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Журнал «Боль. Суставы. Позвоночник» Том 12, №4, 2022

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Мінеральна щільність кісткової тканини та інші фактори ризику в дітей та підлітків із низькоенергетичними переломами довгих кісток

Мінеральна щільність кісткової тканини та інші фактори ризику в дітей та підлітків із низькоенергетичними переломами довгих кісток

Авторы: F.Х. Umarov, Z.М. Matanov
State Institution “Republican Specialized Scientific and Practical Medical Center of Traumatology and Orthopedics of the Ministry of Health of the Republic of Uzbekistan”, Tashkent, Republic of Uzbekistan

Рубрики: Ревматология, Травматология и ортопедия

Разделы: Клинические исследования

Версия для печати


Резюме

Актуальність. Відзначається збільшення кількості дітей та підлітків зі зниженими віковими темпами накопичення кісткової маси, низьким рівнем мінеральної щільності кісткової тканини (МЩКТ) та переломами. Ця проблема широко висвітлюється в науковій літературі. Мета: оцінити показники МЩКТ у дітей та підлітків із низькоенергетичними переломами довгих кісток і рівень кальцію, фосфору, вітаміну D та лужної фосфатази в сироватці крові. Матеріали та методи. Досліджено індекс маси тіла, показники кісткової денситометрії, рівні вітаміну D, кальцію, фосфору та лужної фосфатази в сироватці крові 230 дітей та підлітків (173 хлопчики та 57 дівчаток) віком від 6 до 17 років, які знаходились на лікуванні з приводу переломів довгих кісток. Результати. Переломи відбувалися переважно в плечовій кістці (41,3 %) та кістках передпліччя (43 %). У 20 % дітей та підлітків із переломом спостерігалися відхилення від нормальних показників індексу маси тіла. Низькі показники МЩКТ у 86 з 230 обстежених виявлено в поперековому відділі хребта, лише в 66 (76,7 %) випадках порушення МЩКТ були наявні в проксимальному відділі стегнової кістки. При оцінці статусу вітаміну D показники були нормальними в 19,3 % дівчаток і 9,2 % хлопчиків. Виявлено зниження рівня кальцію та підвищення лужної фосфатази в сироватці крові. За показниками кореляції МЩКТ та вітаміну D у хлопчиків залежність ознак була статистично значущою в молодшому та старшому шкільному віці, у дівчаток — лише в молодшому шкільному. Установлено прямий зв’язок між низькими показниками МЩКТ та вітаміну D. Висновки. Низькі показники МЩКТ, вітаміну D, порушення фосфорно-кальцієвого обміну й ожиріння в дітей та підлітків можуть бути предикторами перелому.

Background. There are an increasing number of children and adolescents with reduced age-related rate of bone mass accumulation, low bone mineral density (BMD) and low-energy fractures. This problem is widely discussed in the scientific literature. Purpose of the study was to assess the BMD in children and adolescents with low-energy fractures of long bones and to investigate some biochemical parameters of bone metabolism. Materials and methods. Body mass index (BMI), bone densitometry, levels of vitamin D, calcium, phosphorus and alkaline phosphatase in blood serum of 230 children and adolescents with low-energy fractures of long bones, aged 6 to 17 years, who underwent treatment due to the fractures were studied. Results. Fractures occurred predominantly in 41.3 % of the humerus and 43 % of the forearm bones. 20 % of children and adolescents had abnormal BMI values. Low BMD values in 86 of 230 examinees were detected in the lumbar spine, of which only 66 (76.7 %) had BMD abnormalities in the hip. In assessing vitamin D status, 19.3 % of the girls and 9.2 % of the boys had normal vitamin D values. A decrease in calcium level and an increase in alkaline phosphatase in blood serum were found. In terms of BMD and vitamin D status, the dependence of boys was statistically significant in the elementary and high school groups, while in girls it was only in the elementary school group. A direct link between low BMD and vitamin D has been established. Conclusions. Low BMD, vitamin D, impaired calcium-phosphorus metabolism and obesity in children and adolescents may be considered predictors of fracture occurrence.


Ключевые слова

діти; підлітки; перелом; мінеральна щільність кісткової тканини; вітамін D; лабораторні показники

children; adolescents; fracture; bone mineral density; vitamin D; laboratory indices

doi: http://dx.doi.org/10.22141/pjs.12.4.2022.345

Introduction

Osteopenia and osteoporosis are multifactorial and highly prevalent. They are often asymptomatic in childhood and adolescence [1]. In the classification in children and adolescents there is primary and secondary osteoporosis [2, 3]. Primary osteoporosis is mainly due to genetic disorders. An exception in this group is juvenile idiopathic osteoporosis, a condition with unknown pathophysiology in which no genetic abnormalities are found, but the search for possible candidate genes is not excluded.
Secondary osteoporosis includes a large group of pathologies and can occur with reduced physical activity, impaired sexual development, malnutrition, low levels of vitamin D, calcium, magnesium, low body weight, the presence of somatic diseases, treatment with glucocorticoids and other drugs that interfere with bone metabolism.
There has been an increase in the number of children and adolescents with reduced age-related rates of bone mass accumulation, low bone mineral density (BMD) and low-energy fractures. The identification of risk factors for low BMD and osteoporosis in children and adolescents has been widely reported in the scientific literature [2, 4, 5]. 50 % of children and adolescents under 18 years of age have at least one fracture and 20 % have two or more fractures that occur with minimal trauma (low-intensity or low-energy trauma) [4]. To date, the area of research related to the development of osteoporosis in children is the most important and understudied in paediatric traumatology and entails orthopaedical problems.
With the introduction of modern bone densitometers into clinical practice, it is possible to diagnose BMD in children and adolescents with high accuracy, speed and safety. The International Society for Clinical Densitometry (ISCD) recommends that pediatric osteoporosis be defined by a combination of a Z-score ≤ –2 and the presence of a clinically significant fracture or long bone fracture and one or more vertebral compression fractures occurring without high-energy injury or with local disease regardless of BMD [6]. A precursor to osteoporosis may be low BMD, so early detection is important for prevention, initiation of treatment and specialized care [2].
Purpose of this study was to evaluate BMD in children and adolescents with low-energy fractures of long bones and to examine serum calcium, phosphorus, vitamin D and alkaline phosphatase.

Materials and methods

In the Clinic of Pediatric Traumatology of the Republican Specialized Scientific and Practical Medical Centre of Traumatology and Orthopedics of the Ministry of Health of the Republic of Uzbekistan, we studied the data of clinical, radiological and laboratory examination of 230 children and adolescents (173 boys and 57 girls) aged 6–17 years who were treated for low-energy fractures of long bones (Table 1).
In the clinic, the patients underwent diagnostic measures, including clinical, radiological examinations of the injured limbs, biochemical tests and bone densitometry. The inclusion criteria for children and adolescents in the study were: fracture of long bones, absence of somatic pathology and autoimmune diseases, and absence of physical deve–lopment disorders. Consent for bone densitometry and data processing was obtained from parents. The study was conducted in accordance with the ethical standards for examining children and adolescents with fractures, approved by the local committee on bioethics of State Institution “Republican Specialized Scientific and Practical Medical Center of Traumatology and Orthopedics of the Ministry of Health of the Republic of Uzbekistan”, protocol No. 12 dated December 4, 2019.
Bone densitometry. Bone mineral density was determined in 230 children and adolescents (57 girls and 173 boys) by dual-energy X-ray absorptiometry on a DMS STRATOS bone densitometer (France) using the Eurasian regulatory database. We used a pediatric program to assess the BMD of the lumbar spine (LS) (L1-L4, frontal projection) and the proximal femur (PF) (Dual Hip program). Examination of children and adolescents was performed on day 2–3 after surgical treatment. The level of mineralization was assessed by absolute BMD values using the Z-score at the studied skeletal levels, compared with the statistical average for healthy children and adolescents of the same age and sex. The diagnosis of osteoporosis was made by the presence of a fracture and low BMD (Z-score less than –2.0 and below), and attention was paid to children’s complaints of pain (pre-fracture condition) in the spine and extremities after vigorous physical activity. Low BMD (osteopenia) was assessed at a Z-score of –1 to –2.0, with no complaints or anamnesis evidence of bone pathology. According to the recommendations, the presence of low BMD in only one of the examined skeletal segments (LS or H) in children with a low-energy fracture is sufficient for the conclusion.
Body mass index assessment. Body mass index (BMI) was calculated according to the conventional formula: BMI = weight (kg)/height (m2). BMI status (normal, underweight, overweight, obese) was assessed on the basis of WHO standards for boys and girls of appropriate age [7].
Biochemical studies. Calcium (normal Ca: 2.2–2.55 mmol/l), phosphorus (normal P: 1.30–2.26 mmol/l) and alkaline phosphatase activity (normal ALP: 269–390 units/l) were determined in blood serum using electrolyte analyzer MINDRAY BS-330 (Japan) with standard reagent kits from the same company. The level of 25(OH)D 
was assessed by immunoluminescent analysis on a Roche HITACHI Cobas e 411 (Japan) using standard kits from the same company. Vitamin D status in children and adolescents was assessed according to recommendations: adequate level of supply: 30–50 ng/ml, insufficiency 21–29 ng/ml, deficiency 10–20 ng/ml, severe deficiency < 10 ng/ml [8].
Statistical processing of the data. A non-parametric method of assessing BMD was carried out using a four-field contingency table (comparison of percentages between two groups of children and adolescents), with significance of differences assessed by Chi-square to deter`mine the strength of association between the studied features. The Spearman rank correlation coefficient (non-parametric method) was used to identify and assess the relationship between BMD (g/cm2) (low values, osteoporosis) and vitamin D levels (ng/ml), i.e. between two series of quantitative indicators compared. The closeness of the relation between the cha–racteristics is assessed conventionally: values of the correlation rank < 0.3 — weak closeness of the relation; > 0.3 but < 0.7 — moderate closeness of the relation, and values of 0.7 and more — evidence of high closeness of the relation. If a greater (lesser) value of one indicator corresponds to a greater (lesser) value of another indicator, a direct correlation link can be concluded. Differences were considered statistically significant at p < 0.05.

Results

In children and adolescents aged 6–17 years, low-energy fractures (falling from one’s own height) of the humerus and forearm were the most common (41.3 and 43 %, respectively). In an examination of 230 children and adolescents with fracture, 184 (80 %) of them had normal BMI values and 46 (20 %) had abnormal BMI values. Of the 173 boys, 138 (79.8 %) had a normal BMI, 7 (4 %) had a BMI below normal, 19 (11 %) were overweight and 9 (5.2 %) were obese. Of the 57 girls, 46 (80.7 %) had normal BMI, 4 (7 %) were below normal, 5 (8.8 %) were overweight and 2 (3.5 %) were obese.
When examined on a bone densitometer, 86 (37.4 %) children and adolescents with long bone fractures showed low BMD. When comparing the indices of low LS and PF, there were inconsistencies. While 86 examinees had abnormalities in LS, only 66 (76.7 %) of them had abnormalities in PF, therefore, for further analysis we used Z-score of LS.
Children and adolescents with fractures were analyzed by groups: preschool age (6 years) — 25 children, junior school age (7–12 years) — 138 children, senior school age (13–17 years) — 67 children. The highest rate (60 %) of fractures was in junior school age children, lower in preschool age — 10.9 % and senior school age — 29.1 %. In each group in children and adolescents Z-score of the LS was analyzed for normal, low BMD, deviation from the reference norm, or osteoporosis (Table 2).
Statistically significant results were obtained when analyzing the presence of osteoporosis among girls of primary and high school age (χ2 was 23.37, p < 0.001). No statistically significant differences in the osteoporosis presence were revealed when comparing the indices of boys of primary and high school age as well as boys and girls of these age groups. Statistically significant differences were found for the pre–sence of low BMD between boys of primary and high school age (χ2 was 4.35, p < 0.04), as well as in girls of the same age groups (χ2 was 8.56, p < 0.004). Distinctive features were also revealed when comparing the preschool boys’ group with adolescents of middle school age (χ2 was 23.43, p < 0.001). Comparisons with the group of preschool age girls were not made, given the small number of children.
In the assessment of vitamin D levels, only 11 girls (19.3 %) out of 57 (Table 3) and 16 (9.2 %) boys out of 173 (Table 4) had normal vitamin D values. Boys had higher rates of vitamin D deficiency and insufficiency compared with girls. No statistically significant differences were found between the rates of vitamin D deficiency and insufficiency in the junior and senior school age groups in boys and girls.
A correlation analysis was performed between the BMD indices and vitamin D level. It was revealed that in girls of primary school age the dependence of signs was direct (low BMD indices related to low vitamin D level), statistically significant, (p < 0.05, Spearman correlation coefficient R was 0.34). No correlation of indices was detected in the high school girls’ group. In the correlation analysis for boys in the elementary school group, the correlation of the signs between BMD and vitamin D was statistically significant (R was 0.85, p = 0.000000) and in the high school group (R was 0.43, p = 0.0008). Analysis of BMD and vitamin D in preschool children showed that the dependence of the signs was statistically insignificant.
When serum calcium levels were assessed, 57.83 % of the boys and 68.4 % of the girls had reduced serum calcium levels in the blood serum after the fracture (Tables 5, 6). Phosphorus levels in the blood serum in 97.7 % of the boys and 94.7 % of the girls were within normal limits (Table 5). Alkaline phosphatase values in the blood serum were elevated in 93 % of the boys and 89.5 % of the girls.

Discussion

Osteoporosis has been described as a “pediatric disease with geriatric consequences” [9]. The period of childhood, from infancy to adolescence, is crucial for bone health because up to 90 % of bone mass is formed by the end of puberty [5]. Dual-energy X-ray absorptiometry is the preferred method for clinical measurement of BMD in children and adolescents because of its accessibility, reproducibility, speed, low ionizing radiation, and availability of a pediatric reference base.
In the scientific literature, the terms osteopenia, osteopenic syndrome, or low BMD are commonly used to describe BMD in children and adolescents to define a condition preceded by osteoporosis. The National Institute for Health and Clinical Excellence (ISCD) recommends using the term “low bone mineral density” in children and adolescents if the Z-score is –1 to –2 and osteoporosis if the Z-score is > –2.0, combined with impaired bone quality, increased bone fragility and fractures [10].
We determined the BMD in 230 children and adolescents in the Tashkent population (Republic of Uzbekistan) on a bone densitometer 2–3 days after fracture. Given the peculiarities of bone tissue metabolism and the rate of BMD loss, this group of examinees can be considered as part of the population with certain risk factors that led to the fracture. It was found that the most frequent fractures (60 %) occurred in boys and girls of primary school age. To assess the risk factors that could lead to a low-energy fracture, we evaluated BMD, vitamin D levels, and indices reflec–ting bone metabolism — calcium, phosphorus, and alkaline phosphatase. Of the 230 children examined with a fracture, 37.4 % had low BMD.
According to the literature, the prevalence of low bone mineral density (osteopenia) in children can be 20.5 ± 1.1 % and varies from 14.6 ± 2.3 to 30.3 ± 4.0 % depending on age, sex and place of residence [11]. The data we obtained were slightly higher than these figures. Low BMD may be associated with a growth spurt, accompanied by desynchronization of bone mineralization, uneven distribution and reduction of minerals in bone areas, which affects bone mass accumulation. In girls, peak bone mass is formed by 11–12 years, in boys — by 13–14 years. Insufficient mineralization, the presence of osteopenia at this age explains the increased bone fragility, and fracture affects the peak of bone mass formation [12]. The formation of peak bone mass is also affected by many external factors related to the diet, such as deficiency of calcium, magnesium and other macro- and microelements, vitamin D, proteins, as well as low physical activity, etc. These factors lead to impaired peak bone mass formation with subsequent problems in adulthood. 
According to the European study, 30–50 % of adolescents will have at least one fracture before the age of 17, and the risk of fracture is approximately 103–257 per 10,000 [13], which requires the identification of risk factors for low-energy fracture, among which MPCT studies occupy a special place. To assess BMD in children and adolescents, an adequate area for examination is the LS in the frontal plane. According to our data, BMD studies in the PF are less reliable, because 23.3 % of children would have remained undetected with low BMD if there were no BMD scores in the PF of the spine. Scanning accuracy of the proximal femur in children can be affected by scanning factors (positioning and motion) and analysis issues (presence of open growth areas, visualization of the fibula, and location of the area of interest), as well as the variability of the growing skeleton [14]. It is not recommended to use PF scans in other studies either [15]. There is evidence from a study of forearm BMD in boys that also shows that this skeletal segment may also reflect the risk of fracture to a lesser degree [16]. We analyzed the presence of low BMCT in children and adolescents of preschool, elementary, and high school age. Statistically significant results were obtained when analyzing the osteoporosis index only among girls of elementary and high school age. Statistically significant differences between boys and girls of elementary and high school age were revealed for the low BMD.
The BMI assessment revealed fractures of the forearm bones in 4.8 % of obese children and adolescents. There is evidence from a study showing that an increase in body weight often leads to fractures in the distal radius, which is associated with incomplete bone adaptation in children due to the higher forces applied to the bones during a fall [17].
A significant factor is vitamin D, insufficiency and deficiency of which affect calcium metabolism, the formation of peak bone mass, muscle tone and tendency to fall. In our study, we found that normal vitamin D values were found only in 19.3 % of girls (low in 80.7 %) and in 9.2 % of boys (low in 90.8 %) without clinical signs of rickets. There was evidence of serum vitamin D insufficiency (less than 20 ng/ml) 
in 48.8 % of prepubertal children aged 6–10 years [18]. These data suggest that laboratory-detected vitamin D deficiency may occur more frequently than clinically significant signs of rickets.
A correlation analysis was performed between BMD and vitamin D levels, and it was found that the relationship was direct (i.e., a low level of BMD had a low level of vitamin D) statistically significant in girls and boys of primary school age, and only in boys of high school age. These data indicate a role of vitamin D in mineralization and bone mass formation. Analysis of BMD and vitamin D in preschool children showed that the dependence of the signs was not statistically significant. This may be due to the small number of children in this group or other factors that require additional research. One of the most common risk factors for low BMD, along with vitamin D, is calcium deficiency. Dietary calcium intake is approximately 50 % of the recommended dietary intake. In our study, low serum calcium levels were present after fracture in 68.4 % of girls and 57.8 % of boys. Calcium levels in blood serum may have been low before the fracture, because calcium deficiency may be asymptomatic in the child for a long time. At the same time, calcium deficiency is one of the main risk factors of decreased BMD and hypocalcemia, which leads to increased secretion of parathyroid hormone and increased osteoclastic bone resorption. Due to resorption, calcium balance is restored, but bone quality is impaired and BMD is reduced. Phosphorus levels in 97.7 % of boys and 94.7 % of girls remained normal, but the calcium/phosphorus ratio (1 : 1) was compromised by the decrease in calcium.
Alkaline phosphatase was chosen for analysis because it is involved in regeneration, is produced by osteoblasts and plays an important role in mineralization, increases inorganic phosphate levels and decreases the concentration of the mineral formation inhibitor extracellular pyrophosphate [19]. Alkaline phosphatase levels in blood serum were ele–vated after fracture and surgical or conservative treatment in 93 % of boys and 89.5 % of girls. This can be considered as a positive factor indicating the activation of osteoblasts taking part in regeneration, their biosynthesis of the organic bone matrix (collagen, proteoglycans, etc.); in addition, alkaline phosphatase initiates calcium accumulation in bone cells, and low calcium levels may have a negative effect on regeneration.
The data obtained indicate the need to develop a comprehensive approach for early identification of children at risk for osteoporosis, which is important for timely diagnosis and, if necessary, initiation of treatment to prevent fracture risk. Continuous monitoring of BMD in children with low BMD and osteoporosis, improvement of rehabilitation measures with correction of nutrition, sufficient intake of calcium and vitamin D, adequate physical activity, etc. are necessary.
Study limitations. This study reflects the characteristics of children and adolescents with low-energy fractures in the population of Tashkent (Republic of Uzbekistan). Depending on place of residence and environment, BMD, vitamin D status may vary in severity.

Conclusions

60 % of 230 examined children and adolescents had fractures in primary school age, 29.1 % in older school age, and 10.9 % in preschool age. A direct correlation between BMD and vitamin D status was detected in boys of elementary and high school age and in girls of elementary school age. Low BMD, vitamin D and calcium-phosphorus metabolism disorders may be considered as predictors of fractures in children and adolescents.
 
Received 01.11.2022
Revised 06.12.2022
Accepted 10.12.2022

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