骨钙素与儿童生长发育

骨钙素是成骨细胞分泌的骨蛋白，骨钙素水平与成骨细胞活性成正相关，是一项很好的反映骨形成与骨转化的生化指标。小儿骨生长发育有自身特点，骨钙素水平的改变类似儿童身高生长曲线，可以很好地应用于评价儿童生长发育及监测生长障碍患儿对治疗的反应。     

钙、维生素D缺乏对幼鼠骨生长和成骨细胞功能的影响

目的：探讨钙与维生素D营养缺乏对幼鼠骨骼生长和矿化的影响及机制。方法：建立单纯钙缺乏、维生素D缺乏和钙与维生素D同时缺乏的幼鼠动物模型，追踪其长骨的生长发育，并监测血清Ca,P,25-ODH3,骨碱性磷酸酶（B－ALP）水平及骨矿含量的构成的改变；观察反映骨形成和成骨细胞功能的生化标志－血清骨钙素水平。结果：钙缺乏、维生素D缺乏和两者同时缺乏大鼠的长骨生长发育明显落后于正常大鼠；其胫骨重、骨灰重均显著降低；对骨矿成分的分析显示，除K以外Ca,P,Mg,Na均有不同程度减少；实验组大鼠的血清骨钙素水平随实验期延长呈进行性下降。结论：钙和维生素D缺乏影响成骨细胞的功能，使骨形成和矿化过程受阻，从而导致骨骼生长发育质和量的异常。     

少年儿童血清骨钙素检测及在生长发育中的变化

骨钙素（Ｏｓｔｅｏｃａｌｉｎ，ＢＧＰ）是由成骨细胞合成的非胶原骨蛋白，在骨形成和骨代谢中起激素样调节作用，血中骨钙素测定可直接反映成骨细胞活性及骨的形成情况。近年来许多工作证实骨钙素含量与骨矿物质含量、骨密度测定及骨组织形态计量学检查也呈正相关关系［１］，因此骨钙素含量测定是骨形成的一个特异性生化指标。少年儿童是人体骨骼发育的高峰，各年龄段并非完全一致。为探讨这一时期骨骼发育的特点，我们采取较大样本，并做详细分组，对新疆三个主要民族少年儿童各年龄段血清骨钙素水平进行了动态观察，现将结果报告如下。…     

强化钙和维生素D饮品对儿童骨组织生长发育的影响

目的:探讨补充强化钙和维生素D饮品对儿童骨组织生长发育的影响。方法:选择十堰市某小学一年级、二年级儿童283例,其中男143例,女140例,根据是否行饮品干预分为实验组和对照组,实验组进行强化钙和维生素D饮品干预,对照组不进行强化钙和维生素D饮品干预。结果:饮食干预后实验组男童、女童25-羟基维生素D、骨钙素水平均高于对照组(P<0.05)。饮食干预后实验组男童、女童骨矿物含量、骨面积和骨密度水平均高于对照组(P<0.05)。结论:补充强化钙和维生素D饮品可促进儿童骨组织生长发育,提示儿童生长发育期应供给充足的营养素。     

对长期低钙摄入幼鼠的骨骼的研究——Ⅲ 低钙时幼鼠的骨钙素水平

本文研究低钙摄入、维生素D供给正常时幼鼠血中骨钙素水平,以了解低钙时成骨细胞活性。实验采用60只21～23日Wistar断乳幼鼠,随机分为四组:A组,正常钙与VitD摄X组;B组,中度低钙组;C组,重度低钙组;D组,VitD缺乏组。定期监测血25-(OH)D_3水平。于实验中期(3周),末期(6周)分别处死1/2幼鼠,取血与左股骨标本。测血骨钙素水平,以股骨钙与股骨长计算股骨含钙指数。实验建立低钙与低VitD动物模型。结果发现严重低钙幼鼠股骨生长显著落后,VitD缺乏幼鼠股骨生长与正常组相似。低钙与VitD缺乏幼鼠股骨含钙指数均明显低于正常组,低钙组更严重。低钙组幼鼠血骨钙素水平略高于正常组,VitD缺乏幼鼠血骨钙素有增高趋势;提示低钙时股骨增生的成骨细胞活性低下,VitD缺乏幼鼠骨生长受阻程度不如低钙组明显,推测VitD缺乏与低钙时对成骨细胞的作用机理不同。本文研究证实低钙对生长期骨骼的影响远远超过临床估计。     

实验性氟暴露对成骨细胞成骨功能表达的影响

我国不仅地方性氟病流行区域广 ,患者多 ,工业氟暴露对工人健康的影响也较明显。过量的氟摄入可引起全身骨及其他组织损害[1] 。其异常改变与氟中毒导致骨形成及骨矿化异常有关 ,但其机制尚不清楚。我们拟通过离体ＳＤ大鼠成骨细胞培养 ,研究过量氟对成骨细胞成骨活性的影响 ,从而在细胞学水平了解氟骨症的机制。碱性磷酸酶 (ＡＬＰ)和骨钙素 (ＯＣ)是成熟成骨细胞合成和分泌的两种主要的非胶原蛋白 ,代表成骨细胞活性状态 ,是检测骨形成的指标。因此 ,我们通过成骨细胞ＡＬＰ活力及细胞培养液中ＯＣ水平测定 ,了解氟过量对骨形成过程的影响…     

大鼠缺锌时股骨骺生长板的病理形态学改变

为观察大鼠缺锌时股骨骺生长板的病理形态学改变 ,将 30只Wistar大鼠按体重随机分为 3组 :缺锌组 ,对照组和对喂组 ,每组动物 1 0只。缺锌组和对照组饲料锌含量分别为 3 9和 2 4 7mg kg,对喂组饲对照组饲料 ,饲料摄入量与缺锌组相同。动物喂养 8周后处死 ,在普通光学显微镜下观察大鼠股骨组织病理变化并运用形态计量学方法定量描述 ,测定血清骨钙素和生长激素含量。结果发现缺锌组大鼠股骨骺生长板软骨细胞畸形、数量减少 ,骺端骨小梁纤细、疏松、排列紊乱、髓腔相对扩大 ,骨小梁体积显著减少 ,骨小梁板密度降低 ,骨小梁间隙增大 ,血清骨钙素和生长激素含量减少。提示缺锌一方面通过降低循环中生长激素水平抑制骺软骨细胞增殖分化 ,从而使软骨内骨化障碍 ,骨骼生长迟缓 ;另一方面缺锌抑制成骨细胞活性 ,破坏成骨细胞和破骨细胞之间的动态平衡 ,导致骨骼骨量生成减少 ,骨重塑和骨再建不良 ,骨空间结构紊乱。     

超声骨密度在特发性身材矮小儿童中的诊断价值

目的通过检测特发性身材矮小(ISS)儿童桡骨超声骨密度(QUS)变化,探讨ISS儿童骨骼生长的特点,评价QUS在ISS儿童骨生长发育评价体系中的价值。方法选择ISS儿童110例(ISS组)及正常儿童50例(对照组),分别测定两组儿童的身高、体质量,计算体质指数,检测QUS,同时采用酶联免疫吸附(ELISA)法测定其血清IGF-1、BALP、25-(OH)D3水平。结果 ISS组儿童QUS以及血清IGF-1、BALP、25-(OH) D3水平均明显低于对照姐儿童,差异均有统计学意义(P<0. 01)。QUS与BALP及25-(OH) D3、IGF-1之间呈正相关(P<0. 05)。结论 ISS儿童存在GH-IGF-1轴功能异常,其骨骼生长动力不足,导致以成骨细胞为中心环节的骨骼塑造能力低于正常儿童。QUS与血清BALP、25-(OH) D3可以反映ISS儿童的骨骼生长发育状况,能作为评价生长发育判定的监测指标。     

儿童、青少年骨健康:骨纵向生长、骨塑造和骨再造

生长板是实现骨骼纵向生长的基础。骨塑造完成骨径向生长。儿童、青少年骨塑造和骨再造同时存在;成人只进行骨再造。骨塑造时,骨形成大于骨吸收,二者非偶联;骨再造时,骨形成与骨吸收偶联。骨代谢标志物是反映成骨细胞或破骨细胞功能的标志物。本文从组织器官、细胞、分子三个层面,介绍了骨纵向生长、骨塑造和骨再造等过程。     

铅对儿童骨代谢的影响

【目的】　通过对山西省某铅污染较重矿区儿童血铅水平及骨代谢生化指标的测定 ,探讨血铅对儿童骨代谢的影响。　【方法】　整群抽取 5～ 6岁儿童 12 0名 ,应用石墨炉原子吸收光谱法测定血铅值 ;通过酶联免疫法(ELISA)检测本组儿童血清骨钙素 (OC)、骨碱性磷酸酶 (BALP)及 2 5 (OH)D3 水平。　【结果】　随着血铅水平的增高 ,该组儿童的血清OC和 2 5 (OH)D3 水平呈下降趋势 ,而BALP呈上升趋势。其中Ⅲ级铅中毒儿童血清OC较Ⅰ级铅中毒儿童显著下降 (P <0 .0 1) ,而血清BALP显著增高 (P <0 .0 1) ,且Ⅱ级铅中毒儿童血清BALP较Ⅰ级铅中毒儿童已有显著增高改变 (P <0 .0 1)。另外 ,相关性分析表明本调查组儿童血铅水平与OC和 2 5 (OH )D3 呈负相关而与BALP呈正相关。　【结论】　铅中毒可抑制成骨细胞的活动 ,阻碍生长期儿童骨的正常矿化过程     

Osteocalcin. A biochemical marker of bone turnover during puberty

During bone remodelling, osteocalcin is produced by osteoblasts and its level increases during the events characterized by rapid bone turnover. Osteocalcin is a bone matrix protein, which is specific for bone metabolism and it is not influenced by metabolic bone disorders. Osteocalcin is an important marker of bone turnover in physiological and pathological conditions. Physiologically, serum osteocalcin was increased in children, particularly during the first year of life and during puberty, when evolution of the concentration was related to rapidity of physical growth. Evidence of a correlation with growth rates comes from the observation that serum osteocalcin levels parallel the height velocity curve, with higher values in childhood and during adolescence, that later fall to adult values. There are previous studies reporting that there is age- and sex-dependent change in serum osteocalcin levels in children and adolescents with a pattern resembling height velocity curves for children and serum osteocalcin elevation coincides with the pubertal growth spurt. These findings demonstrate that pubertal development and sex should be taken into account rather than chronological age when serum levels of osteocalcin are evaluated. In most of the studies relationships among osteocalcin and chronological age and bone age, but not pubertal developmental stage (sexual maturation stage) were investigated. The aim of our study was to determine whether osteocalcin is a useful marker for the pubertal growth spurt period. In this study, osteocalcin levels in male adolescents were examined in relation to their sexual maturation stage and age. According to our findings, the follow up of osteocalcin levels in relation to sexual maturation stages could be a new method to determine the phase of the pubertal growth spurt. An increase or decrease in osteocalcin levels on consecutive measurements may indicate the child's entering accelerated or decelerated stages of the growth spurt, respectively. We emphasize that the follow up of adolescent growth is made by determination of the sexual maturation stage, and not by age. Osteocalcin is a highly specific, reliable and useful marker for evaluation of the growth spurt and is not influenced by nonosseous disorders.     

维生素D和骨形态发生蛋白-2水平与生长激素缺乏症儿童成骨细胞功能的相关性研究

目的 研究维生素D及骨形态发生蛋白-2(BMP-2)与生长激素缺乏症(GHD)患儿成骨细胞功能的相关性,以期为矮小症的辅助治疗提供理论依据。方法 收集2012年3月—2013年12月确诊为GHD患儿83例作为病例组,同期随机选取健康儿童40例作为对照组,按年龄及Turner分期分为青春期前组和青春期组。测定其身高、身高标准差得分(HtSDS) 、骨龄等一般指标。用酶联法分别检测并比较病例组及对照组儿童血清25(OH)D₃、BMP-2、骨钙素(OC)、Ⅰ型前胶原氨基端前肽(PINP)水平。用Pearson相关性分析法分析25(OH)D₃、BMP-2与OC、PINP、HtSDS、生长激素(GH)峰值、骨龄与年龄差值的相关性。结果 青春期前GHD组和青春期 GHD组患儿血清25(OH)D₃、BMP-2、OC、PINP均显著低于对照组水平(t=4.282、7.162、3.940、4.832,P＜0.05);经Pearson相关性分析,病例组25(OH)D₃与OC(r=0.481)、PINP(r=0.473)、BMP-2(r=0.324)及GH峰值(r=0.545)存在显著正相关性(P<0.05);BMP-2与OC(r=0.322)、PINP(r=0.415)及GH峰值(r=0.619)存在显著正相关性(P<0.05);25(OH)D₃、BMP-2与HtSDS及骨龄和年龄的差值之间无相关性(P>0.05)。结论 GHD患儿骨形成处于低水平状态。GHD患儿骨形成标志物OC、PINP水平降低与其体内低维生素D、BMP-2水平密切相关。GH的分泌状态影响维生素D、BMP-2的水平。     

Decreased serum osteocalcin level in non-alcoholic and alcoholic chronic liver diseases

Serum level of osteocalcin (OC) is believed to be a specific biochemical parameter of bone formation. Decreased serum OC has been reported in alcohol-intoxicated subjects, in patients with primary biliary cirrhosis and in patients with chronic alcoholic liver disease. The question was, whether lower OC level could be detected in patients with nonalcoholic and non-cholestatic chronic liver disease. The serum OC was measured by RIA developed in our laboratory. Results were compared to age and sex matched controls. Decreased OC level was found in 35 out of 47 (74%) patients with non-alcoholic and non-cholestatic liver disease as chronic persistent hepatitis, chronic active hepatitis, fatty liver and cirrhosis, in 21 out of 26 (80%) patients with alcoholic liver disease and in 8 out of 15 (53%) primary biliary cirrhosis. None of the patients had elevated value. There was no correlation between the decreased OC level and the duration or severity of the liver disease and the laboratory parameters as bilirubin, AST, ALT, alkaline phosphatase, albumin, prothrombin, and serum 25-OH-D3 vitamin level. Decreased OC was found also in the patients without cirrhosis. The possible causes are discussed. Relying upon these findings it is supposed that chronic liver disease by itself can influence the osteoblast activity also by some unknown mechanism.     

The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China

Excessive fluoride intake has been shown to affect dentin and cementum mineralization throughout life. Some studies indicated that a HindIII polymorphism, of osteocalcin (OC) gene, was associated with bone metabolism-related diseases. Therefore, it is possible that the variation in OC genotypes will be associated with dental fluorosis (DF) status and/or serum caciotropic hormone level. A case-control study was conducted among children aged 8–12 years in Henan Province, PR China to investigate the association between dental fluorosis, serum calciotropic hormone level, and polymorphisms in the OC gene. HindIII polymorphism in OC gene was genotyped using the PCR-RFLP procedure. OC and calcitonin (CT) level in serum was detected using radioimmunoassay. No significant difference was observed for OC HindIII genotypes among the cases with dental fluorosis, the controls from endemic fluorosis area (EFA) and the controls from non-endemic fluorosis area (NEFA). A significant negative correlation was observed between serum calcium and OC level. No significant relationship was found between OC HindIII polymorphisms and the level of OC and CT. In conclusion, OC HindIII polymorphisms may not be a useful genetic marker for differential risk of dental fluorosis among children in PR China.     

染料木素对去卵巢大鼠骨代谢标志物和松质骨微结构的作用

目的观察染料木素对去卵巢大鼠骨代谢标志物和松质骨微结构的作用。方法 60只7月龄SD大鼠随机分为去卵巢组、假手术组、染料木素干预组[5mg（/kg·d）],分别在3周和15周处死。取血清测定骨钙素（OC）和耐酒石酸酸性磷酸酶5b（TRACP5b）,分离左胫骨行显微CT扫描,分析松质骨微结构。结果去卵巢第3周,染料木素干预组的血清OC和骨小梁间隔大于假手术组,差异有显著性（P〈0.05）;骨小梁数目小于假手术组;组织骨密度和骨小梁厚度大于去卵巢组（P〈0.05）。第15周,染料木素干预组的血清TRACP5b明显小于假手术组;染料木素干预组及去卵巢组的骨小梁数目均小于假手术组（P〈0.05）,骨小梁间隔则大于假手术组（P〈0.05）。结论染料木素对骨形成在去卵巢早期有促进作用,对骨吸收无明显的抑制作用。     

Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat

The dose-dependent bone-sparing effects of dietary isoflavones (IF) were investigated in adult (7-month-old) Wistar rats. Forty animals were ovariectomised, allocated into four groups of ten rats each, and immediately treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) microg/g body weight per d for 91 d; ten sham-operated (SH) controls received the same diet without added IF. Animals were killed on day 91. Both femoral failure load and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DPD) excretion, a marker of bone resorption, and plasma osteocalcin (OC) levels, a marker of osteoblast activity, were higher in OVX animals than in SH animals. Total femoral and diaphyseal BMD and femoral failure load were similar in IF-treated rats and SH rats. Although metaphyseal BMD in IF40 or IF80 rats was similar to that in SH rats, its value was lower in IF20 rats than in controls. The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was similar to that in SH rats. Day 91 plasma OC concentrations in IF-treated rats were similar to day 45 values, but were decreased in OVX and SH rats. Thus, daily IF consumption prevented ovariectomy-induced bone loss, both by depressing bone resorption and stimulating osteoblast activity. Moreover, as only the highest IF level induced a weak uterotrophic activity, the optimal IF dose which preserves both cancellous and cortical bone, but exhibits no oestrogen-like effects on the uterus, was 40 microg/g body weight per d.     

钙尔奇D联合重组人生长激素对特发性矮身材儿童骨代谢及血清IGF-1、25-(OH)D水平变化的影响研究

目的 探讨钙尔奇D辅助重组人生长激素(rhGH)治疗特发性矮身材(ISS)儿童的疗效及对骨代谢指标、胰岛素样生长因子-1(IGF-1)、25 羟维生素D[25-(OH)D]水平的影响。方法 选取2015年1月-2017年6月本院收治的90例ISS患儿(ISS组),随机分为观察组与对照组,每组45例。另选同期性别、年龄相匹配的健康体检患儿45例作为正常组。对照组采用rhGH治疗,观察组采用rhGH加用钙尔奇D治疗。观察两组患儿治疗前及治疗后6、12个月身高(Ht)、骨龄(BA)、生长速度(GV)、身高均值标准差积分(HtSDS)、BA与生活年龄比值(BA/CA)、血清骨代谢指标[骨钙素(OC)、Ⅰ型前胶原氨基端延长肽(P1NP)]及25-(OH)D水平,并与45例健康正常儿童(正常组)进行比较。结果 ISS组的BA、Ht、GV、HtSDS、BA/CA及血清OC、PICP、IGF-1、25-(OH)D水平均显著低于正常组(P<0.05);治疗6、12个月,观察组的BA、Ht、GV、HtSDS、BA/CA及血清OC、PICP、IGF-1、25-(OH)D水平较治疗前显著提高(P<0.05),对照组的25-(OH)D水平无明显变化(P<0.05),且观察组的Ht、GV、HtSDS、HtSDS、及血清OC、PICP、IGF-1、25-(OH)D水平均显著高于对照组(P<0.05)。结论 ISS患儿存在骨代谢异常及IGF-1、25-(OH)D低水平现象,钙尔奇D辅助治疗可改善患儿的骨代谢状态并提高IGF-1、25-(OH)D水平,从而改善生长状况     

Serum bone marker measurements in bone metabolism disorders associated with inflammatory bowel diseases

Patients with inflammatory bowel disease (IBD) have decreased bone mineral density (BMD), which is usually much more remarkable in patients with Crohn's disease (CD) than those with ulcerative colitis (UC). The aim of the present study was to investigate the usefulness of serum beta-Crosslaps (bCL) and osteocalcin (OC) determinations to assess bone metabolism in patients with IBD. Forty-nine patients with IBD (23 UC, 26 CD) and 46 healthy controls were studied. Serum bCL and OC were measured by Elecsys immunoassay. Compared to controls (0.275 +/- 0.14 ng/ml) the mean bCL concentration was significantly higher in the CD (mean = 0.489 +/- 0.25 ng/ml; p < 0.001) and UC groups (mean = 0.439 +/- 0.3 ng/ml; p < 0.01). The mean OC concentration was significantly higher in the CD group (28.52 +/- 14.75 ng/ml) than in controls (21.42 +/- 7.43 ng/ml) but OC level was not significantly increased in the UC group (24.89 +/- 15.08 ng/ml). There was no significant difference in bCL or OC concentrations between the CD and UC groups. These results indicate that the accelerated bone resorption is not associated with increased bone formation in patients with IBD. These two marker of the bone metabolism could be a good laboratory parameter of bone pathology in patients with IBD, especially in CD.     

重组人生长激素治疗特发性矮身材儿童对骨代谢指标的影响

目的探讨重组人生长激素(rhGH)对特发性矮身材(ISS)儿童骨代谢指标的影响。方法选取2017年4月至2018年4月温州市妇女儿童医院收治的青春发育前期的ISS儿童作为观察组(n=40),另选取同期于儿童保健科体检合格的青春发育期前儿童作为对照组(n=40)。在正常饮食、睡眠基础上给予观察组患儿rhGH注射治疗,持续干预12个月。对观察组治疗前、治疗3月、6月、12月后进行生长发育指标、血糖相关指标、甲状腺功能指标、骨代谢指标进行测量。对照组于体检当日检测以上指标。结果治疗前观察组生长发育指标、骨代谢指标均明显低于对照组。观察组治疗12个月后,身高标准差(HtSDS)、体重、骨龄、生长速率的组内差别具有统计学意义(F值分别为2.730、9.510、6.010、52.250,均P <0.05),且随时间推移呈增高趋势。治疗后骨代谢指标骨源性碱性磷酸酶(BAP)、骨钙素(OC)、血清I型前胶原氨基端前肽(PINP)、胰岛素样生长因子1(IGF-1)、骨密度桡骨远端骨量(SOS)的组内差别均具有统计学意义(F值分别为49.900、10.480、19.760、77.960、3.310,均P <0.05),25-羟基维生素D3[25-(OH)D3]差别无统计学意义(P>0.05)。进一步比较后发现,治疗3个月、6个月、12个月后,BAP、OC、PINP、IGF-1随时间推移呈增高趋势,SOS则呈显著递减趋势。治疗前后观察组血糖相关指标、甲状腺功能指标与对照组比较均无显著差异(P>0.05)。观察组治疗期间出现2例皮肤红肿患儿(5.00%),1例头痛患儿(2.50%),2例空腹胰岛素、空腹血糖受损(5.00%)。结论 rhGH在治疗青春发育前期的ISS患儿中具有促进生长、改善骨代谢指标的作用,且对糖代谢及甲状腺功能无不良影响,具有较好安全性。