Bone biopsy results and serum bone turnover parameters in uremic children

The aim of the study was to evaluate the prevalence of renal osteodystrophy types in children undergoing haemodialysis and continuous ambulatory peritoneal dialysis and to assess the usefulness of biochemical parameters in diagnosis of renal osteodystrophy. Bone biopsy and measurements of serum parathormone (iPTH) level, alkaline phosphatase (AP), osteocalcin (OC), procollagen 1C, calcium and phosphorus levels were performed in 51 children aged 11.5 +/- 2.9 y with end-stage renal failure. Renal osteodystrophy (ROD) was diagnosed as follows: adynamic bone disease (ABD) in 14 (27%); normal bone histology (NB) in 19 (37%), osteomalacia (OM) in 1 (2%), mixed lesion (Mix) in 5 (10%) and hyperparathyroidism (HP) in 12 (24%) children. There was no difference in prevalence of ROD types between children on CAPD and HD. We found significant differences in the mean value of iPTH, OC levels and AP activity in HP vs NB and HP vs ABD. The prevalence of ABD was significantly higher in patients with PTH below 50 pg/ml than in patients with PTH above 50 pg/ml (p < 0.05). In 69% of children with NB the iPTH level was between 50 and 150 pg/ml. Most HP cases (75%) were diagnosed in patients with iPTH above 200 pg/ml. A high correlation between BFR and iPTH, BFR and OC, AP levels was found. CONCLUSION: The biochemical markers of bone turnover have only limited value in the differentiation of renal osteodystrophy types.     

早产儿维生素D及骨代谢指标水平的相关性研究

目的探讨早产、维生素D和骨代谢指标水平的相关性。方法收集2012年11月至2013年10月于中国医科大学附属盛京医院出生的814例新生儿为研究对象,其中24例为妊娠28~32周的早产儿(重度早产组),134例为妊娠32~36周的早产儿(轻度早产组),656例为妊娠满37周的足月儿(足月产组)。使用25-(OH)-D、骨保护素(osteoprotegerin,OPG)、甲状旁腺激素(parathyroid hormone,PTH)和Ⅰ型胶原C末端肽(C-telopeptides typeⅠcollagen,CTX)对应的ELISA试剂盒完成25羟基维生素D(25-(OH)-D)血清浓度及骨代谢标志物浓度的测定。结果足月产组体重、身长、头围、胸围大于重度和轻度早产组(P<0.01)。三组间的维生素D和PTH水平差异有统计学意义(P<0.01)。重度早产组与足月产组、重度早产组与轻度早产组中的OPG水平存在差异,且有统计学意义(P<0.01)。早产组中,25-(OH)-D浓度与OPG、CTX的浓度呈正相关(r=0.563,P<0.01;r=0.581,P<0.001),与PTH浓度呈负相关(r=-0.621,P<0.001),OPG与PTH的浓度呈负相关(r=-0.518,P<0.001),与CTX浓度呈正相关(r=0.653,P<0.001),PTH与CTX浓度呈负相关(r=-0.520,P<0.001)。结论成骨活动障碍及破骨活动亢进可能是导致早产儿易患代谢性骨病的关键因素,维生素D缺乏可能是代谢性骨病的原因之一。监测血清25-(OH)-D和骨代谢指标水平能较好地反映新生儿(特别是早产儿)的骨代谢状态。     

骨钙素、Ⅰ型前胶原羧基端前肽、胰岛素样生长因子-1及其相关激素与胎儿骨发育的关系

目的 探讨骨钙素(OC)、Ⅰ型前胶原羧基端前肽(PICP) 及胰岛素样生长因子.1(IGF.1)等激素水平与胎儿骨生长发育的关系.方法 选择本院2008年10月-2009年10月收治的新生儿80例.男41例,女39例;胎龄28～42周.根据不同出生体质量分为小于胎龄(SGA)儿组22例,适于胎龄(AGA)儿组36例及大于胎龄(LGA)儿组(22例).胎儿娩出后,胎盘娩出前抽取其脐静脉血6 mL,采用放射免疫分析法测定其血清OC、IGF.1及甲状旁腺激素水平,酶联免疫吸附法检测其脐血PICP水平;同时检测其血钙、磷、ALP水平,测量新生儿生长参数,计算体质量指数(BMI).结果 1.脐血OC水平在SGA儿组、AGA儿组、LGA儿组间比较差异有统计学意义(P=0.000),LGA儿组显著高于AGA儿及SAG儿组(P＜0.01,0.001);脐血OC水平与出生体质量、头围、BMI呈正相关(Pa＜0.05),与身长无明显相关性(P＞0.05).2.LGA儿组脐血IGF.1水平显著高于AGA儿及SAG儿组,3组间比较有统计学差异(P=0.002);脐血IGF.1水平与出生体质量、头围、BMI水平均呈正相关(Pa＜0.05),与身长无明显相关性(P＞0.05).3.AGA儿组、LGA儿组脐血PICP水平明显高于SGA儿组,但3组间无统计学差异(P=0.070).脐血PICP、PTH水平与生长参数各指标水平均无直线相关关系(Pa＞0.05),偏相关分析脐血PICP与出生体质量、头围、BMI均呈正相关(r=0.239、0.250、0.306,Pa<0.05).4.脐血OC水平与PICP、IGF.1水平均呈正相关(Pa＜0.05),OC、PICP与PTH、ALP水平之间均无明显相关(Pa＞0.05).5.3组脐血钙、血磷、ALP水平均无统计学差异(Pa＞0.05).结论 SGA儿低血清OC、PICP水平与骨形成活动下降相关,脐血OC、PICP及IGF.1可作为评价胎儿骨骼生长发育的临床指标之一.     

Erythropoietin in children with chronic renal failure on dialytic and non-dialytic therapy

The serum values of erythropoietin and relationship with hemoglobin was studied in 29 children with chronic renal failure. 10 of the patients were receiving continuous ambulatory peritoneal dialysis (CAPD), 12 were on regular haemodialysis treatment (RHT) and 7 children were not on any form of dialysis treatment (ND). Serum erythropoietin was estimated using fetal mouse liver bioassay. The mean serum erythropoietin concentration in the three groups of patients were within the normal range but were inappropriately low for the degree of anemia (CAPD 19.6 +/- 8.0 mu/ml, RHT 25.7 +/- 13.2 mu/ml, ND 21.9 +/- 11.0 mu/ml. The haemoglobin value of (7.0 +/- 1.3 gm/dl) in the CAPD group was higher than in the RHT group (6.4 +/- 1.5 gm/dl), but this difference was not statistically significant (p greater than 0.1). In the non-dialysed patients, the mean haemoglobin value was 11.32 +/- 2.31 gm/dl and this was significantly higher than the values in the CAPD and RHT patients (p less than 0.05). No correlation was found between serum erythropoietin and haemoglobin in the three groups of patients.     

Type I collagen N-telopeptide variation in adolescents receiving oral isotretinoin for severe acne

The prolonged use of retinoids has been reported to be associated with changes of bone biochemical markers and toxic skeletal effects. Among collagen markers, type I collagen N-telopeptide (NTx) is present in all tissues that contain type I collagen, mostly in bone and in cutaneous tissue. It is a reliable indicator of bone resorption in metabolic bone disease, but has not previously been investigated in dermatological diseases during retinoid therapy. Isotretinoin, a synthetic 13-cis-retinoic acid, is highly effective in the treatment of severe acne vulgaris. We evaluated the effect of low-dose short-term oral isotretinoin treatment on bone remodeling markers in 10 adolescents (mean age 17.8 years) affected by severe acne. We measured urinary NTx as a marker of bone resorption, alkaline phosphatase (ALP) and osteocalcin (OC) as markers of bone formation, parathyroid hormone (PTH) and metabolites of vitamin D (25OH-D3 and 1,25(OH)2D3). Clinical and laboratory tests were performed before and after three months of isotretinoin treatment at the dosage of 0.5 mg/kg/day. All patients showed a good clinical response to the treatment (7/10 marked improvement, 3/10 mild improvement). No changes were detected in serum PTH, 25OH-D3, 1,25(OH)2D3, OC and ALP, while urinary NTx concentrations were significantly reduced (p < 0.05). In conclusion, the lack of change in PTH, OC, ALP and vitamin D metabolites and the absence of increase of NTx suggest no bone effect of the isotretinoin treatment. The decrease of urinary NTx could be due to the effect of isotretinoin on the cutaneous component of type I collagen. Severe acne in the active inflammatory phase could change the levels of this marker. Thus, short-term low-dose oral isotretinoin is an effective and safe treatment for severe acne.     

Serum osteocalcin and bone alkaline phosphatase in healthy children in relation to age and gender

Biochemical markers of bone formation are important in the study of growth and skeletal metabolism. However, interpretation of their values for children and adolescents is difficult because they depend on many factors such as age, gender, pubertal stage, race, nutritional and health status, specificity of assays and others. Therefore, age and sex specific reference ranges for bone formation markers must be established in a defined paediatric population. The purpose of this study was the investigation of normal serum concentration of osteocalcin (OC) and bone alkaline phosphatase (BALP) in Polish children aged 2-18 years. We studied 121 healthy children (56 girls, 65 boys) divided into 3 age groups of both genders: prepubertal, pubertal and postpubertal. The level of OC was determined by N-MID Osteocalcin One Step ELISA kit (Osteometer Bio Tech, Denmark) and the activity of BALP was measured using an enzyme immunoassay Alkphase-B kit (Metra Biosystems, USA). We observed, that both formation markers showed sigmoid regression curves with increasing age. The peak values of OC and BALP occurred during puberty in girls aged 9-13 years (115.6 +/- 21.3 ng/ml; 108.8 +/- 23.6 U/L) and in boys aged 10-15 years (117.8 +/- 22.3 ng/ml; 118.4 +/- 24.5 U/L). In all children after puberty, we observed a gradual lowering of both markers. However, girls showed decreased postpubertal values of OC and BALP 2-3 years earlier than boys, indicating the earlier completion of puberty in girls. The correlation between OC and BALP was statistically significant (r=0.612; p<0.001) in tested children. The results of this study may establish the reference values for bone turnover markers in Polish healthy children, which will be useful in the diagnosis and monitoring of therapy in bone diseases.     

Correlation among markers of renal osteodystrophy in pediatric hemodialysis patients

Serum levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium (Ca2+) have been used to evaluate renal osteodystrophy (RO) in adult patients undergoing dialysis. Osteocalcin (BGP) is a bone protein which also serves as a marker for bone turnover. Serum BGP levels correlate positively with rates of bone turnover and serum concentrations of PTH, AP, and Ca2+ in various studies of adult end-stage renal disease (ESRD) patients, whereas other studies reveal BGP to be a poor indicator of bone turnover in ESRD. RO is a significant problem in pediatric ESRD patients; however, there have been few studies evaluating the correlation of markers for RO in children with ESRD. We measured serum PTH, AP, Ca2+, and BGP levels in a group (n=23) of pediatric patients with ESRD and assessed the correlation among the markers. There was a positive correlation between serum PTH and AP (r=0.658, p<0.001). In contrast, there was no correlation between either serum Ca2+ or BGP, and either PTH or AP. The correlation between Ca2+, BGP and either PTH or AP was unaffected by growth in our patient population. Finally, neither age nor pubertal stage improved the correlation between either Ca2+ or BGP, and either PTH or AP. We conclude that serum PTH and AP are useful markers for RO, whereas calcium and BGP levels should not be used to evaluate RO in pediatric ESRD patients.     

Biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialyzed children

In this study we investigated the value of biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialysis patients. The study was carried out in 22 chronic renal failure patients (mean age: 16.1 +/- 4.5) being treated with chronic dialysis. There were three groups according to intact parathormone (iPTH) levels: Group I (n: 6): iPTH levels were less than 200 pg/ml; Group II (n: 9): iPTH levels were between 201 and 500 pg/ml; and Group III (n: 7). iPTH levels were higher than 501 pg/ml. We investigated iPTH, bone alkaline phosphatase, total serum alkaline phosphatase, osteocalcin, serum type 1 procollagen peptide (PICP) and insulin-like growth factor-1 (IGF-1) levels in all patients. In group III mean bone alkaline phosphatase level (126.0 +/- 10.95) was significantly higher than in both group I and group II (52.16 +/- 22.8, 57.35 +/- 16.21) (p < 0.001). Mean osteocalcin level (35.13 +/- 2.93) in group I was significantly lower than in group III (40.52 +/- 2.83) (p < 0.05). Serum alkaline phosphatase, PICP and IGF-1 levels were not different between the groups (p > 0.05). There was a significant positive correlation between bone alkaline phosphatase and iPTH (r = 0.80, p < 0.0001). Serum osteocalcin correlated with both bone alkaline phosphatase and iPTH (correlation) coefficients were r = 0.44 and r = 0.51 respectively, p < 0.05). It is concluded that bone alkaline phosphatase and osteoocalcin combined with iPTH level seem to be useful noninvasive markers of bone metabolism in dialysis patients.     

Spectrum of renal osteodystrophy in children on continuous ambulatory peritoneal dialysis

BACKGROUND: The prevalence of different types of bone disease in chronic renal failure (CRF) has changed significantly during the last decade. The aim of the present study is to evaluate the spectrum of bone disease in children with CRF undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Seventeen children with CRF on CAPD aged 7-20 years were evaluated. All patients had received regular vitamin D and calcium carbonate therapy during the 6 months preceding the bone biopsy. Serum calcium, phosphate, alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) levels were measured and hand X-rays were performed. Transiliac bone biopsies were analyzed for histologic diagnosis. RESULTS: High turnover renal osteodystrophy (ROD) was the most common bone disease, present in eight patients (47%). Five patients (29%) had low turnover bone disease, and four (24%) had mixed ROD. The mean age of the high turnover ROD group was higher than that of the low turnover group (14 +/- 3 vs. 11 +/- 3 years, P < 0.05). Seven of the nine patients who had tubulo-interstitial nephritis were found to have high turnover bone disease. In contrast, none of the patients with glomerulonephritis exhibited high turnover bone lesions. Mean serum calcium levels were found to be significantly higher in the low turnover group compared with the patients with high turnover bone disease (P < 0.001). A serum iPTH level > 200 pg/mL was 100% sensitive and 66% specific in identifying patients with high turnover ROD. CONCLUSION: The spectrum of bone disease of the children with CRF undergoing CAPD seems to depend on the rate of CRF and primary disease. The risk of developing overt hyperparathyroid bone disease is high in children with slowly progressing forms of renal pathology and especially in those with tubulo-interstitial disease. In contrast, children with glomerular diseases who had a more rapidly progressive course may have a lesser risk of developing high turnover bone disease. The results of the present study indicate that even routinely prescribed regular vitamin D therapy early in the course of disease may lead to low turnover bone lesion in small children who have CRF due to rapidly progressive forms of renal pathology.     

Chelation therapy and bone metabolism markers in thalassemia major

The aim of our study was to investigate the effects of subcutaneous desferrioxamine (DFX) and oral deferiprone (L1) therapy on bone metabolism markers in patients with thalassemia major. We studied 17 patients with thalassemia receiving long-term treatment with desferrioxamine, 20 patients receiving long-term treatment with deferiprone, and 15 healthy age-matched controls. The following investigations were performed: a) intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] as endocrine parameters; b) alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), osteocalcin (OC); c) bone resorption biochemical markers in serum and urine pyridinium crosslinks: hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP); d) serum levels of cytokines and growth factors: transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-a (TNFalpha); e) serum levels of IGF binding protein-3 (IGFBP-3). No significant differences among all studied variables were found in patients with thalassemia treated with desferrioxamine or deferiprone. In contrast, significant differences were found between patients with thalassemia and the control group: intact PTH was significantly lower in patients with thalassemia than in the controls (p < 0.0005), and a significant increase in ALP and BALP (p < 0.0005), but not in OC, was found in the patient group. With regard to bone resorption and remodeling markers, the urinary excretion of pyridinium crosslinks was higher in patients with thalassemia for HP fraction (p < 0.0005) and LP fraction (p = 0.002), as well as TGFbeta (p = 0.001). In contrast, IGF-I and IGFBP-3 were reduced when compared with controls. In conclusion, the study of bone metabolism markers in adult patients with thalassemia reveals a complex behavior with an increase in bone resorption indexes. Bone formation did not appear to be impaired. In particular, TGFbeta1 was higher in patients with thalassemia receiving L1 treatment.     

Correlation between vascular endothelial growth factor and leptin in children with cyanotic congenital heart disease

The objective in this study was to determine whether there was any relation between leptin and vascular endothelial growth factor (VEGF) in children with cyanotic and acyanotic heart anomalies. The study group consisted of 18 children with cyanotic congenital heart disease (CHD) and 20 age-adjusted children with acyanotic CHD as controls. Serum VEGF and leptin levels were determined by enzyme-linked immunosorbent assay (ELISA). The mean VEGF level was 149.25+/-42.93 pg/ml (range 80.66-217.00) in the cyanotic group and 88.18+/-20.94 pg/ml (range 48.44-112.71) in the acyanotic group (p<0.001). The mean leptin level was 7.55+/-1.46 ng/ml (range 4.08-10.25) in the cyanotic group and 6.89+/-1.43 ng/ml (range 2.67-8.57) in the acyanotic group (p=0.168). There was a significant positive correlation (r=0.723, p<0.001) between VEGF and leptin levels in the cyanotic group while there was no correlation (r=0.235, p=0.348) in the acyanotic group. Arterial oxygen saturation (SaO2) was negatively correlated (r=-0.625, p<0.001) with VEGF, but not correlated with leptin (r=-0.207, p=0.211) in the cyanotic group. There was no correlation between VEGF, leptin and SaO2 in the acyanotic group. We conclude that it is likely that both VEGF and leptin have a role in the pathogenesis of angiogenesis in cyanotic CHD.     

The evaluation of selected parameters of calcium and phosphorus metabolism in children with cow's milk allergy

The aim of this study was to evaluate selected parameters of calcium and phosphorus metabolism in children with CMA treated with the following milk substitute formulas: lactose-containing extensively hydrolyzed wheat protein formula, lactose-free extensively hydrolyzed casein protein formula, as well as soy-based formula. Material and methods: The study involved 66 children with CMA aged 2-5 years treated with milk-free diet for at least one year. Group I included 31 children fed with a lactose-containing formula, group II - 35 children treated with lactose-free formula. In all children the mean energy intake and nutritional value of daily food rations were assessed. Serum concentrations of calcium (Ca), phosphorus (P), sodium (Na) and magnesium (Mg) were determined using standard methods. Serum values of 25 hydroxyvitamin D (25-OH D) and parathormone (PTH) were assessed by chemiluminescence, whereas concentrations of biochemical markers of bone formation-bone alkaline phosphatase (BALP), osteocalcin (OC) and bone resorption marker-collagen type I crosslinked C-telopeptide (CTX) were determined by immunoenzymatic methods (ELISA), using specific monoclonal antibodies. Results: There were no significant differences in the mean dietary supply of calcium, phosphorus, magnesium, sodium, total protein and vitamin C in children from both groups. In the diets of children from group II, the mean content of lactose (0.5±1.0 vs 10.0±6.8 g/d) and 25-OH vitamin D (4.1±2.3 vs 8.5±4.0 ug/d) were significantly lower and dietary fibre content (14.7±3.9 vs 10.4±3.9 g/d) was higher. Calcium and vitamin D dietary supply was lower with respect to nutritional recommendations in all the studied children, whereas the dietary deficiency of vitamin D was higher in children from group II. The mean serum concentrations of evaluated biochemical parameters did not reveal any differences in children from the study groups and were in the normal ranges. There were also no differences in the mean serum concentration of 25-OH vitamin D, ALP, BALP, CTX and PTH in patients from both groups. The mean concentration of OC was significantly higher in group II (71±26.6 ng/ml) than in children from group I (61.1±23.4 ng/ml) <0.01. Positive correlation was found between OC and CTX in both study groups. Conclusions: 1. In children with CMA basic blood laboratory tests may have limited importance in the evaluation of calcium and phosphorus metabolism. 2. Our results suggest that the disturbances in the balance between bone formation and bone resorption processes may occur in children with CMA treated with lactose-free formulas. 3. In order to assure optimal conditions for achieving adequate bone mass by children with CMA, it is necessary to provide them with regular medical and nutritional care.     

Vitamin D supplementation to healthy children does not affect serum osteocalcin or markers of type I collagen turnover

AIM: New serum markers have recently been introduced in the assessment of bone turnover. Such measures are osteocalcin, the C-terminal propeptide of type I procollagen (PICP), the N-terminal propeptide of type I procollagen (PINP) and the C-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP). This study aimed to determine whether supplementation with vitamin D3 to healthy children during the winter affects bone turnover in healthy children measured by serum osteocalcin, PICP, PINP or ICTP. METHODS: 12 girls and 8 boys aged 6.2-13.7 (mean 9.8) y, all proven healthy by medical examination and history, were enrolled in a double-blind, randomized, placebo-controlled, cross-over study with two 4 wk treatment periods and 2 wk washout. Vitamin D3 600 IU was given in one tablet of ABCDin daily. On the last day of the 4 wk periods blood was sampled for assessment of serum osteocalcin, PICP, PINP, ICTP, 25-OH-vitamin D, 1,25-diOH-vitamin D and parathyroid hormone (PTH). RESULTS: During supplementation and placebo periods serum osteocalcin (mean +/- SEM) was 53.9 +/- 5.7 and 54.4 +/- 3.8 microg l(-1) (p = 0.70), PICP was 437+/- 44 and 429 +/- 41 microg l(-1) (p = 0.73), PINP was 579 +/- 56 and 619 +/- 64 microg l(-1) (p = 0.33) and ICTP was 13.4 +/- 0.9 and 13.6 +/- 0.7 microg l(-1) (p = 0.52), respectively. Mean +/- SEM serum 25-OH-vitamin D was 47.0 +/- 2.3 and 33.0 +/- 3.0 nmol l(-1) during vitamin D3 supplementation and placebo (p < 0.001, t = 8.10, 95% CI = 10.3 to 17.6 nmol l(-1)), 1,25-diOH-vitamin D and PTH were 87.5 +/- 4.3 and 92.0 +/- 5.3 pmol l(-1) (p = 0.38), and 3.97 +/- 0.5 and 4.21 +/- 0.4 micromol l(-1) (p = 0.37), respectively. CONCLUSION: Supplementation with 600 IU vitamin D3 to healthy children in the winter does not affect bone turnover as measured by serum osteocalcin, PICP, PINP or ICTP. Vitamin D supplementation to healthy children may not be recommended on the ground of concern for bone turnover.     

Serum prolactin in celiac disease

Serum prolactin levels (SPL) were estimated in patients with celiac disease (CD), diagnosed as per ESPGAN criteria, on unrestricted gluten containing diet (group 1), as well as those consuming a gluten-free diet (GFD) (group 2). Forty-one children with CD, with 20 cases in group 1 (mean age 5.67 +/- 2.14, range 2.5-10.5 years) and 21 cases in group 2 (mean duration of follow-up 2 years, range 1-4 years), and 41 age- and sex-matched controls were studied. Hyperprolactinemia was defined as serum prolactin > 18 ng/ml in males and > 24 ng/ml in females. Upper gastrointestinal endoscopic biopsy was performed in both study groups for initial and follow-up evaluation. Hyperprolactinemia was detected in all the patients of group 1 and one patient of group 2 who had severe villous atrophy. The SPL in group 1 (mean 48.3 +/- 17.4; range 20-90 ng/ml) and group 2 (mean 18.3 +/- 6.9, range 10-39 ng/ml) was significantly higher compared with the controls (mean 9.3 +/- 4.5; range 2.4-20 ng/ml; p < 0.001). Among the patients with CD, mean SPL in group 1 was significantly higher than in group 2 (p < 0.001). In group 1, there was a positive correlation between SPL and duration of symptoms (p = 0.006, r = 0.768) and age of diagnosis (p < 0.001, r = 0.842). A positive correlation also existed in group 2 between SPL and degree of villous atrophy (p < 0.001, r = 0.71) and lamina propria infiltrate (p < 0.001, r = 0.568). Our results suggest that SPL has a significant correlation with activity of CD. Therefore serum prolactin estimation may provide an additional marker of disease activity in CD and may be a more viable option economically.     

Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis

This paper describes a retrospective evaluation of the course of renal bone disease in 14 children undergoing treatment with continuous ambulatory peritoneal dialysis (CAPD) for an average of 11.9 +/- 1.5 months (mean +/- SE). The patients were divided in two groups according to the changes in serum alkaline phosphatase activity during the period of observation: five patients had alkaline phosphatase activity that decreased or was relatively stable (group I), and nine patients exhibited a rising serum alkaline phosphatase activity (group II). Serial radiological examinations showed adequate control of renal osteodystrophy in the patients of group I, whereas the patients of group II had no improvement or worsening of their bone disease. Group I had higher serum calcium and lower parathyroid hormone levels than group II at the end of period of observation despite similar dosage of vitamin D metabolite. The progression of bone disease was not related to the duration of CAPD or type of previous treatment for end stage renal disease. The observation that the radiological manifestations of secondary hyperparathyroidism were prevented in patients whose serum calcium levels were frequently above 2.62 mmol/liter (group I) while serum calcium levels between 2.25 and 2.50 mmol/liter in group II patients failed to lead to regression of secondary hyperparathyroidism is consistent with the existence of altered "set-point" regulation of the parathyroid gland in children undergoing CAPD.     

Leptin levels in children with insulin dependent diabetes mellitus

Leptin, a product of the ob gene, is a polypeptide hormone produced in adipose tissue that informs the brain about the amount of energy storage of body fat. It has very important effects on neuroendocrine functions and energy expenditure. The aim of our study was to determine leptin levels of children with insulin dependent diabetes mellitus (IDDM), which is known to affect body metabolism, and to investigate the relationship between duration of the disease, insulin dosage, HbA1c levels, body mass index (BMI), serum lipids and IGF-1 levels. Sixteen patients with IDDM (chronological age 13.8 +/- 2.6 years) whose HbAlc levels were 10.2 +/- 1.9 %, BMI 21.2. +/- 2.7 kg/m2, insulin dosage 0.9 +/- 0.4 U/kg/day and duration of the disease 6.7 +/- 2.6 years, and 12 healthy controls (13.4 +/- 2.6 years) were included in the study. Fasting plasma leptin levels were measured by radioimmunoassay method. The mean plasma leptin levels of the patient and the control groups were 19.1 +/- 7.6 ng/ml and 6.1 +/- 2.9 ng/ml, respectively, and significant difference was found between the two groups (p < 0.05). No correlation was found between leptin values and IGF-1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, atherogenic index, insulin dosage or HbA1c levels in the patient group. A weak statistical correlation was determined between BMI and leptin levels in the IDDM group (r = 0.28, p < 0.05). A positive correlation was also found between leptin levels and the duration of the disease (r = 49, p < 0.05). As a result, it seems that leptin levels of children with IDDM differed from the levels of the control group significantly, and that the duration of insulin therapy was responsible for this difference.     

Serum osteocalcin concentrations in children with metabolic bone disease

We surveyed both normal children and patient populations to identify the effects of metabolic bone disease and impaired renal function on serum levels of osteocalcin, a vitamin K-dependent protein synthesized in bone. Cord blood osteocalcin was nearly double that of maternal osteocalcin, but there was no correlation between the two. Infants with Apgar scores less than or equal to 7 had a lower mean serum osteocalcin value (8.7 ng/ml, n = 8) than did those with scores of 8 to 10 (16.6 ng/ml, n = 38). Serum osteocalcin elevation coincided with the pubertal growth spurt. In boys, levels decreased to adult values by 18 years of age, as do other indices of bone metabolism; in girls, the levels decreased earlier and had a less pronounced maximum. In children with renal failure, osteocalcin was substantially increased, presumably because of diminished renal clearance of the protein. Children receiving peritoneal dialysis, however, had mean serum concentrations less than half of those seen in children receiving hemodialysis (117 vs 328 ng/ml). The peritoneal dialysate contained significant amounts of osteocalcin, but none was detectable in hemodialysate. Correlation between bone disease and serum osteocalcin was evident in a longitudinal study of one patient with renal failure. Children with various forms of rickets had elevated osteocalcin levels; hypoparathyroidism and osteoporosis were accompanied by variable changes. Serum osteocalcin holds promise as a useful marker of subacute changes in bone metabolism.     

Increased serum IL-2R levels in coeliac disease are related to CD4 but not CD8 antigens.

Forty-three coeliac children, ranging from 1 year and 3 months to 14 years and 9 months, were studied. Twenty-eight patients were in an active phase of the disease, and 15 were in remission. The criteria of coeliac disease (CD) activity were established according to the results of IgA anti-endomysial antibodies (IgA-AEm). Interleukin 2 receptor (IL-2R) and CD4 and CD8 antigens were measured in serum samples by an ELISA technique using two noncompetitive monoclonal antibodies. Antigliadin antibodies of IgG (IgG-AGA) and IgA (IgA-AGA) classes were also measured. The AEm-positive coeliac patient group showed values of 1,860 +/- 948 U/ml for IL-2R, 430 +/- 228 U/ml for CD8, and 36.8 +/- 25.1 U/ml for CD4. AEm-negative patients showed values of 980 +/- 436 U/ml, 350 +/- 243 U/ml, and 24.1 +/- 20 U/ml, respectively. IL-2R levels were the only ones significantly elevated (p < 0.005) in the active coeliac group. On the other hand, IgG-AGA and IgA-AGA were both clearly increased (p < 0.001). IL-2R levels in active coeliac patients correlated with CD4 levels (p < 0.05), but not with CD8, IgG-AGA, and IgA-AGA levels. We also found a surprising negative correlation between AEm antibodies of IgA2 class with both IL-2R (r = 0.471; p < 0.05) and CD8 (r = 0.616; p < 0.05). The results show that in CD there is a lymphocyte activation affecting mainly CD4+ cells and not correlated with serum AGA levels, suggesting an independence of both immunological phenomena and probably with different locations of origin.     

Urinary excretion of cyclic nucleotides and phosphate in response to parathyroid hormone and calcitonin in man

The response to parathyroid hormone (PTH) and calcitonin (CT) was studied in eight children with various bone diseases by determining the serum calcium (Ca) and phosphate (P) concentration, urinary phosphate excretion rate, renal phosphate clearance, the percentage of filtered phosphate reabsorbed by the renal tubule (%TRP), creatinine clearance (Ccr), urinary cyclic adenosine 3',5' monophosphate excretion rate (UcGMPV). Administration of PTH caused no significant change in serum Ca and P values, whereas CT produced a decrease in Ca (delta Ca, -1.4 +/- 0.1 mg/100 ml) and P (delta P; -1.1 +/- 0.1 mg/100 ml). There was an increase in UcAMP V (delta UcAMP; 437 +/- 74 nmoles/min/100 ml Ccr) without any significant change in UcGMPV after administration of PTH. Phosphaturia was produced by both PTH (delta TRP, -18 +/- 3%) and CT (delta TRP, -13 +/- 2%). However, CT did not elicit any increase in either UcAMPV or UcGMPV.     

Aldosterone concentrations in dehydrated infants

The mean serum aldosterone concentration of 37 infants with acute gastroenteritis and dehydration was markedly elevated on admission (mean +/- SE 94.3 +/- 12.1 ng/ml) and approximated to normal values (18.2 +/- 3.7 ng/ml) following recovery from the acute disease (t=3.56 p less than 0.005). Serum aldosterone levels were significantly positively correlated with the percent weight loss (r=0.41, p less than 0.05) and with the blood urea nitrogen levels (r=0.55, p less than 0.001). There was no correlation between either serum sodium levels or blood osmolarity and aldosterone concentrations. Serum potassium levels were positively correlated with aldosterone levels (r=0.53, p less than 0.001). These findings indicate that small infants when dehydrated respond appropriately with elevated aldosterone levels. The amount of body fluid depletion and hyperkalemia are the major factors determining the amount of aldosterone response.