Peculiarities of the process of bone modeling in children during the second growth sporting sport
Consideration of features of the structural and functional state of bone tissue in children during the second growth spurt based on the analysis of markers of bone modeling, the level of 25(OH)-D and indicators of ultrasound and X-ray densitometry.
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Kharkiv National Medical University
PECULIARITIES OF THE PROCESS OF BONE MODELING IN CHILDREN DURING THE SECOND GROWTH SPORTING SPORT
Osman N.S.
Introduction
bone second growth spurt
It is known that the growth process of the child is characterized by unevenness, when intensive growth is replaced by its slowdown. The period of intensive growth is accompanied by active processes of bone tissue modeling [1]. To ensure these processes requires a number of factors such as nutrition, age-appropriate exercise, environmental conditions and, of course, the genetic component [2, 3, 4, 5]. In addition to calcium, phosphorus, magnesium, which are directly involved in the formation of bone matrix, vitamin D plays an important role in bone metabolism [6, 7, 8, 9]. Studies conducted in different climatic and social characteristics show that the world's population is deficient or deficient in vitamin D. Thus, among children 1-15 years old living in Italy, a decrease in vitamin D levels is observed in 85% [10]. Mexico City examination of school-age children revealed 54% of children with vitamin D deficiency and 28% with vitamin D deficiency [11]. The child population of Norway has a deficiency of vitamin D in 22.0% of cases, and 38.3% - its deficiency, and only 39.7% of children have a sufficient level [12]. In Ukraine, vitamin D deficiency is 87.092%, children, its deficiency -10.0% of children, and normal values of only 3% of children [13, 14]. That is, the unsatisfactory supply of vitamin D does not depend on the geographical region and the level of solar radiation, so in the foreground is its adequate supply of food and additional intake of its dosage forms [15]. Maintaining optimal levels of vitamin D is one of the main factors in the adequate formation of the peak of bone tissue [16]. In addition to minerals and vitamin D, the protein component of bone tissue, namely the intercellular space, should be considered. Connective tissue also provides bone strength and the proper strength of bone tissue depends on the composition of proteinglycans, glycoproteins and collagen fibers. Adequate mineralization of bone tissue and optimal composition of the organic component in adolescents is the key to optimal structural and functional state of bone tissue in the future, which will be realized in reducing the number of low-energy fractures and, consequently - preserved quality of life in the elderly [17].
We aim to find features of the structural and functional state of bone tissue in children during the second growth spurt based on the analysis of markers of bone modeling, the level of 25(OH) -D and indicators of ultrasound and X-ray densitometry.
Presenting main material
We supervised 205 schoolchildren aged 9-17 living in Kharkiv, of which 112 (54.63%) were boys and 93 (45.37%) were girls. Criteria for inclusion in the study were: mature birth, compliance with the physical and neuropsychological development of the child's age, unencumbered family history (for diseases of the skeletal, endocrine systems, metabolic disorders, etc.); no intake of vitamin and mineral complexes, including vitamin D for 6 months before the examination. Exclusion criteria included: the presence of chronic somatic, endocrine and hereditary pathology.
The examined children were divided into three groups based on the presence and intensity of growth spurt. Group I included 50 children who had a growth spurt and for the current year gained in height from 8 to 12 cm; to group II - 46 children who had growth spurt and for the current year increased in height by more than 12 cm, to group III - 109 children who did not have growth spurt.
The survey included analysis of anamnesis data on specially developed individual child development cards, assessment of physical development according to WHO recommendations (Child Growth Standards, 2007), determination of body mass index, assessment of sexual development on the Tanner scale [18]. Assessment of the structural and functional state of bone tissue was performed using ultrasound (Sonost-2000, Korea) and dual-energy Xray absorptiometry (DXA) (HOLOGIC QDR W Explorer, USA) [19]. All children who took part in the study to screen for bone tissue underwent ultrasound densitometry on the heel bone. Thirty-two children with BMD were further treated with DXA (L1-L4 vertebral level).
Z-score < -2 was considered a criterion for reducing bone mineral density, according to the recommendations of The International Society For Clinical Densitometry (ISCD, 2019) [20].
The supply of vitamin D was determined by the level of its active metabolite 25(OH) -D in the blood by enzymelinked immunosorbent assay. The reference indicators were considered to be the data of the Guidelines for the treatment and prevention of vitamin D deficiency in the population of Central Europe: the recommended doses of vitamin D for a healthy population and at-risk groups (2013). Level 25(OH) -D less than 50 nmol / l was regarded as vitamin D deficiency, level 50-75 nmol / l - vitamin D deficiency, level 25(OH) -D 75-125 nmol / l was considered optimal [21].
To determine the status of biochemical markers of bone modeling, the levels of chondroitin sulfates and glycosaminoglycans in the blood and alkaline phosphatase were determined. Metabolism of glycosaminoglycans was studied by determining the amount of total hexosaminoglycan sulfates (GAG) in serum and their fractional composition by the method of MR Stern: I fraction - chondroitin-6-sulfate (GAGi), II - chondroitin-4-sulfate (GAGII) and III fraction - the sum of other highly sulfated hexosaminoglycans - keratan sulfates, heparan sulfates and dermatan sulfates (GAGiii). Alkaline phosphatase activity as one of the markers of osteoblast function was determined by kinetic colorimetric method.
The obtained data were statistically processed in Microsoft Office Excel 2007 and STATISTICA 7. Verification of the normality of the distribution of vitamin D levels and BMD values was performed using the Kolmogorov-Smirnov test using the Bolshevik correction (for groups 25 to 50 elements). The hypothesis of equality of the mean values of the obtained data corresponding to the normal distribution law was tested using the Student's test for independent samples. The null hypothesis was rejected at the confidence level of p < 0.05. To compare the relative indicators (percentage of cases of reduced BMD) used Fisher's test, which can be used when working with small samples, a confidence level of p < 0.05. Spearman's rank correlation coefficient (rs) was calculated to assess the relationship between BMD and vitamin D levels, polymorphic variants of the VDR gene. Data for the text are given as mean (M) and standard deviation (± o).
The survey was conducted after the written consent of the parents to the child's participation in the study and was performed in accordance with the principles of the Helsinki Declaration of Human Rights (1948) and the European Convention on Human Rights in Biomedicine (1997).
The analysis of the results of the assessment of children's physical development showed that 26 children (12.7%) of all respondents were at risk of developing overweight, 8 children (3.9%) were overweight. In children of all groups, sexual development corresponded to the age norm. Manifestations of undifferentiated connective tissue dysplasia were diagnosed in 133 children (64.8%), including 32 children (64.0%) of group I, 30 children (65.2%) of group II and 71 children (65.1%) of group III, i.e. a significant difference in the prevalence of undifferentiated connective tissue dysplasia in groups was not observed. Mitral valve prolapse was diagnosed in 30 children (14.6%), scoliotic posture in 50 children (24.4), flat feet in 86 children (41.9%), and abnormal left ventricular chord in 28 children (13, 6%), chest deformity - in 7 children (3.4%), kyphosis - in 8 children (3.9%). 46 children had two or more manifestations of connective tissue dysplasia.
Ultrasound densitometry revealed a decrease in bone mineral density in 24 children (48.0%) of group I (Z-score - 1.8 ± 0.56), 28 children (60.87%) of group II (Z-score) -1.96 ± 0.27) and in 43 children (39.45%) of group III (Z-score1.68 ± 0.72). Children with intensive growth spurt (p < 0.05) had significantly more frequent decrease in bone mineral density. After obtaining the written consent of the parents to conduct an additional DXA study, 32 children with low BMD values were examined. The results of the study showed that in 18 (56.25%) children BMD is reduced: in group I - 38.9%, in group II - 50.0% of cases. Thus, the frequency of decreased BMD in children of group II was significantly higher (p < 0.05) than in children of group I. The results of the assessment of the status of vitamin D in the examined children showed that in group I its deficiency has 41 children (82.0%), and its deficiency - 9 children (18.0%). The average level of 25(OH) -D in children in this group is 40.80 ± 9.44 nmol / l. In children of group II vitamin D deficiency was found in 40 children (86.96%), and its deficiency - in 6 (13.04%). The average level of 25(OH) -D in this group is 45.6 ± 5.14 nmol / l. In children of group III vitamin D deficiency was diagnosed in 91 children (83.5%), and its deficiency - in 18 (16.5%) children; the average level of 25(OH) -D in the group is 40.47 ± 9.49 nmol / l.
Thus, the results allow us to conclude that in children who do not have signs of second growth spurt, there is a dependence of BMD on the supply of vitamin D. In the group of children without growth spurt found a positive relationship between vitamin D and BMD (rs = 0.4).
This dependence was not detected in children with growth spurt, and in children with intensive growth spurt the absence of this dependence is more pronounced.
The average values of the level of 25(OH) -D in groups depending on the indicators of bone mineral density are shown in table 1.
Table 1
The average level of 25(OH) -D in children depending on the indicators of bone mineral density
BMD |
Group I Level 25- (OH)-D, nmol / l (M±g) |
Group II Level 25- (OH)-D, nmol / l (M±g) |
Group III Level 25- (OH)-D, nmol / l (M±g) |
|
Z- score >-2 |
42,43 ± 6,3 |
45,47 ± 4,69 |
42,91 ± 9,1 |
|
Z- score <-2 |
39,04 ± 11,84 |
45,68 ± 5,48 |
36,73 ± 8,94* |
* - positive correlation (rs = 0.4)
Analysis of the obtained indicators of markers of bone modeling showed that in children of groups I and II the level of total chondroitinsulfates was significantly higher (p < 0.05) than in children of group III (Table 2), which indicates instability of metabolic processes in connective tissue in children. However, there is no probable discrepancy between the average content of total chondroitinsulfates in children of groups I and II with low and normal bone mineral density, in contrast to the indicators of children in group III. These data are correlated with the results of the determination of fractional GAG. In children of group III, the content of total GAG significantly (p < 0.05) exceeds the corresponding figure of children of groups I and II. No significant difference between the content of total GAG in children of groups I and II was found, as well as no significant difference in groups I and II in children with normal BMD and low values. When studying the fractional composition of GAG, there was a significant (p < 0.05) increase in the level of chondroitin-6sulfate (GAGI) in children of group II, both with normal BMD and decreased BMD, which indicates instability of bone tissue modeling mechanisms in children during the second growth spurt. The content of chondroitin-4-sulfate (GAGII) and other highly sulfated hexosaminoglycans (GAGiii) was significantly (p < 0.05) lower in children of groups I and II in contrast to similar indicators in children of group III. The decrease in the content of these fractions indicates the intensity of bone modeling in children during the second growth spurt, which together with the increase in the level of GAGi in children of group II confirms the activity of bone processes in children with intensive growth spurt.
Table 2
Indicators of glycosaminoglycan metabolism in the serum of children depending on bone mineral density
Groups of children |
Chondroi tinsulfate s, g / l (M±c) |
GAG, un.,(M ±c) |
GAG fractions, units |
||||
І (M±c) |
ІІ (Mto) |
ІІІ (M±c) |
|||||
Group |
Zscore > -2 |
0,136 ± 0,049 |
9,86 ± 0,81 |
5,80 ± 0,26 |
2,98 ± 0,31 |
1,41 ± 0, 17 |
|
І |
Zscore < -2 |
0,142 ± 0,049 |
9,97 ± 1,12 |
6,54 ± 0,31 |
2,31 ± 0,17 |
1,23 ± 0, 23 |
|
Group |
Zscore > -2 |
0,137 ± 0,011 |
10,21 ± 0,67 |
6,91 ± 0,30 |
2,36 ± 0,26 |
1,34 ± 0, 21 |
|
ІІ |
Zscore < -2 |
0,139 ± 0,033 |
9,91 ± 0,57 |
6,87 ± 0,35 |
2,20 ± 0,20 |
1,09 ± 0, 19 |
|
Group |
Zscore > -2 |
0,064 ±0,017 |
12,13 ± 0,18 |
5,72 ± 0,11 |
3,71 ± 0,09 |
2,97 ± 0, 07 |
|
ІІІ |
Zscore < -2 |
0,110 ± 0,028 |
11,40 ± 0,89 |
6,36 ± 0,45 |
2,62 ± 0,24 |
2,47 ± 0, 04 |
Analysis of the processes of bone tissue modeling by the levels of the marker enzyme - alkaline phosphatase showed that in children with intensive growth spurt its content was significantly (p < 0.05) hig her than in children of groups I and III; there was no significant difference between alkaline phosphatase levels in children of group II with normal bone density and its reduction. In children of groups I and III, the level of alkaline phosphatase is significantly higher (p < 0.05) at low values of bone mineral density (table 3)
Table 3
The content of alkaline phosphatase in the blood of children, taking into account BMD
BMD |
Group I Alkaline phosphatase, U / l (M ± o) |
Group II Alkaline phosphatase, U / l (M ± o) |
Group III Alkaline phosphatase, U / l (M ± o) |
|
Zscore > -2 |
274,6 ± 149,9 |
384,9 ± 194,9 |
292,7 ± 180,5 |
|
Zscore <-2 |
340,2 ± 151,4* |
387,9 ± 147,9 |
350,6 ± 174,5* |
* - positive correlation
The correlation analysis showed that in groups I and III the relationship between alkaline phosphatase and BMD (rs = -0.27 and rs = -0.34) was found, which indicates the presence of metabolic changes that characterize the processes of bone resorption in children with low BMD. In children of group II, the relationship between these indicators was not detected (rs = 0.06), which confirms the pronounced activity of bone modeling in children during intensive growth, which in turn leads to the development of transient decrease in BMD, as evidenced by ultrasound and X-ray densitometry.
Conclusions
The prevalence of vitamin D deficiency and deficiency in school-age children is almost 100% and does not depend on the presence and intensity of the second growth spurt. In children during the second growth spurt there is a significantly higher decrease in bone mineral density, which depends on the intensity of growth spurt and does not depend on the status of vitamin D and is accompanied by changes in the protein component of bone tissue. Thus, during the second growth spurt in the development of bone mineralization disorders plays a role not only vitamin D deficiency, but also the activity of bone modeling processes and the body's ability to provide adequate levels of substances to build bone tissue.
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