. However, when studying osteoarthritis,
the measurement of biomarkers in the blood and urine is made using less aggressive
methods that are still effective and precise.[1 ]
The carboxy-terminal telopeptide of type-II collagen (CTX-II) is a biomarker of articular
degradation. The use of CTX-II as a biomarker, in addition to its direct relationship
with the radiological grade of disease, clinical scores and severity of cartilaginous
lesions, is well established in the literature.[2 ]
[18 ]
[19 ]
[20 ]
[21 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]
[27 ]
[28 ] Thus, the measurement of CTX-II appears to be an effective method to investigate
the turnover of type-II collagen.
The present study aimed to detect the early degradation of articular type-II collagen
by measuring CTX-II levels in the blood of athletes performing different sports and
comparing them with those of a control group. We sought to establish whether sport
participation is a risk factor for early articular degradation in our country, and
which sport was the most harmful to articular type-II collagen in the investigated
population.
Materials and Methods
The present study was performed at the Sports Trauma Group of the Department of Orthopedics
and Traumatology of our institution. The study was approved by the institutional ethics
committee (number 244/11), and signed informed consent was obtained from every participant.
The study population consisted only of females aged between 18 and 25 years, who were
members of competitive sports teams, including soccer, futsal (a variant of association football played on a hard court), handball, volleyball
and swimming, at Clube Atlético São José, which is a partner of the Sports Trauma
Group of our institution. The participants had to have between 5 and 8 years of training
in the sport, and none of the athletes participated in other sports.
Patients with articular pain undergoing treatment, history of articular orthopedic
surgery or of untreated articular pain due to any cause were excluded from the study,
and all individuals in this group were female.
A total of 9 individuals with sedentary lifestyles who met the inclusion criteria
formed the control group. None of them had ever participated in sports in a competitive
way.
A total of 70 female participants aged between 18 and 25 years were included: soccer
(n = 15), futsal (n = 10), handball (n = 10), volleyball (n = 18) and swimming (n = 7); 9 individuals with sedentary lifestyles were included in the control group.
A total of 3 mL of blood was collected from each participant by simple venous puncture
of the non-dominant upper limb using a vacuum collection kit, in which there is contact
of the sample with ethylenediaminetetraacetic acid (EDTA), which does not affect the
result, and the body mass index (BMI) was calculated as the weight divided by the
height squared of each person.
The blood was centrifuged, and the plasma was stored at - 80∘C until all of the blood
samples were ready for analysis, in a total of 23 days, because the test was performed
in the same day. The samples were analyzed to detect human CTX-II using enzyme-linked
immunosorbent assays (ELISAs; Hu CTX-II kit, Cusabio Biotech, Houston, TX, US). This
test has 100% of specificity for human CTX-II without any cross-reactions, and a minimum
level of detection of 0.2 ng/mL, which is informed by the manufacturer.
The results were compared using the Student t -test with a 95% confidence interval (95%CI), and values of p < 0.05 were considered statistically significant.
Results
A total of 70 female participants aged between 18 and 25 years were included: soccer
(n = 15), futsal (n = 10), handball (n = 10), volleyball (n = 18) and swimming (n = 7); 9 individuals with sedentary lifestyles were included in the control group.
The average age for the control group was of 22.6 years, the mean BMI was of 22.3,
and the mean concentration of CTX-II was of 0.453 ng/mL ([Table 1 ]).
Table 1
Participant
Age (years)
Height (meters)
Weight (kilos)
BMI
CTX-II (ng/ml)
1
22
1.7
48
16.6
0.486
2
21
1.7
65
22.49
0.427
3
22
1.5
63
28
0.443
4
24
1.64
50
18.59
0.461
5
22
1.71
64
21.88
0.474
6
23
1.57
53
21.5
0.45
7
25
1.7
72
24.91
0.442
8
22
1.68
53
18.77
0.432
9
22
1.59
67
26.5
0.459
Among the 18 volleyball players, the average age was of 18.3 years, the mean BMI was
of 22.33, and the mean CTX-II was of 0.429 ng/mL; this team trained 36 hours per week
([Table 2 ]).
Table 2
Athlete
Age (years)
Height (meters)
Weight (kilos)
BMI
CTX-II (ng/ml)
10
18
1.85
80
23.37
0.421
11
18
1.71
74
25.3
0.418
12
18
1.79
66.6
20.78
0.426
13
19
1.8
70
21.6
0.424
14
19
1.83
75
22.39
0.637
15
20
1.86
66
19.07
0.449
16
20
1.82
67.5
20.37
0.443
17
18
1.66
54
19.59
0.407
18
18
1.77
66
21.06
0.615
19
19
1.86
75
21.67
0.451
20
23
1.73
83
27.73
0.509
21
18
1.79
86
26.84
0.506
22
18
1.62
52
19.81
0.577
23
18
1.79
70
21.84
0.591
24
18
1.82
71
21.43
0.434
25
18
1.86
80
23.12
0.418
26
18
1.75
68
22.2
0.429
27
18
1.62
61
23.24
0.429
Among the 15 soccer players, the average age was of 22.36 years, the mean BMI was
of 22.06, and the mean CTX-II was of 0.456 ng/mL; this team trained 15 hours per week
([Table 3 ]).
Table 3
Athlete
Age (years)
Height (meters)
Weight (kilos)
BMI
CTX-II (ng/ml)
28
25
1.61
52
20.06
0.526
29
24
1.67
74
26.53
0.498
30
18
1.75
60
19.59
0.466
31
21
1.62
59
22.48
0.499
32
19
1.68
56
17.84
0.527
33
20
1.56
52
21.37
0.495
34
25
1.68
70
24.8
0.476
35
24
1.57
57
23.12
0.475
36
22
1.63
62
23.33
0.496
37
22
1.6
57
22.26
0.46
38
24
1.54
50
21.08
0.441
39
25
1.7
67
23.18
0.431
40
19
1.65
65
23.87
0.136
41
19
1.76
60
19.36
0.136
42
21
1.62
62
23.33
0.507
Among the futsal players, the average age was of 18.5 years, the mean BMI was of 22.21, and the mean
CTX-II was of 0.542 ng/mL; this team trained 15 hours per week ([Table 4 ]).
Table 4
Athlete
Age (years)
Height (meters)
Weight (kilos)
BMI
CTX-II (ng/ml)
43
18
1.65
59
21.67
0.512
44
18
1.73
59
19.71
0.475
45
18
1.55
45
18.73
0.552
46
18
1.6
60
23.44
0.643
47
19
1.7
68
23.53
0.473
48
18
1.59
60
23.73
0.591
49
20
1.67
65
23.31
0.771
50
19
1.58
52
20.83
0.522
51
19
1.62
64
24.39
0.445
52
18
1.49
50
22.71
0.431
Among the handball players, the average age was of 18.9 years, the mean BMI was of
22.88, and the mean CTX-II was of 0.416 ng/mL; this team trained 25 hours per week
([Table 5 ]).
Table 5
Athlete
Age (years)
Height (meters)
Weight (kilos)
BMI
CTX-II (ng/ml)
53
19
1.61
56
21.6
0.419
54
18
1.71
71
24.28
0.439
55
18
1.75
69
22.53
0.451
56
18
1.67
48
17.21
0.41
57
21
1.69
83
29.06
0.522
58
19
1.68
69
24.44
0.297
59
18
1.6
55
21.48
0.471
60
19
1.82
72
21.73
0.332
61
21
1.7
65
22.49
0.358
62
18
1.71
70
23.93
0.458
Among the swimmers, the average age was of 18.9 years, the mean BMI was of 20.71,
and the mean CTX-II was of 0.373; this team trained 12 hours per week ([Table 6 ]).
Table 6
Athlete
Age (years)
Height (meters)
Weight (kilos)
BMI
CTX-II (ng/ml)
63
18
1.73
63
21.04
0.345
64
18
1.64
54
20.07
0.365
65
19
1.63
55
20.70
0.45
66
19
1.68
57
20.19
0.323
67
18
1.71
61
20.86
0.356
68
19
1.69
60
21
0.371
69
21
1.74
64
21.13
0.402
The following p -values were obtained by comparing the different sports to the control group using
the Student t -test: volleyball, p = 0.21 ([Fig. 1 ]); soccer, p = 0.91 ([Fig. 2 ]); handball, p = 0.13 ([Fig. 3 ]); futsal , p = 0.02 ([Fig. 4 ]); and swimming, p = 0.0015 ([Fig. 5 ]).
Fig. 1 Comparison between the CTX-II concentration results of the control group and of the
soccer players.
Fig. 2 Comparison between the CTX-II concentration results of the control group and of the
handball players.
Fig. 3 Comparison between the CTX-II concentration results of the control group and of the
volleyball players.
Fig. 4 Comparison between the CTX-II concentration results of the control group and of the
futsal players.
Fig. 5 Comparison between the CTX-II concentration results of the control group and of the
swimmers.
Thus, futsal represented the highest risk for type-II collagen degradation and consequently for
articular cartilage degradation, whereas swimming was a protective factor for the
articular cartilage in the investigated population.
Discussion
Currently, prevention is emphasized over treatment; thus, the early diagnosis of osteoarthrosis
is of paramount importance. In the case of athletes, early diagnosis is even more
important because their occupation depends directly on the health of their joints.
Because the first cleavage of articular type-II collagen catalyzed by collagenases
releases the CTX-II epitope, which can be measured in the blood, urine and synovial
fluid, it is a powerful tool for the early diagnosis of articular wear.
Type-II collagen is present in every synovial joint; however, the concentration of
CTX-II is higher in patients with knee and hip arthrosis compared with the overall
population.[27 ] CTX-II is a biomarker for cartilage destruction, and an increased level is a positive
predictor for articular space reduction.[27 ]
[28 ]
When we measured the concentration of CTX-II in athletes who play different sports,
we sought to detect whether the risk of overload and early articular destruction would
be higher for any particular sport. Although the sample size for each sport might
appear small, these are closed teams subjected to the same training load and, in theory,
to the same articular overload.
In our study population, the volleyball, handball and soccer players did not exhibit
higher type-II collagen degradation, although they participated intensively in high-impact
activities. Perhaps this finding is explained by the fact that the study population
was very young, and, for these three modalities, either the terrain or the shoes are
able to absorb the shock.
Type-II collagen degradation was highest among the futsal players, and was significantly different than that of the control group ([Fig. 4 ]) using a 95%CI. This discrepancy was likely because this sport is played on a rigid
floor, requires shoes that do not absorb shock, and has frequent shifts in direction
overload on the joints, especially the knees (repeated pivot movements).
Another remarkable finding is that the swimming team had significantly lower CTX-II
concentrations compared with the control group ([Fig. 5 ]). In other words, swimming was a protective factor for the articular collagen in
the investigated population. This finding is likely due to a combination of factors
known to protect the joints, including aerobic exercise, low-impact activity and strengthening
of the periarticular muscles.[17 ]
Conclusion
Therefore, we conclude that, in the investigated population, professional futsal training is a risk factor for type-II collagen degradation and, thus, for articular
cartilage degradation. In contrast, swimming is a protective factor for the joints
in this same population, resulting in less articular collagen degradation.
Such data suggests that some sports can indeed lead to early articular degradation.
Sports trauma physicians must consider this fact, and clinical protocols aimed at
joint protection must be studied and applied.
However, the findings of the present study indicate that some sports may provide joint
protection, suggesting an important tool to prevent joint erosion, and mixed training
may be highly beneficial for professional teams.
Further studies on this subject must be performed with larger samples, and they should
be aimed at controlling articular destruction using pharmacological and non-pharmacological
means.
In addition, the use of biomarkers of joint destruction is an important tool for the
early detection of joint overload. Those working in sports trauma need to diagnose
joint lesions early to improve the lives of athletes.
