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.     

Shift of serum osteocalcin components between cord blood and blood at day 5 of life

Vitamin K deficiency is a relatively common condition in neonates. However, the role of vitamin K in neonatal bone metabolism remains to be determined. Osteocalcin (OC) is the most abundant noncollagenous protein in bone, and is regulated to be gamma-carboxylated by vitamin K. In this study, we measured gamma-carboxylated osteocalcin (Gla-OC) and non- or undercarboxylated osteocalcin (Glu-OC) separately, and examined the effects of vitamin K on osteocalcin metabolism. Eighteen full-term healthy neonates were enrolled in this study. In the cord and d-5 blood samples, the OC levels were determined by three different methods to examine the intact OC by immunoradiometric assay (IRMA), Gla-OC, and Glu-OC. Serum vitamin K fractions, hepaplastin test, and type 1 procollagen carboxyl extension peptide were also determined. Urine samples were also collected from the first voiding and on d 5 to determine urinary pyridinoline, deoxypyridinoline, and gamma-carboxylated glutamic acid. Serum levels of phylloquinone (PK) and menaquinone (MK)-4 increased on d 5 following vitamin K administration and increased intake in breast milk and/or formula. The OC levels determined by IRMA did not change between cord and d-5 blood samples, but the Gla-OC level increased remarkably and Glu-OC reduced to a negligible level. OC in cord blood is mainly Glu-OC, and Glu-OC is replaced with Gla-OC within 5 d of life after vitamin K supplement. The IRMA assay fails to distinguish Gla-OC from Glu-OC and caution is needed to estimate bone turnover with this method in the perinatal period.     

长期应用糖皮质激素对慢性血小板减少性紫癜患儿骨代谢的影响

目的探讨长期应用糖皮质激素对慢性血小板减少性紫癜患儿骨代谢的影响以及钙剂和维生素D的干预作用。方法将36例慢性血小板减少性紫癜患儿随机分为干预组(A)和未干预组(B),给予口服泼尼松1.5mg/(kg·d),4～6周后逐渐减量。疗程超过6月。干预组同时给维生素D330万IU1次口服,口服牡蛎碳酸钙75mg,Bid(牡蛎碳酸钙:每片150mg,东盛科技启东盖天力股份有限公司)。每周3天,共6月。治疗前及应用激素4周后采集患儿静脉血,分别测定I型前胶原羧基末端前肽(PICP),尿脱氧吡啶啉(DPD)和DPD排泄率。结果两组患儿糖皮质激素治疗前血清中PICP的浓度、尿中DPD的排泄率无显著性差异(P>0.05);干预组糖皮质激素治疗后血清中PICP的浓度、尿中DPD的排泄率与治疗前相比差异无统计学意义(P>0.05);未干预组糖皮质激素治疗后血清中PICP的浓度较治疗前明显降低、尿中DPD的排泄率较治疗前明显增高,差异均具有统计学意义(P<0.05)。结论长期应用糖皮质激素对慢性血小板减少性紫癜患儿骨骼代谢有潜在的影响,早期干预可以改善。     

Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy

Oral anticoagulants antagonize vitamin K action and potentially impair the carboxylation of osteocalcin, a protein essential for normal bone matrix formation. In the present study, bone mineral density (BMD) and bone turnover markers were evaluated in 23 children under long-term oral anticoagulant therapy. BMD of the lumbar spine was assessed (Dual Energy x-ray Absorptiometry) and reported as z score. Osteoblast [bone alkaline phosphatase, osteocalcin (Gla-Oc), amino-terminal procollagen 1 extension peptide] and osteoclast (urinary calcium and deoxypyridinoline, serum cross-linked C telopeptide) activity markers were measured. Vitamin D {[25(OH) D], parathormone, calcium, phosphorus, magnesium} and vitamin K status [factors II, VII, IX, X, protein C, protein S, undercarboxylated osteocalcin (Glu-Oc)] were determined. The above parameters were also evaluated in 25 healthy controls. Patients presented with higher levels in Glu-Oc, parathormone, and bone resorption markers, lower levels in bone formation markers and 25(OH) D, whereas 52% of them showed signs of osteopenia (-1>BMD z score>-2.5). Statistical analysis demonstrated that anticoagulant therapy was an independent predictor of alterations in Glu-Oc, Gla-Oc, bone alkaline phosphatase, amino-terminal procollagen 1 extension peptide, and serum cross-linked C telopeptide levels. It seems that long-term use of coumarin derivatives may cause osteopenia in children with the risk of developing osteoporosis later in life.     

Bone turnover in children with vitamin D deficiency rickets before and during treatment

Biochemical markers of bone formation [alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (PICP)] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and cross-linked N-telopeptides of type I collagen (NTX)] were measured in 14 children aged 8.5-10.5 mo with vitamin D deficiency rickets before and longitudinally during vitamin D treatment (3000-4000 IU/daily). Forty-four healthy children aged 8-10.5 mo were enrolled as sex- and age-matched controls. Before treatment, serum levels of alkaline phosphatase, PICP, and ICTP, and urinary excretion values of NTX were significantly higher, and serum osteocalcin levels significantly lower than controls (31.4 +/- 3.5 microkat/L and 9.8 +/- 2.9 microkat/L, p < 0.001; 1025 +/- 89 microg/L and 952 +/- 97.4 microg/L, p < 0.02; 15.6 +/- 2.6 microg/L and 14.2 +/- 1.3 microg/L, p < 0.01; 370.7 +/- 109.4 nmol BCE and 201.8 +/- 69.2 nmol BCE, p < 0.001: 17.6 +/- 9.1 microg/L and 22.5 +/- 7.6 microg/L, p < 0.05, respectively). During treatment, serum alkaline phosphatase levels progressively declined in association with the radiographic healing of the skeletal lesions. Serum levels of osteocalcin, PICP, and ICTP, and urinary excretion values of NTX showed a transient but significant (p < 0.05 to p < 0.001) increase in comparison with baseline values during the first 2-4 wk of treatment, and decreased slowly thereafter. They were within the mean +/- 2 SD of controls before the recovery of the skeletal lesions. CONCLUSIONS: These findings suggest that children with vitamin D deficiency rickets have increased bone turnover before and during the first weeks of treatment. Alkaline phosphatase is a more reliable marker than osteocalcin, PICP, ICTP and NTX for diagnosing and monitoring these patients.     

Collagen peptides in osteogenesis imperfecta, idiopathic juvenile osteoporosis and Ehlers–Danlos syndrome

We evaluated the potential of the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of collagen I (ICTP), and the amino-terminal propeptide of type III procollagen (PIIINP) to differentiate osteogenesis imperfecta (OI) from Ehlers Danlos syndrome (EDS) and idiopathic juvenile osteoporosis (IJO) in paediatric patients. Markedly decreased serum concentrations of PICP were found in type I OI, while in IJO they were much less diminished, and in EDS they were near to normal. In type III and IV OI, the serum PICP level was lowered in prepubertal patients, whereas at puberty it was comparable to that in controls. Serum ICTP and PIIINP levels in patients with OI did not differ significantly from the levels in EDS and IJO. Measurements of scrum PICP levels seem to be useful in discriminating OI from EDS and IJO in prepubertal children. In pubertal children, however, they lose their diagnostic power.     

Bone metabolism markers and ghrelin in boys at different stages of sexual maturity

Aim: To examine the relationship of the markers of bone formation (procollagen type I N-terminal propeptide [PINP]) and bone resorption (type I carboxyterminal telopeptide [ICTP]) with bone mineral content (BMC), bone mineral density (BMD), ghrelin and testosterone in boys during puberty.
Methods: Sixty boys were divided in three groups (20 boys in each) based on the pubertal stage (G1, I; G2–G3, II; G4–G5, III). Fasting PINP, ICTP, ghrelin and testosterone were measured. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD) and BMC were measured by DXA.
Results: PINP and ICTP values peaked at the beginning of puberty (Group II). Ghrelin was lower in Groups II and III compared to less mature boys. PINP and ICTP correlated with each other and were associated with lumbar BMAD in total group of boys. Relationships of PINP and ICTP with total BMD, total BMC and lumbar spine BMD in Group I were observed. PINP and ICTP were also correlated with testosterone in Group II and with lumbar spine BMAD in Group III.
Conclusion: These data suggest that testosterone stimulates PINP and ICTP in early puberty, while ghrelin has no direct influence on bone turnover markers in boys at different stages of puberty.     

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.     

Bone mass density and associated factors in cystic fibrosis patients of young age

Aim: To investigate bone mineral status in young cystic fibrosis (CF) patients and determine risk factors related with the development of low bone mineral density (BMD). Methods: We determined, in 81 patients with CF, 4 to 23‐years‐old, BMD as well as factors, which are thought to play a role in the development of reduced BMD. Results: BMD Z‐score was between ?1 and ?2.5 in 27 (33%) and lower than ?2.5 in 9 (11%). Means of BMD Z‐score were lower than the expected value of 0 in the three groups of children, adolescents and young adults (P = 0.004; P < 0.001; P = 0.048, respectively), but they did not differ among them (P = 0.114). Analysis showed that Shwachman–Kulczycki (SK) score, gender and levels of 25‐hydroxy‐vitamin D were significant predictors of BMD Z‐score. Significant also was the interaction between gender and SK score. Conclusions: Our study supports that BMD may be reduced from a young age in CF patients though this needs to be confirmed using true volumetric measures of BMD. This defect is related to disease severity with males being more vulnerable. Inefficient levels of vitamin D are very common and contribute significantly to impaired bone health. The latter finding underlines the need for higher supplementation doses.     

Bone mass, biochemical markers and growth in children with chronic kidney disease: a 1-year prospective study

AIM: This study was designed to investigate bone mineral density (BMD), growth parameters and biochemical markers in children with chronic kidney disease (CKD). METHODS: Sixteen patients, 4-18 years, with CKD were prospectively followed for 1 year. Auxological data, body composition, BMD by dual-energy X-ray absorptiometry, bone age, bone turnover markers, vitamin D, parathyroid hormone (PTH), leptin, osteoprotegerin, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were measured. A questionnaire regarding bone health and diet was also performed. RESULTS: Delayed bone age was observed (n = 11) and the BMD Z-scores for total body were below zero in seven patients. However, total body BMD (TBBMD) increased in 12 patients. Most patients had increased osteocalcin and carboxy-terminal telopeptide of type I collagen, but normal alkaline phosphatase, type I procollagen intact amino-terminal propeptide and tartrate-resistant acid phosphatase 5b. Ten patients had increased PTH. Most children had normal levels of leptin, osteoprotegerin, IGF-I and IGFBP-3. Leptin, at baseline, correlated with differences in TBBMD over 1 year. CONCLUSIONS: Only seven (44%) had negative Z-scores and TBBMD increased over 1 year. Bone markers at baseline did not predict the longitudinal changes in BMD.     

Hypophosphatasia in a child with widened anterior fontanelle: lessons learned from late diagnosis and incorrect treatment

Hypophosphatasia is characterized by deficiency of serum alkaline phosphatase with defective bone and teeth mineralization. We report on an 11‐month‐old boy who developed a complex clinical picture characterized by bulging anterior fontanelle, growth failure, nephrocalcinosis and impaired bone mineralization during high‐dose calcium and vitamin D supplementation. This therapy had been started 5 months earlier for a presumed diagnosis of nutritional rickets established on the grounds of isolated widened anterior fontanelle. However, laboratory investigations revealed reduced alkaline phosphatase levels associated with hypercalcemia, hypercalciuria, low PTH and normal 25‐hydroxy vitamin D levels. Genetic testing detected a compound heterozygote for the novel mutation (c.262G>A) and the described mutation (c.920C>T) in the ALPL gene. Conclusion: High calcium and vitamin D supplementation should not be started in the presence of isolated signs of nutritional rickets without assessing calcium‐phosphate metabolism. In fact, in rare bone‐mineralizing disorders, this combined therapy might induce severe clinical complications.     

Serum procollagen I carboxyterminal propeptide (PICP) levels through puberty: relation to height velocity and serum hormone levels

The synthesis of type I collagen, the major component of the organic bone matrix, is reflected by procollagen I carboxyterminal propeptide (PICP) levels. Conflicting reports have been made about the relationship between PICP levels and puberty. We have studied PICP levels in serum in relation to pubertal stage, height velocity, oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, insulin-like growth factor I and growth hormone levels in 32 healthy boys aged 7.2–15.8 years and 32 healthy girls aged 7.2–14.8 years. The PICP levels in girls tended to be higher during midpuberty; in boys the levels were higher at the end of puberty. The PICP levels correlated strongly with height velocity in boys and girls. In conclusion, PICP correlates especially with height velocity. The variation of PICP between subjects during puberty is considerable. The PICP levels may predict growth at a certain moment, especially in cases where only one height measurement is available.     

1 732例儿童血清维生素K2临床分析及其与骨代谢标志物关系的研究

目的 分析儿童血清维生素K₂（vitamin K₂,VitK₂）临床特征及其与骨钙素（osteocalcin,OC）、Ⅰ型前胶原氨基端前肽（type Ⅰ procollagen amino-terminal peptide,PINP）、Ⅰ型胶原交联羧基末端肽（type Ⅰ collagen carboxy-terminal peptide,CTX）的相关性。 方法 前瞻性选取2020年10月至2021年10月门诊常规体检儿童1 732例,测定血清VitK₂、25羟维生素D［25-hydroxyvitamin D,25(OH)D］水平,按年龄段分为<1岁组、1~3岁组、>3~6岁组、>6~14岁组,进行血清VitK₂相关临床分析。筛选出25(OH)D≥50 nmol/L的儿童共309例,测定血清OC、PINP、CTX水平,分析不同年龄段水平及其与血清VitK₂的相关性。 结果 血清VitK₂缺乏率为52.31%（906/1 732）。VitK₂缺乏组超重/肥胖、生长痛（≥3岁）发生率均高于VitK₂正常组（P<0.05）;1~3岁组和>6~14岁组血清VitK₂缺乏率（P<0.0083）、血清VitK₂水平（P<0.05）差异有统计学意义。<1岁组儿童血清CTX水平高于>3~6岁组和>6~14岁组,而<1岁组儿童血清PINP水平低于>3~6岁组和>6~14岁组（P<0.05）;<1岁组血清OC水平低于>6~14岁组（P<0.05）。血清VitK₂与OC呈正相关（r_s=0.347,P<0.01）,CTX与PINP呈负相关（r_s=-0.317,P<0.01）。 结论 VitK₂缺乏可能与超重/肥胖有关;血清VitK₂可影响OC水平进而影响骨骼健康。     

Serum levels of carboxyterminal propeptide of type I procollagen in healthy children from 1 st year of life to adulthood and in metabolic bone diseases

Type I collagen is the major component of bone matrix; circulating carboxyterminal propeptide of type I procollagen (P-I-CP) levels reflect type I collagen synthesis in tissues and may be an useful index to investigate bone metabolism. We measured P-I-CP by a new radioimmunoassay in 300 healthy children and adolescents and in 40 healthy adults to provide reference data for P-I-CP values. In addition, 79 patients with diagnosed disorders of phospho-calcium metabolism (rickets, vitamin D deficient and vitamin D resistant, hyperparathyroidism, hypo- and pseudo-hypoparathyroidism, osteopenia) were evaluated. In the healthy subjects, serum P-I-CP values were higher in children than in adults; variations of P-I-CP levels were observed according to age and sexual maturation: higher values were found in the first years of life and during pubertal development; pubertal increase reflects the different timing of pubertal development in the two sexes. P-I-CP levels were increased in primary hyperparathyroidism and reduced in diseases related to impaired secretion or action of parathyroid hormone. Higher P-I-CP levels were found in vitamin D deficient and vitamin D resistant rickets. P-I-CP was reduced in anorexia nervosa and during chronic glucocorticoid treatment while it was increased in thyrotoxic osteoporosis. In idiopathic juvenile osteoporosis, P-I-CP values ranged from reduced to increased values. We conclude that P-I-CP may represent an additional biochemical marker of bone metabolism. Since age-related variations are present, reference data for the various ages are need for clinical application of this assay.     

Deficiency of vitamins E and A in cystic fibrosis is independent of pancreatic function and current enzyme and vitamin supplementation

Abstract The aim of this study was to evaluate to what extent serum vitamins A and E in cystic fibrosis are affected by the underlying disease, pancreatic sufficiency or insufficiency, meconium ileus, nutritional status, age and treatment (enzyme and vitamin supplementation). Serum vitamin A and E levels were determined by high performance liquid chromatography in 210 cystic fibrosis patients, subdivided according to clinical condition into four subgroups (unsupplemented pancreatic insufficiency, supplemented meconium ileus, pancreatic sufficiency, supplemented pancreatic insufficiency) and compared with 42 control subjects. Vitamin A and E levels were generally lower in cystic fibrosis patients than in controls (P<0.002 andP<0.001 respectively). Subjects with pancreatic insufficiency regularly receiving enzyme and vitamin supplementation had significantly lower vitamin A (P<0.05) and vitamin E (P<0.01) levels than controls. In subjects with pancreatic sufficiency only vitamin A was significantly lower than in controls (P<0.01). Vitamin levels were not age-dependent in cystic fibrosis, and no significant correlation with standardized body weight (Z-score) was observed.Conclusion Cystic fibrosis patients show a clear tendency to vitamin A and E deficiency, irrespective of pancreatic function, body weight and standardized supplementation with pancreatic extract and liposoluble vitamins. Since the clinical significance of this deficiency is still not clear, longitudinal studies of cystic fibrosis patients with and without adequate vitamin supplementation are required.     

Collagen-derived markers of bone metabolism in osteogenesis imperfecta

Markers of bone formation [C-terminal and N-terminal propeptides of procollagen I (PICP, PINP), osteocalcin and alkaline phosphatase] and bone resorption [C-terminal cross-linked telopeptide of collagen I (ICTP) and hydroxypyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low, and the serum levels were lower in all children and adults with mild OI and a quantitative collagen defect than in patients with severe OI and a qualitative collagen I defect. ICTP, Pyr and Dpyr were generally normal or reduced, but elevated in severely affected adults with a qualitative collagen I defect. The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI.     

Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus

We recently demonstrated that children with type 1 diabetes mellitus (DM) have decreased lumbar spine bone mineral density (BMD) as early as four years after clinical diagnosis of the disease. In order to determine whether osteopenia is already present in patients very early on after diagnosis of clinical DM, we evaluated the bone mineral status of a group of newly diagnosed children (5.8 +/- 1.5 mo after diagnosis). We studied 23 prepubertal children (7 M, 16 F) with a mean chronological age of 9.5 +/- 2.2 yr and a mean glycosylated hemoglobin of 8.9 +/- 2.4%. Lumbar spine and femoral neck BMD were measured by dual X-ray absorptiometry, while bone turnover was assessed by the determination of the serum concentration of the carboxy-terminal propeptide of type I collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type I collagen (N-telopeptide). Results were compared to those of age, height, and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in patients compared to controls (Z-scores of -0.89 +/- 1.2, with 10 of 22 patients showing values >1 SD below the mean). When lumbar spine Z-scores were analyzed in those patients with <3 months or > or =3 months since diagnosis of DM a significant difference was noticed between groups (-0.648 +/- 1.12 vs -1.267 +/- 1.17; p <0.02). No significant differences were noted in femoral neck BMD and total BMD between groups. Serum PICP levels were decreased when compared to controls (233.6 +/- 39.3 vs 375.9 +/- 50.7 microg/l; p <0.002), while serum N-telopeptide concentrations, although increased, were not significantly different (9.3 +/- 1.3 vs 5.7 +/- 1.5 microg/l). In summary, early on after the diagnosis of type 1 DM, children present with decreased lumbar spine BMD and decreased bone formation markers.     

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.     

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。     

The effect of formula versus breast feeding and exogenous vitamin K1 supplementation on circulating levels of vitamin K1 and vitamin K-dependent clotting factors in newborns

The influence of breast or formula feeding together with that of a single supplementation of vitamin K₁ at birth, on the vitamin K₁ level and vitamin K-dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n=25) had very low serum vitamin K₁ at weeks 1 and 6. Oral vitamin K supplementation (n=22) or i.m. (n=18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K₁ values within the normal adult range at all study points. The low serum levels of vitamin K₁ were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K₁ in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K₁ within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age.