Decreased bone mineral density and alteration in biochemical bone metabolism markers in children affected by bone tumors after completion of therapy.

UNLABELLED: The aim of this study was to assess bone mineral density (BMD) and biochemical bone metabolism markers in patients with bone tumors after anti-cancer treatment. The study included 27 patients (median age 15 years) with malignant bone tumors and 27 healthy children. In all subjects, BMD and body composition were measured by dual-energy x-ray absorptiometry. Serum bone markers were determined by immunoenzymatic assays. After completion of treatment, patients with bone tumors had significantly decreased total and lumbar spine BMD. We observed lower calcium and vitamin D levels in patients and comparable values of bone turnover markers (carboxyterminal telopeptide of collagen type I - CTX, bone alkaline phosphatase - BALP and osteocalcin - OC) in both groups of children. However, the level of carboxylated osteocalcin (cOC) was significantly lower (p<0.01) and undercarboxylated OC (ucOC) was higher (p<0.05) in patients than in controls. Additionally, we observed similar values of anthropometric parameters in the subgroups of patients treated with methotrexate (MTX) or without MTX. In patients treated without MTX we found lower (p<0.05) ratio of cOC/ucOC, lower vitamin D level and higher CTX concentrations. Patients with bone tumors after anticancer treatment had decreased bone mineral density and alterations in bone metabolism markers with potential decrease in bone formation. KEYWORDS: bone cancer survivors, bone mineral density, bone formation markers, bone resorption markers, methotrexate.

Bone turnover markers, osteoprotegerin and RANKL cytokines in children with cystic fibrosis.

PURPOSE: Some scientific studies show decreased bone mineral density and increased fracture frequency in adult patients with cystic fibrosis (CF). The mechanism for early bone loss in CF patients are multifactorial: chronic pulmonary inflammation, malnutrition, reduced physical activity, delayed pubertal maturation. The aim of this study was to assess bone metabolism markers with special attention paid to osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) balance in CF children. MATERIAL AND METHODS: The study included 35 children with diagnosed CF and 35 healthy controls aged 5-9 years (median 7.0 years). Serum levels of fat soluble vitamins were measured by chemiluminescence (vitamin D) and HPLC (vitamins A, E) methods. Concentrations of bone metabolism markers were determined by immunoenzymatic assay. RESULTS: Mean levels of fat soluble vitamins (A, D, E) were lower in patients with CF compared to controls. In CF children we observed a significant (p<0.01) decrease in concentration of bone formation marker (osteocalcin) and similar bone resorption markers (CTX, TRACP5b) in comparison with healthy children. The serum level of OPG was significantly lower (p<0.05) and RANKL nearly 2-fold higher in patients with CF than in the healthy ones. The ratio of OPG to RANKL was about 2-fold lower in children with CF compared to healthy peers (p<0.01). CONCLUSION: In CF children, an imbalance between bone formation and resorption processes occurs. An increase serum RANKL concentration coexisting with lower levels of OPG may be associated with intensification of bone resorption.

Alterations in markers of bone metabolism and adipokines following a 3-month lifestyle intervention induced weight loss in obese prepubertal children.

BACKGROUND: Adipokines may influence bone metabolism in children, but this phenomenon is not well understood. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. MATERIALS AND METHODS: We determined serum leptin, soluble leptin receptor (sOB-R), adiponectin, BALP (bone alkaline phosphatase), CTX-I (C-terminal telopeptide of type I collagen), body composition and bone mineral density (by dual-energy X-ray absorptiometry) in 100 obese prepubertal children before and after 3 months of lifestyle intervention (low-energy diet, physical activity). The control group consisted of 70 non-obese children. RESULTS: Obese children had higher BALP activity by about 20% (p<0.001) and similar value of CTX-I compared with non-obese children. After weight loss (-0.96 BMI-SDS mean change), the BALP value in obese patients decreased (p<0.001), whereas CTX-I concentration was unchanged. Changes in BALP were positively correlated with changes in BMI (Body Mass Index) (r=0.352, p<0.001), but not associated with adipokine levels. Trend analysis using SDS-BMI subgroups showed that greater reduction of body mass was associated with a greater decrease of BALP (p=0.035) and leptin values (p<0.001), as well as a greater increase of sOB-R (p<0.003). CONCLUSIONS: Obesity during the prepubertal period is associated with an alteration in the adipokines profile and greater whole-body bone mass as a result of increased bone formation rather than reduced bone resorption. Changes in bone metabolism during lifestyle intervention seem to be related to weight loss but not to changes in adipokines. Further studies should elucidate the influence of long-term therapy on bone mass in childhood.

Clinical utility of biochemical bone turnover markers in children and adolescents with osteosarcoma.

PURPOSE: Biochemical markers of bone turnover reflecting the intensity of all bone remodeling processes in skeleton are important for fast and non-invasive assessment of bone formation and resorption processes. They can be used in terms of both physiological and pathological states. The aim of this study was to investigate if bone metabolism markers can be clinically useful for monitoring of treatment in children and adolescents with osteosarcoma. MATERIAL/METHODS: The study consisted of 55 patients (median age 15 years) with osteosarcoma and 60 healthy age matched counterparts. Serum bone turnover markers (bone alkaline phosphatase - BALP, osteocalcin - OC and C-terminal telopeptide of type I collagen - CTX) were analyzed by immunoenzymatic methods in patients at time of diagnosis, during treatment and after therapy. RESULTS: We observed that before treatment the concentration of OC in patients with osteosarcoma was significantly lower (p<0.05) compared to that obtained in healthy children, however, BALP and CTX were at a similar level. During chemotherapy the values of bone formation and resorption markers significantly decreased by about 20-30%. After therapy we observed different concentrations of all bone turnover markers in patients with favorable and unfavorable prognosis. Median values of OC and BALP were over twofold higher in patients with progression as compared to patients with remission of disease (p<0.01 and p<0.001, respectively). Patients with poor prognosis had also higher serum concentration of bone resorption marker in comparison to patients with remission (p<0.01). CONCLUSIONS: Presented results suggest that bone turnover markers identify changes in bone metabolism in patients with osteosarcoma during anticancer therapy. These markers due to the non-invasive methods and their specificity might be useful in monitoring of clinical treatment of osteosarcoma patients.

Serum markers of bone turnover in children and adolescents with classic galactosemia.

PURPOSE: Classic galactosemia is an inherited metabolic disease resulting from galactose-1-phosphate uridyltransferase (GALT) deficiency. Dietary lactose exclusion reverses many clinical manifestations of acute phase of the disease. Unfortunately most of the patients, despite dietary treatment, develop long-term complications among them disturbances of bone mineralization resulting in decrease of bone mineral density (BMD). The aim of our study was to assess bone formation and resorption processes with bone turnover markers in children and adolescents with galactosemia. MATERIALS AND METHODS: We studied 62 galactosemic children (mean age+/-SD 5.9+/-2.7 years) and adolescents (mean age+/-SD 15.6+/-2,4 years). The clinical diagnosis had been confirmed by the absence of GALT activity in erythrocytes. All patients were diagnosed in the neonatal period and had good dietary control. Healthy children (n=70) were the reference group. Serum osteocalcin (OC), bone alkaline phosphatase (BALP), collagen type I crosslinked C-telopeptide (CTX-I), 25(OH)D metabolite of vitamin D were determined by ELISA assays. RESULTS: We observed similar mean values of bone formation markers in children with galactosemia as compared to the age-matched controls. The level of bone resorption marker CTX-I in these patients was lower by about 20% (p<0.001) than in healthy children. On the contrary we obtained slightly higher values of CTX-I in adolescents with galactosemia in comparison to the age-matched controls. In these patients the values of OC and BALP were significantly higher than in healthy adolescents (111.8+/-52.1 microg/L versus 82.3+/-43.0 microg/L, p<0.02; and 95.4+/-45.7 U/L versus 72.6+/-40.6 U/L, p<0.05 respectively). CONCLUSION: Our results suggest that bone turnover in galactosemic patients elevates from childhood to adolescence, whereas in healthy individuals there is a decline during aging. Further studies on adults with galactosemia are necessary to assess bone status in these patients.

Serum concentration of biochemical bone turnover markers in vegetarian children.

PURPOSE: In general, most children on well-planed vegetarian diets can achieve normal growth and development. However, elimination of animal products from the diet decreases the intake of some essential nutrients, such as calcium and vitamin D, and may influence bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of this study was to investigate the serum concentrations of biochemical bone turnover markers in prepubertal vegetarian children. MATERIAL AND METHODS: We examined 50 children on vegetarian and 50 on omnivorous diets aged 2-10 years. Dietary constituents were analyzed using a local nutritional program. Serum bone formation (OC, BALP) and resorption (CTX) markers were determined by specific enzyme immunoassays (ELISA) and 25-hydroxyvitamin D by the chemiluminescence method (CLIA). RESULTS: The average daily energetic value and the percentage of energy from protein, fat and carbohydrates in the diets were similar in both groups of children and were within the recommended range. The vegetarian children showed about a two-fold lower daily intake of calcium and vitamin D than their omnivorous counterparts. The level of 25-hydroxyvitamin D in the serum of vegetarian children was also nearly 2-fold lower compared with omnivores. In vegetarians, as compared to non-vegetarians, mean serum concentrations of OC, BALP and CTX were lower by about 20%, 10% and 15%, respectively. CONCLUSION: Our preliminary results suggest that an inadequate dietary intake of calcium and vitamin D may impair bone turnover rate in vegetarian children. The parameters of bone metabolism should be monitored in these children in order to prevent bone abnormalities.

Serum homocysteine, folate, vitamin B12 and total antioxidant status in vegetarian children.

PURPOSE: The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. MATERIAL AND METHODS: The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. RESULTS: Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. CONCLUSIONS: The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth.

[Homocysteine and some lipid parameters in hypercholesterolemic children]. / Homocysteina i wybrane parametry przemian lipidowych u dzieci z hipercholesterolemia.

High serum homocysteine (tHcy) concentration is increasingly recognised as independent risk factor for atherosclerosis, early coronary heart disease (CHD) and other vascular diseases. It has been proved that adult cardiovascular disease begins in childhood. In the presented studies we determined concentrations of homocysteine, lipids and lipoproteins in plasma of hypercholesterolemic and normocholesterolemic children. In hypercholesterolemic children total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides were significantly higher, whereas HDL cholesterol and apolipoprotein A-I were lower in comparison to the control group. Total serum homocysteine in children with positive family history for cardiovascular disease CHD(+) was significantly higher than in the control groups, and in CHD(-) group. It was respectively 7.3 micromol/1 versus 5.45 micromol/l versus 5.21 micromol/l. The results obtained in our study indicate that in hypercholesterolemic children with positive family history for CHD, the concentration of tHcy can be considered as a separate predictive risk factor for premature cardiovascular disease.

[Level of retinol and beta-carotene in plasma of smoking and non-smoking women]. / Poziom retinolu i beta-karotenu w osoczu krwi palacych i niepalacych kobiet ciezarnych.

Cigarette smoking during pregnancy generates many oxidants and free radicals and it has been implicated in cellular damage. Retinol and its provitamin beta-carotene are natural factors protecting cells from damaging influence of free oxygen species. The aim of our study was the assessment of vitamin A and beta-carotene levels in plasma of smoking and non-smoking pregnant women. Assignment the groups was based on the concentration of serum cotinine. In the presented studies the mean level of serum cotinine in smoking pregnant women was 1326 +/- 790 micrograms/l (range 350-1930 micrograms/l). In the group of tobacco abstinents the level of cotinine was in a range of 0-60 micrograms/l. Plasma concentrations of retinol and beta-carotene were measured by high pressure liquid chromatography (HPLC). Plasma level of vitamin A was lowered by 20% and was 1.64 +/- 0.42 mumol/l and 2.06 +/- 0.58 mumol/l in smoking and abstinent groups respectively. Women who smoke during pregnancy also have significantly lower levels of beta-carotene in plasma (1.9 +/- 0.5 mumol/l) than non-smokers (2.4 +/- 0.6 mumol/l; p < 0.001). We have observed that plasma concentration of beta-carotene has decreased since 21 gestation week in smokers while in abstinent group increased during pregnancy. The increase of plasma level of beta-carotene indicates that their physiological requirement is satisfied by standard vitamins supplementation. The reduced concentrations of plasma retinol and beta-carotene suggest that consumption of these antioxidants for neutralization of free radicals present in cigarette smoking is enhanced. The observed changes indicate that vitamins intake in smoking pregnant women should be carefully controlled.

Antioxidant status in erythrocytes of cystic fibrosis children.

Activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes of cystic fibrosis children were studied in order to estimate the severity of their deficiency. Our results point to increased susceptibility of erythrocytes of cystic fibrosis subjects to oxidative injury and indicate that the antioxidant status of patients should be carefully monitored.

[Levels of lipid peroxides and of some antioxidants in placenta and cord blood of newborns whose mothers smoked during pregnancy].

Cigarette smoking during pregnancy increases the risk of oxidative damage and induces not only intrauterine foetal growth retardation, but also causes disturbances in postnatal growth and development. In the presented studies oxidative damage was estimated through the measurement of lipid peroxides concentration and the level of some antioxidants in placenta and in cord blood of newborns whose mothers smoked during pregnancy. We observed that the concentration of lipid peroxides was higher in cord blood and in placenta tissue (8%) than in the newborns of non-smoking mothers, but the activity of superoxide dismutase and glutathione peroxidase were lower by 20% and 16% respectively. Plasma level of vitamin A (p<0.005), vitamin E (p<0.05), fS-carotene (p< 0.0001) and total plasma antioxidant capacity (p<0.05) were significantly lower in the newborn of smoking than the non-smoking mother group. It is suggested that placental tissue protected the foetus against oxidative stress, but not sufficiently. Antioxidant activities of cord blood may also be insufficient in dismutation of free radicals and their detoxication in order to protect newborns against smoking dependent metabolic disturbances.

[Compensatory antioxidant activity in blood of women whose pregnancy is complicated by cigarette smoking]. / Kompensacyjna aktywnosc przeciwutleniajaca krwi kobiet w ciazy powiklanej paleniem tytoniu.

In pregnancy complicated by the cigarette smoking the risk of oxidative damage depends not only on the amount of physiologically enhanced free oxygen species but may be affected by intoxication with tobacco smoke radicals. In the presented studies oxidative damage was estimated through measurement of lipid peroxidation, level of total antioxidant activity and selected antioxidants in plasma and erythrocytes of non-smoking and smoking pregnant women. No differences were found between those two groups in the level of lipid peroxidation and antioxidant activity. Plasma concentration of vitamin A was lower by 15% in smoking than in non-smoking women but vitamin E level did not change. In erythrocytes of the smoking group, concentration of reduced glutathione was 35% higher than in the non-smoking group but activity of glutathione peroxidase and concentration of vitamin E were the same. The observed changes indicate that protection of erythrocytes against free radicals may be sufficient to prevent lipid peroxidation and may manifest local and adaptive response of metabolism for tobacco smoking by pregnant women.