ABSTRACT
OBJECTIVE: identification of clinical and metabolic characteristics of osteogenesis and factors affecting bone mineral density (BMD) in children living in radioactively contaminated territories (RCT) after the ChNPP accident for the use of therapeutic and preventive measures aiming to reduce the incidence of disorders. MATERIALS AND METHODS: Children aged 4 to 18 years old (n = 539) were involved in the study within 4 age groups, namely under 7 years old, 7-10 years old, 10-14 years old, older than 14 years old. Studied parameters in children with a reduced BMD (85-65 relative units and under 65 relative units) were estimated vs. the normative BMD (100-85 relative units) cases. Diagnosis of osteopenia and osteoporosis in children was established according to the BMD T-index. Family history of the relatives of children was studied. Body weight at birth, fractures of the long bones, complaints of osalgia, jaw anomalies, dental caries, presence of obesity, and hypermobility syndrome (HMS) were assessed. Peripheral blood biochemical tests were performed featuring the serum total protein, alkaline phosphatase (APh), calcium, vitamin D, creatinine, serum iron (SI), ferritin, cortisol, pituitary thyroid-stimulating hormone (TSH), and free thyroxine (FT4) assay. BMD was measured and radiation doses in children were reconstructed. RESULTS: BMD depended on the age of children. A direct correlation was established between the cholelithiasis and urolithiasis incidence (Ñ < 0.01), cancer and endocrine diseases (Ñ < 0.05) in the relatives of children that had BMD under 65 relative units. Dental caries developed more often (Ñ < 0.05), while obesity was less frequent (Ñ < 0.05) in the subjects with BMD < 65 relative units. A direct correlation was established between the level of serum creatinine and BMD (Ñ < 0.01), and there was an inverse correlation between the serum APh level and BMD (Ñ < 0.001).Every third child had a vitamin D deficiency. Fractures of long bones and increased content of SI and TSH were characteristic for the children having got osteopenia (BMD within 85-65 relative units), while besides a predisposition to bone fractures the higher levels of SI, APh, cortisol both with calcium deficiency were found in children with osteoporosis (BMD < 65 relative units) compared to the general group with a similar BMD. An increased incidence of HMS was characteristic too. Radiation doses in children with osteopenia were higher than in those with osteoporosis: (1.17 ± 0.09) mSv and (0.92 ± 0.06) mSv respectively (Ñ < 0.05). No correlation was found between the radiation doses and clinical signs, blood biochemistry or BMD. CONCLUSIONS: Study of the functional mechanisms of bone structures in children, depending on their metabolism, had made it possible to reveal the factors that affect bone formation in children living in RCT after the ChNPP accident, and to form the population groups for the timely application of therapeutic and preventive measures aiming to reduce the incidence of disorders of musculoskeletal system.
Subject(s)
Bone Diseases, Metabolic , Dental Caries , Fractures, Bone , Osteoporosis , Child , Infant, Newborn , Humans , Child, Preschool , Adolescent , Thyroid Gland/diagnostic imaging , Thyroid Gland/metabolism , Calcium , Hydrocortisone , Bone and Bones/diagnostic imaging , Osteoporosis/diagnostic imaging , Osteoporosis/epidemiology , Osteoporosis/etiology , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/etiology , Thyrotropin , ObesityABSTRACT
OBJECTIVE: assessment of clinical-hematological and metabolic-biochemical parameters of the of bone tissue and hormonal regulation depending on the serum iron content and radiation dose values in children living on radiologically contaminated territories after the ChNPP accident in Ukraine. MATERIALS AND METHODS: Children (n = 271) living on radiologically contaminated territories (RCT) of Ukraine were involved in the study. Three study groups were formed according to the serum iron level (SIL), namely group I with SIL 10.0-22.0 µmol/l (n = 92), group II with SIL 23.0-34.0 µmol/l (n = 144), and group III with SIL above 35.0 µmol/l (n = 35). Diseases in the family tree, bodyweight at birth, complaints on osalgia, bone fractures, jaw anomalies, dental caries, and obesity were accounted. Morphometric parameters of erythrocytes and hemogram elements were analyzed. Creatinine, alkaline phosphatase, calcium, total protein, iron, cholesterol, bilirubin, and transaminases were assayed in blood serum. The urine content of the 19 free amino acids, serum content of the free thyroxine (FT4), pituitary thyroid-stimulating hormone (TSH), and cortisol were assayed both with bone tissue density. Individual radiation doses were calculated. RESULTS: In 12.9 % of cases the SIL was > 35.0 µmol/l. Relatives with endocrine diseases were often present in the family tree of children with SIL > 23.0 µmol/l. There were increased urine content of the free amino acids (p < 0.05) and signs of protein degradation under high SIL. Contents of amino acids involved in collagen synthesis and antioxidant status (alanine, serine, glutamine, aspartic acid) and iron metabolism (arginine, leucine) were assayed at the highest levels (p < 0.05). Urinary levels of valine, lysine, and methionine, which are associated with iron metabolism, were decreased (p < 0.05). An inverse correlation (rs = -0.58; p < 0.01) was established between the serum TSH and cortisol levels regardless of the SIL. Serum TSH level directly correlated with urine content of amino acids involved in collagen synthesis. An inverse correlation (rs = -0.55; p < 0.001) was established between the serum TSH level and urine content of tyrosine that is essential for the thyroid hormone (triiodothyronine and thyroxine) synthesis.Cortisol was found having a negative effect on protein synthesis. Inverse correlation was established between the serum cortisol level and urine content of the free amino acids essential for collagen synthesis. There was no dependence of the average radiation dose values on the SIL. An inverse correlation was determined between the patient's radiation dose and SIL > 35.0 µmol/l (rs = -0.29; p < 0.05). CONCLUSIONS: The increased SIL in children living on RCT may occur due to both a genetic predisposition and the acquired factors driving protein and mineral metabolism of bone and their hormonal regulation.
Subject(s)
Hydrocortisone , Thyroxine , Child , Infant, Newborn , Humans , Ukraine , Thyrotropin , Iron , Amino Acids , CollagenABSTRACT
OBJECTIVE: Elucidation of relationship between the levels of thyroid-stimulating hormone (TSH), free serum thyroxine, serum and urine cortisol and parameters of erythroid lineage of hematopoiesis to estimate the thyroid functionin children of prepubertal, pubertal, and postpubertal age permanently residing under a low-dose radiation exposureto determine the premorbid state of thyroid function. MATERIALS AND METHODS: Children aged 3 to 18 years old (n = 203) living in the most intensively radionuclide-contaminated regions of Kyiv, Zhytomyr and Chornihiv oblasts of Ukraine after the Chornobyl NPP accident wereenrolled. Complaints of ossalgia, arthralgia, fatigue, bone fractures in the history, bone dysembryogenetic stigmata,hypermobility syndrome degree, and types of somatic diseases were taken into account. Peripheral blood countparameters, biochemical indices of blood serum were studied, namely the levels of total protein, cholesterol, creatinine and alkaline phosphatase activity. Levels of the free thyroxine, pituitary TSH, serum and daily urine cortisol, anddoses of radiation exposure were determined. RESULTS: The radiation dose values in children ranged from (0.35 ± 0.09) mSv to (0.54 ± 0.12) mSv. There was nodifference between the parameters of erythroid lineage of hematopoiesis depending on radiation dose. At the levels of serum TSH up to 1.0 µIU/ml no correlation was found with cortisol levels; at TSH levels of 1.0-3.0 µIU/ml thecorrelation coefficient was r = 0.31; at TSH levels higher than 3.0 µIU/ml the correlation coefficient was r = 0.61probably indicating a compensatory role of adrenal cortex in children at risk of thyroid disease development. In children with joint hypermobility grade II there was a higher incidence of dentofacial anomalies (χ2 = 6.9), deformitiesof lower extremities (χ2 = 6.9), and dental caries (χ2 = 4.3) (p < 0.05). There was a direct correlation between theserum TSH level (over 3 µIU/ml) and micrognathia (brachygnathia) (r = 0.62) indicating the impact of thyroid disease on dentofacial development. The TSH at a level of upper limit of the reference range values may contribute toa decreased RBC count in peripheral blood, increased average volume and hemoglobin content in erythrocyte beingassociated with the initial manifestations of thyroid dysfunction. CONCLUSIONS: Abnormal endocrine regulation of hematopoiesis affects the connective tissue, stromal microenvironment of bone marrow, and accordingly the erythroid branch of hematopoiesis in children, which may be relevant inthe development and course of oncohematological diseases.
Subject(s)
Arthralgia/epidemiology , Chernobyl Nuclear Accident , Dental Caries/epidemiology , Fatigue/epidemiology , Fractures, Bone/epidemiology , Hematopoiesis/radiation effects , Joint Instability/epidemiology , Adolescent , Arthralgia/blood , Arthralgia/etiology , Arthralgia/pathology , Cell Lineage/radiation effects , Child , Child, Preschool , Dental Caries/blood , Dental Caries/etiology , Dental Caries/pathology , Erythroid Cells/pathology , Erythroid Cells/radiation effects , Fatigue/blood , Fatigue/etiology , Fatigue/pathology , Female , Fractures, Bone/blood , Fractures, Bone/etiology , Fractures, Bone/pathology , Humans , Hydrocortisone/urine , Joint Instability/blood , Joint Instability/etiology , Joint Instability/pathology , Male , Puberty/blood , Puberty/radiation effects , Radiation Dosage , Radiation Exposure/adverse effects , Radiation, Ionizing , Radioisotopes , Thyroid Gland/pathology , Thyroid Gland/radiation effects , Thyrotropin/blood , Thyroxine/blood , Ukraine/epidemiologyABSTRACT
OBJECTIVE: Evaluation of proliferation and differentiation processes of progenitor cells in bone marrow by the com position of elements of erythroid, granulocyte and platelet branches of hematopoiesis on the treatment stages in children with acute lymphoblastic leukemia (ALL), who were exposed to radiation from the Chornobyl NPP accident. MATERIALS AND METHODS: The 46 children with ALL were studied, who lived in Kyiv, Zhytomyr and Chernihiv regions. Studies were conducted before the start of chemotherapy (ChT), on the 33 day of ChT (phase I), and after the com pletion of ChT (phase II). Exposure doses of patients, hemogram and myelogram parameters both with indices of mat uration of progenitor cells were evaluated. Signs of dysplasia of hematopoietic branch elements were revewed. RESULTS: The 46 patients were studied. They have had the B ALL, namely pro B ALL (n=5), «common type¼ (n=36), pre B ALL (n=3), and T ALL in 2 other cases. In a debut of ALL the bone marrow was represented by lymphoblasts. Along with ChT conduction the bone marrow hematopoiesis recovered by such types, as erythroid, granulocyte, gran ulocyte whith monocytes, and uniform, when the cells number of all branches was within a normal quantity. At the phase ÐÐ of ChT the number of patients with hematopoiesis recovery by erythroid type decreased and number of chil dren with activation of granulocyte branch of hematopoiesis increased. In children with pro B ALL the number of erythroid elements was higher than normative at both ChT phases. A direct correlation was established between the number of myelokaryocytes (Mkc) and megakaryocytes (Mgkc) in both phase Ð and phase ÐÐ of treatment (Rs = +0.72; Rs = +0.56, respectively). There was no correlation between the radiation dose in patients (3.73 ± 0.12 mSv) and studied parameters. CONCLUSIONS: Types of bone marrow recovery were established in ALL patients after the ChT indicating to the differ ent kinetic pathways of hematopoietic progenitor cells. Evaluation of reasons of prevalence of some hematopoietic branches will allow to reveal their role in leukemogenesis and to correct the treatment programs.
Subject(s)
Hematopoiesis , Accidents , Blood Platelets , Bone Marrow Cells , Child , Granulocytes , Hematopoietic Stem Cells , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Radiation, IonizingABSTRACT
OBJECTIVE: To investigate the aminoacid composition in the stromal fibroblasts of bone marrow and indexes of hemogram in children with acute lymphoblastic leukemias, which exposed to radiation from the Chornobyl accident, for evaluation of the median survival. MATERIALS AND METHODS: In the study 54 patients with acute lymphoblastic leukemia, residents of Kyiv, Zhytomyr and Chernihiv regions of Ukraine were involved. Effectiveness of stromal fibroblasts colony forming units of bone marrow and aminoacid composition of fibroblasts were studied. Bone marrow examination was conducted on day33 and after stop of chemotherapy, the median survival of patients and exposure dose were evaluated. RESULTS: In children with acute leukemias effectiveness of stromal fibroblasts of bone marrow was 2-2,3 times lower than normative. Correlation (rs = +0,83) between the number of erythroid progenitor cells in the bone marrow and proline content in stromal fibroblasts established . The correlation between patients median survival and number of granulocytes in myelogram (rs = + 0,82) was proven. Mean exposure doses in patients was (5,86 ± 1,11) mSv and it did not correlate with myelogram results, effectiveness of stromal fibroblasts of bone marrow and median survival. CONCLUSIONS: The median survival of patients with acute leukemias depends on the content of amino acids in stro mal fibroblasts of bone marrow and recover of hematopoiesis after chemotherapy.