Calcium-phosphate metabolism and bone markers in two patients with Noonan's syndrome treated with growth hormone

AIM: To evaluate the possible effects of recombinant growth hormone (rhGH) therapy on mineral homeostasis and bone turnover, the authors studied calcium-phosphate metabolism parameters, including some bone markers, in 2 prepubertal subjects with Noonan's syndrome (NS). METHODS: Two prepubertal males suffering from NS, short stature (-3.9 and -5.4 SDS respectively) and low growth velocity (3.9 and 3.3 cm/year), were treated with rhGH (0.85 U/kg/week) for 1 year. Serum levels of total calcium (Ca), inorganic phosphate (P), magnesium (Mg), parathyroid hormone (PTH), calcitonin (CT), 25OH vitamin D, 1.25(OH)(2)D, osteocalcin (BGP), type I procollagen carboxy-terminal propeptide (PICP) and its telopeptide (ICTP) were measured. RESULTS: The baseline values were in the normal range; during the treatment no remarkable difference in the values of every one parameters was detected in the 2 patients studied. In one of them, who responded to GH treatment with significantly improved growth velocity, serum levels of the BGP increased during the first semester, and then progressively declined; conversely, serum levels of the ICTP remained stable during the first 6 months of GH-therapy, whereas increased in the following 6 months. CONCLUSION: The results suggest that in Noonan's syndrome patients responding to GH-therapy, a stimulation of bone turnover, with ensuing increase of height velocity, takes place, at least during the first year of GH-therapy. The authors underline the necessity of confirming their results on a larger group of patients with Noonan's syndrome.     

Biochemical markers of bone turnover,intact serum parathyroid hormone and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n=20). The results were compared with subjects with low (hypoparathyroidism, HP, n=29), normal (controls, n=31) and high (primary hyperparathyroidism, 1°HPT, n=13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1°HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1°HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r=–0.69, P<0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment. The urinary calcium excretion remained normal in the patients with PHP but was markedly elevated in patients with HP after the serum calcium levels had normalized during vitamin D therapy. In conclusion, the present and other studies suggest that the resistance to PTH in patients with PHP is mainly limited to the proximal kidney tubule and that the tendency to increased bone degradation implies either some response of the remodelling bone system to PTH or the result of marked secondary hyperparathyroidism overcoming a partial resistance of bone cells. The aim of vitamin D treatment in patients with PHP should therefore be an elevation of the serum calcium concentration into the high normal-range in order to suppress PTH secretion and thus bone degradation. In these patients the parathyroid glands are less sensitive to circulating calcium levels.Abbreviations AHO Albright's hereditary osteodystrophy - AMP adenosine monophosphate - AP alkaline phosphatase activity - Ca calcium - Ca/Cr urinary calcium/creatinine ratio - Cr creatinine - HP hypoparathyroidism - 1°HPT primary hyperparathyroidism - OH-P/Cr urinary hydroxyproline/creatinine ratio - PHP pseudohypoparathyroidism - PTH parathyroid hormone - SDS standard deviation score     

糖皮质激素对肾病综合征患儿骨代谢的影响

目的 探讨糖皮质激素（GC）治疗对肾病综合征（NS）患儿骨代谢的影响。方法选择初发特发性肾病综合征（INS）患儿48例，予以GC治疗，并辅以钙尔奇D片，分别在GC治疗前（活动期）、激素治疗尿蛋白转阴后（缓解期）及肾病持续缓解5个月时（恢复期）检测血清骨钙蛋白（BGP）、骨特异性碱性磷酸酶（BALP）、甲状旁腺素（PTH）和钙水平。以同期儿保科体检的30例健康儿童为对照。结果INS患儿活动期血清BGP、钙水平较对照组明显降低（P〈0．01），血清BALP、FPTH较对照组明显升高（P〈0．01）。缓解期血清BGP最著低于活动期（P〈0．01）；血清BALP较活动期明显下降（P〈0．01），但与对照组比较无显著性差异（P〉0．05）；血清VFH高于活动期（P〈0．05）；血清钙高于对照组（P〈0．01），与活动期无显著性差异（P〉0．05）。NS患儿恢复期血清BGP、BALP、PTH、钙与对照组比较均无显著性差异（P〉0．05）。结论NS本身和GC治疗均可引起患儿骨代谢异常，但只要合理应用激素并及时补充VitD和钙制剂，骨代谢异常可以逆转。     

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.     

Effect of Glucocorticoids on Bone Gla Protein Values -BGP as a Good Marker of Osteoporosis-

It is important to prevent corticosteroid(CS)-induced osteoporosis, particularly in children. One of the mechanisms is a direct inhibitory effect of C S on osteoblasts. Bone Gla protein (BGP) is produced in osteoblasts, and the serum level of BGP reflects the bone formation rate. The aim of this study is to examine the usefulness of BGP as a marker of CS-induced osteoporosis. In the present study, serum levels of 24 pediatric patients who were given prednisolone (PSL) for long periods were studied in relation to their growth rate. Serum BGP was also determined in 167 healthy children and 16 adults. In healthy children, BGP levels reached a peak at the age of 15 years in boys and 11 years in girls. In patients who were given more than 0.25 mg/kg/day PSL, serum BGP levels were significantly decreased and height growth was remarkably suppressed. In conclusion, the measurement of serum BGP is useful for early detection of CS-induced osteoporosis.     

Peritoneal clearance of biochemical markers of bone turnover in children with end stage renal failure on peritoneal dialysis

Renal osteodystrophy is one of the important complications in children with end stage renal disease. Non-invasive tools for evaluation of bone metabolism have been proposed in recent years. The aim of this study was to investigate the markers of metabolic bone disease and peritoneal clearance of these markers in children treated with continuous ambulatory peritoneal dialysis (CAPD). In this study, serum osteocalcin (OC) levels were found significantly higher in patients (107.98 +/- 99.99 ng/ml) than in the healthy control group (41.94 +/- 12.94 ng/ml; p<0.05). Mean peritoneal clearance (Clp) of OC was 0.87 +/- 0.91 ml/min. There was no correlation between serum OC and Clp-osteocalcin. There was a positive correlation between serum phosphorus (P) and OC (r=0.394, p=0.031), alkaline phosphatase (ALP) and OC (r=0.520, p=0.003), and parathyroid hormone (PTH) and OC (r=0.441, p=0.017), whereas no correlation was found between OC and calcium (Ca) and OC and magnesium (Mg). There was also a significant correlation between serum ALP and PTH (r=0.714, p=0.0001). A positive correlation was found between serum PTH and Clp of PTH (r=0.471, p=0.009). In conclusion, Clp-osteocalcin is of no interest as a non-invasive marker of metabolic bone disease in children treated with CAPD. But significant correlation between serum OC and PTH, P, and ALP shows that serum OC could be used as a valuable non-invasive biochemical marker of metabolic bone disease.     

Effects of 12 months rhGH treatment on bone and collagen turnover in children with constitutional growth delay

Serum bone Gla protein (BGP), marker of osteoblast function, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and urinary free deoxypyridinoline (DPD), markers of bone resorption, and the aminoterminal propeptide of type III procollagen (PIIINP), marker of type III collagen turnover, were determined in eight prepubertal children (8 males, age range 7-9.6 yr, Tanner stage I) with constitutional growth delay (CGD), before and after 6-12 months of treatment with rhGH (Saizen, Serono, 0.6 IU/kg/week, s.c.). Serum BGP (mean+/-SD: 15.4+/-1.7 ng/ml), ICTP (9.4+/-1.6 ng/ml) and urinary DPD/creatinine (11.3+/-1.7 nmol/mmol) levels were significantly lower (p<0.02, p<0.0001 and p<0.02, respectively) in children with CGD than in healthy age-matched controls (BGP: 18.9+/-3.6 ng/ml, ICTP: 14.3+/-2.6 ng/ml, DPD: 20.7+/-10.0 nmol/mmol), while PIIINP levels of patients were similar to those recorded in controls (6.3+/-0.7 vs 6.7+/-2.3 ng/ml, respectively). Serum BGP, urinary free DPD/creatinine and PIIINP levels significantly increased after 6 (BGP: 20.9+/-2.1 ng/ml, p<0.0001; DPD/creatinine: 16.3+/-3.6 nmol/mmol, p<0.001; PIIINP: 8.1+/-1.6 ng/ml, p<0.005) and 12 months (BGP: 19.2+/-2.0 ng/ml, p<0.0001; DPD/creatinine: 19.7+/-5.1 nmol/mmol, p<0.001; PIIINP: 8.8+/-1.9 ng/ml, p<0.002) of GH treatment. Serum ICTP levels did not significantly change after 6 months (10.6+/-2.1 ng/ml), while a significant increase (p<0.002) was evident after 12 months of therapy (13.6+/-1.3 ng/ml). Our study shows that BGP, ICTP and DPD/creatinine levels are significantly reduced in children with CGD, thus indicating the presence of low bone turnover in this form of short stature. Since GH treatment is able to reactivate bone remodeling and increase collagen synthesis, it is tempting to speculate that a partial GH-IGF-I defect (i.e. locally at bone level) might be one of the factors involved in determining the biochemical alterations of bone metabolism found in this clinical condition.     

Bone gamma-carboxyglutamic acid containing protein in the perinatal period

We measured bone gamma-carboxyglutamic acid-containing protein (BGP), calcium (Ca), phosphorus (P), and alkaline phosphatase (Al-P) in paired maternal and cord sera, and urinary gamma-carboxyglutamic acid (gamma-Gla) in neonates. The circulating BGP was 41.21 +/- 2.47 ng/ml and 7.44 +/- 0.87 ng/ml in the cord (n = 15) and the maternal (n = 14) sera, respectively. The urinary gamma-Gla in the neonates was 147.68 +/- 10.75 mumol/g creatinine (n = 15). The cord serum BGP was significantly higher than the normal adult level. The maternal serum BGP was at the same level as in other adults. It is conceivable that the fetus may produce BGP during gestation, as the cord serum BGP level was significantly higher than the maternal level and there was no correlation between the cord and maternal serum BGP concentrations. The reason for the elevated circulating BGP level in the cord serum is not known, but increased bone turnover may be a factor. The cord serum BGP may include not only carboxylated but also non-gamma-carboxylated GP because of fetal vitamin K deficiency.     

Evaluation of new markers of bone metabolism in renal osteodystrophy in children

Serum intact parathormone (PTH 1.84) and osteocalcin levels were evaluated as early markers for secondary hyperparathyroidism in a group of pediatric patient treated with chronic hemodialysis. PTH 1.84 levels which were more closely related with alkaline phosphatase levels than PTH 53.84 levels, allowed to identify a group of children without biologic or roentgenographic evidence of hyperparathyroidism and with a normal residual hormone level. PTH 1.84 levels seem to be a reliable indicator of parathormone secretion than conventional assays and may be used as a routine test for monitoring children under chronic hemodialysis. Conversely, the plasma osteocalcin level measured by radioimmunoassay was increased in all studied patients regardless of parathyroid status and seemed to be of little value for monitoring renal osteodystrophia. Lumbar vertebral plate bone density studies disclosed abnormalities of bone mineralization in half the children with renal failure. Dialyzed or non dialyzed. Patients with decreased bone mineralization presented, in most of cases, a history of previous steroid treatment. A group of children with very severe renal failure had increased bone mineralization. The interpretation of this abnormality remains to be determined.     

Bone γ-Carboxyglutamic Acid Containing Protein in the Perinatal Period

ABSTRACT. We measured bone γ-carboxyglutamic acid-containing protein (BGP), calcium (Ca), phosphorus (P), and alkaline phosphatase (Al-P) in paired maternal and cord sera, and urinary γ-carboxyglutamic acid (γ-GIa) in neonates. The circulating BGP was 41.21±2.47 ng/ml and 7.44±0.87 ng/ml in the cord (n=15) and the maternal (n=14) sera, respectively. The urinary γ-GIa in the neonates was 147.68 ± 10.75 μ.mol/g creatinine (n=15). The cord serum BGP was significantly higher than the normal adult level. The maternal serum BGP was at the same level as in other adults. It is conceivable that the fetus may produce BGP during gestation, as the cord serum BGP level was significantly higher than the maternal level and there was no correlation between the cord and maternal serum BGP concentrations. The reason for the elevated circulating BGP level in the cord serum is not known, but increased bone turnover may be a factor. The cord serum BGP may include not only carboxylated but also non-γ-carboxylated BGP because of fetal vitamin K deficiency.     

Mineral Metabolism in Obese Children

ABSTRACT. Blood levels of glucose, insulin (IRI), Calcium (Ca), phosphorus (P), alkaline phosphatase (AP), osteocalcin (OC), parathyroid hormone (PTH), calcitonin (CT), 25-hydroxyvitamin D3 (2SOHD3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and urinary excretion of Ca (Ca/Cr), P (TmP/GFR), hydroxyproline (OH-P/Cr) and cyclic AMP (cAMP/GFR) were determined in 16 obese children, aged 8 to 11 years, on a diet rich in calories and carbohydrates and in 15 controls of the same age. Blood glucose, IRI, Ca, P, PTH and CT were also determined in both groups of subjects, during an oral glucose tolerance test (OGTT). In basal conditions glucose, IRI, AP, OC, PTH, CT and 1,25(OH)2D3 levels were significantly higher, and 2SOHD3 levels lower, in obese children than in controls. Urinary Ca/Cr, TmP/GFR were lower in obese than in non obese children, while OH-P/Cr and cAMP/GFR were higher. Bone mineral content (BMC), measured by photon absorptiometry, and BMC/bone width ratio were lower in obese than in non obese children. During OGTT serum Ca and P decreased and serum PTH and CT increased less in obese than in non obese children. In obese children receiving a diet with high carbohydrate content, an alteration of mineral metabolism occurred, characterized by secondary increase of PTH and 1,25(OH)2D3. Ca decreased and PTH and CT increased less markedly during OGTT.     

Evidence for transient peripheral resistance to parathyroid hormone in premature infants

Serum immunoreactive parathyroid hormone (iPTH), ionized calcium, the urinary cyclic AMP/creatinine ratio (cAMP/Cr) and some indices of bone turnover (alkaline phosphatase (AP), serum osteocalcin, and the urinary total hydroxyproline/creatinine ratio (OH-P/Cr)) were measured in 26 preterm infants during the first 4 weeks of life. Despite of stimulated parathyroid gland activity cAMP/Cr, AP, osteocalcin and OH-P/Cr were low during the first week. Thereafter iPTH decreased, whereas cAMP/Cr, and the indices of bone turnover increased, reaching high-normal values (in comparison to full-term infants) during the second and third week of life. Serum iPTH was negatively correlated to cAMP/Cr in the first week (r = -0.61, p less than 0.01), whereas the relationship became positive during the second (r = 0.47, p less than 0.05) and third (r = 0.54, p less than 0.05) week of life indicating maturation of the renal response to PTH. The study supports the concept that in premature infants a transient pseudohypoparathyroid-like state is present during the first week of life reflecting an immaturity of renal and possibly bone response to PTH. This may be an etiological factor in hypocalcemia of prematurity.     

Evidence for Transient Peripheral Resistance to Parathyroid Hormone in Premature Infants

ABSTRACT. Serum immunoreactive parathyroid hormone (iPTH), ionized calcium, the urinary cyclic AMP/creatinine ratio (cAMP/Cr) and some indices of bone turnover (alkaline phosphatase (AP), serum osteocalcin, and the urinary total hydroxyproline/creatinine ratio (OH-P/Cr)) were measured in 26 preterm infants during the first 4 weeks of life. Despite of stimulated parathyroid gland activity cAMP/Cr, AP, osteocalcin and OH-P/Cr were low during the first week. Thereafter iPTH decreased, whereas cAMP/Cr, and the indices of bone turnover increased, reaching high-normal values (in comparison to full-term infants) during the second and third week of life. Serum iPTH was negatively correlated to cAMP/Cr in the first week ( r =–0.61, p <0.01), whereas the relationship became positive during the second ( r =0.47, p <0.05) and third ( r =0.54, p <0.05) week of life indicating maturation of the renal response to PTH. The study supports the concept that in premature infants a transient pseudohypo-parathyroid-like state is present during the first week of life reflecting an immaturity of renal and possibly bone response to PTH. This may be an etiological factor in hypocalcemia of prematurity.     

Parathormone--25(OH)-vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus

Hamed EA, Abu Faddan NH, Adb Elhafeez HA, Sayed D. Parathormone – 25(OH)‐vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus. Background: Skeletal involvement in patients with type 1 diabetes mellitus (T1DM) has complex pathogenesis and despite numerous researches on this problem, many questions remain unanswered. Objective: This study aimed to assess bone status by measurement parathormone (PTH), 25‐hydroxy vitamin D [25(OH)D] serum levels in children and adolescents with T1DM and its relation to insulin‐like growth factor‐1 (IGF‐1), disease duration, puberty stage, and metabolic control. Patients and methods: This study included 36 children and adolescents with T1DM and 15 apparently healthy controls. Serum levels of 25(OH)D, PTH, IGF‐1 measured using enzyme‐linked immunosorbent assay (ELISA), while glycosylated hemoglobin (HbA1c), calcium (Ca), inorganic phosphorus (PO₄) using autoanalyzer. Bone quality assessed using dual energy X‐ray absorptiometry (DEXA). Results: Diabetic patients showed significant increase in PO₄ and PTH levels, while significant decrease in Ca, IGF‐1, and 25(OH)D serum levels. As much as 52.8% of patients showed reduced 25(OH)D, and 30.65% showed elevated PTH serum levels. In diabetic patients, abnormal bone status (osteopenia‐osteoporosis) found mostly in total body (94.40%) then lumber‐spine (88.90%), ribs (88.90%), pelvis (86.10%), thoracic‐spine (80.60%), arms (80.60%) and legs (77.80%), while head bones showed no abnormalities. Long diabetic duration had negative; meanwhile PTH, onset age, and puberty age had positive impact on bone status. Conclusions: Children and adolescent with T1DM have abnormal bone status mostly in axial skeleton which may be contributed to impairment of formation of 25(OH)D and IGF‐1. Physical activity, calcium and vitamin D supplement seem important in T1DM. Elevated serum PTH level in diabetic patients is not uncommon and its positive correlation with bone status needs further investigations.     

Lowered serum Ca, blood ionized Ca, and unresponsive serum parathyroid hormone with oral glucose ingestion in infants of diabetic mothers

Oral glucose ingestion may lower serum Ca in infants of diabetic mothers (IDMs). Six metabolically stable IDMs were studied following ingestion of 1.7 +/- 0.1 g/kg (mean +/- SE) of glucose over 20 min and serum Ca, Mg, P, blood iCa, serum PTH, and CT were measured at 0, 1/2, 1, and 2 h. Data obtained in IDMs were compared with previously reported findings in 10 normal neonates. In IDMs as in normal neonates, serum Ca, Mg, P declined significantly after oral glucose ingestion. Blood Ca2+ was significantly lower at +1/2 h in IDMs versus normal neonates, and by analysis of covariance, trends in blood Ca2+ were significantly different in IDMs versus normal neonates, (p less than 0.05). Serum PTH concentrations were unaltered in IDMs versus a significant rise in serum PTH noted in normal neonates. The difference between the two groups was significant statistically (p less than 0.05). Baseline serum CT was elevated in both groups and did not change. Thus, in IDMs responses to oral glucose ingestion differs from that seen in normal neonates as follows: blood Ca2+ is lowered in IDMs versus normal neonates, and serum parathyroid hormone (PTH) does not respond to a decline in blood Ca2+ in IDMs, whereas in normal neonates serum PTH rises and blood Ca2+ is maintained. We speculate that relative parathyroid gland unresponsiveness occurs in IDMs, which may result in lowered blood Ca2+ after oral glucose ingestion in these infants.     

Bone mineral density and bone metabolism in children treated for bone sarcomas

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of life.     

Mineral metabolism in obese children

Blood levels of glucose, insulin (IRI), Calcium (Ca), phosphorus (P), alkaline phosphatase (AP), osteocalcin (OC), parathyroid hormone (PTH), calcitonin (CT), 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and urinary excretion of Ca (Ca/Cr), P (TmP/GFR), hydroxyproline (OH-P/Cr) and cyclic AMP (cAMP/GFR) were determined in 16 obese children, aged 8 to 11 years, on a diet rich in calories and carbohydrates and in 15 controls of the same age. Blood glucose, IRI, Ca, P, PTH and CT were also determined in both groups of subjects, during an oral glucose tolerance test (OGTT). In basal conditions glucose, IRI, AP, OC, PTH, CT and 1,25(OH)2D3 levels were significantly higher, and 25OHD3 levels lower, in obese children than in controls. Urinary Ca/Cr, TmP/GFR were lower in obese than in non obese children, while OH-P/Cr and cAMP/GFR were higher. Bone mineral content (BMC), measured by photon absorptiometry, and BMC/bone width ratio were lower in obese than in non obese children. During OGTT serum Ca and P decreased and serum PTH and CT increased less in obese than in non obese children. In obese children receiving a diet with high carbohydrate content, an alteration of mineral metabolism occurred, characterized by secondary increase of PTH and 1,25(OH)2D3. Ca decreased and PTH and CT increased less markedly during OGTT.     

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.     

缺氧性肺动脉高压新生儿血清HIF-1α、ET-1及Ca2+变化及意义

目的：探讨血清缺氧诱导因子-1α（HIF-1α）、内皮素-1（ET-1）及血清钙（Ca2+）水平在新生儿缺氧性肺动脉高压（HPH）中的变化及意义。方法：HPH组75例（轻度29例、中度25例、重度21例）,对照组为非HPH住院新生儿22例,所有新生儿均于生后24 h内行超声心动图测定肺动脉收缩压（PASP）,用ELISA法测定血清HIF-1α、ET-1水平,离子选择电极法测定血清Ca2+浓度。结果：HPH 3组患儿血清HIF-1α及ET-1水平较对照组明显增高（P<0.01）,并随PASP增加而递增,分别和PASP呈正相关(rHIF-1α=0.75, P<0.01;rET-1=0.56, P<0.05);重度HPH患儿血清Ca2+水平明显低于对照组（P<0.05）,HPH患儿血清Ca2+水平与PASP无相关性。结论：HPH新生儿血清HIF-1α、ET-1水平与PASP存在相关性,HIF-1α、ET-1参与了HPH的发生,重度HPH血清Ca2+水平较对照组明显降低,提示血清Ca2+在重度HPH的形成过程中发挥了一定的作用。