Elevated Alkaline Phosphatase in Infants With Parenteral Nutrition–Associated Liver Disease Reflects Bone Rather Than Liver Disease

Background: Elevated serum alkaline phosphatase (ALP) in infants with intestinal failure (IF) can be due to parenteral nutrition–associated liver disease (PNALD) or metabolic bone disease (MBD). The purpose of the study was to determine the utility of serum ALP in the diagnostic criteria for PNALD by measuring tissue‐specific levels in infants with IF and PNALD. Methods: A retrospective review of patient data for 15 infants diagnosed with PNALD between December 2012 and August 2013 was performed. PNALD was defined as the presence of 2 consecutive direct bilirubin (DB) levels >2 mg/dL. Fractionated serum alkaline phosphatase was measured in each patient, while the DB was >2 mg/dL. Parathyroid hormone (PTH), vitamin D₃, calcium, and phosphate levels were recorded where available. Results: In 15 infants with PNALD, elevation in total ALP was due to marked elevations in bone‐specific ALP. The median liver‐specific ALP remained within the normal range. PTH, vitamin D₃, calcium, and phosphate levels were within normal limits. Conclusion: While elevated ALP can reflect biliary stasis, the ALP elevation observed in infants with IF and PNALD is predominantly of bone rather than hepatic origin. An elevated unfractionated ALP in infants with PNALD should therefore raise suspicion of underlying bone disease, rather than being attributed to liver disease alone.     

Update on Calcium and Phosphorus Requirements of Preterm Infants and Recommendations for Enteral Mineral Intake

Background: With current Ca and P recommendations for enteral nutrition, preterm infants, especially VLBW, fail to achieve a bone mineral content (BMC) equivalent to term infants. During the first 3 years, most notably in light at term equivalent age (<−2 Z score) VLBW infants’ BMC does not catch up. In adults born preterm with VLBW or SGA, lower adult bone mass, lower peak bone mass, and higher frequency of osteopenia/osteoporosis have been found, implying an increased risk for future bone fractures. The aim of the present narrative review was to provide recommendation for enteral mineral intake for improving bone mineral accretion. Methods: Current preterm infant mineral recommendations together with fetal and preterm infant physiology of mineral accretion were reviewed to provide recommendations for improving bone mineral accretion. Results: Current Ca and P recommendations systematically underestimate the needs, especially for Ca. Conclusion: Higher enteral fortifier/formula mineral content or individual supplementation is required. Higher general mineral intake (especially Ca) will most likely improve bone mineralization in preterm infants and possibly the long-term bone health. However, the nephrocalcinosis risk may increase in infants with high Ca absorption. Therefore, individual additional enteral Ca and/or P supplementations are recommended to improve current fortifier/formula mineral intake.     

Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease

Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and kidney tissues. Beyond the well-known effects on bone mineralization, the bone ALP (BALP) isoforms (B/I, B1, B1x, and B2) are also involved in the pathogenesis of ectopic calcification. This narrative review summarizes the recent clinical investigations and mechanisms that link ALP and BALP to inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality. The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed. Recent advances in different pharmacological strategies are highlighted, with the potential to modulate the expression of ALP directly and indirectly in CKD–mineral and bone disorder (CKD-MBD), e.g., epigenetic modulation, phosphate binders, calcimimetics, vitamin D, and other anti-fracture treatments. We conclude that the significant evidence for ALP as a pathogenic factor and risk marker in CKD-MBD supports the inclusion of concrete treatment targets for ALP in clinical guidelines. While a target value below 120 U/L is associated with improved survival, further experimental and clinical research should explore interventional strategies with optimal risk–benefit profiles. The future holds great promise for novel drug therapies modulating ALP.     

对肺癌乳腺癌和前列腺癌早期骨转移的诊断研究

目的 探讨早期明确恶性肿瘤骨转移的最佳组合。方法 选择35倒骨良性病变患者作为对照组，102例原发性肺癌、乳腺癌和前列腺癌患者作为实验组。用酶法检测血清碱性磷酸酶（ALP）；用麦胚凝集素法检测血清骨性磷酸酶（B—ALP）；用单光子计算机断层扫描仪（SPECT）进行全身核素骨显像的同时，测定血清ALP、B-ALP结果102例恶性肿瘤骨转移率62．8％，其中单发灶21．8％，多发灶78．2％：实验组和对照组ALP比较，差异有显著意义（P〈0．05），B-ALP比较，差异有极显著意义（P〈0．01）；多发灶骨转移患者ALP、B-ALP浓度明显高于单发灶患者（P〈0．01）；B-ALP〉20U／L时，对恶性肿瘤骨转移有一定的诊断价值。结论 同时测定血清B-ALP有助于明确恶性肿瘤患者核素骨显像异常表现的病变性质，可提高早期骨转移的诊断率和诊断符合率。     

不同年龄段小儿血清骨碱性磷酸酶水平的测定

目的:测定不同年龄段骨碱性磷酸酶的水平,并探讨其变化规律。方法:在儿科门诊查体或因某些感染性疾病如上呼吸道感染、心肌炎、肺炎等原因住院的166例患儿和高中、初中健康检体的学生154例作为研究对象。按照传统分组分别将男女研究对象分为6组,采用ELISA法测定骨碱性磷酸酶及总碱性磷酸酶。结果:在生长发育过程的不同阶段,男孩血清骨碱性磷酸酶的水平不同,6个年龄段分组的血清骨碱性磷酸酶水平有差别(F=6.722,P<0.01)。女孩6个年龄段分组之间的血清骨碱性磷酸酶水平无差别(F=2.089,P=0.071>0.05)。结论:小儿血清骨碱性磷酸酶的浓度变化与年龄有关,监测血清骨碱性磷酸酶的水平变化可以准确地判断小儿各阶段生长发育状况。     

骨碱性磷酸酶对佝偻病早期诊断的临床研究

目的:探讨骨碱性磷酸酶(BALP)在小儿佝偻病早期诊断的临床意义。方法:对101例VitD缺乏性佝偻病患儿进行BALP检测并设立正常对照组,对BALP≥250U/L者,结合临床进行血清Ca、P、ALP和X线比较分析。结果:BALP检测具有敏感、特异、简单、快速、经济等优点。结论:BALP是目前佝偻病早期诊断有价值的实验方法,值得普及和推广。     

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n = 55; approximately 800–1000 IU from combined sources) or monitored therapy (n = 54; with an option of dose modification). 25-hydroxyvitamin D [25(OH)D] concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52 ± 2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p = 0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.     

Influence of Human Milk on Very Preterms’ Gut Microbiota and Alkaline Phosphatase Activity

The FEEDMI Study ({"type":"clinical-trial","attrs":{"text":"NCT03663556","term_id":"NCT03663556"}}NCT03663556) evaluated the influence of infant feeding (mother’s own milk (MOM), donor human milk (DHM) and formula) on the fecal microbiota composition and alkaline phosphatase (ALP) activity in extremely and very preterm infants (≤32 gestational weeks). In this observational study, preterm infants were recruited within the first 24 h after birth. Meconium and fecal samples were collected at four time points (between the 2nd and the 26th postnatal days. Fecal microbiota was analyzed by RT-PCR and by 16S rRNA sequencing. Fecal ALP activity, a proposed specific biomarker of necrotizing enterocolitis (NEC), was evaluated by spectrophotometry at the 26th postnatal day. A total of 389 fecal samples were analyzed from 117 very preterm neonates. Human milk was positively associated with beneficial bacteria, such as Bifidobacterium, Bacteroides ovatus, and Akkermancia muciniphila, as well as bacterial richness. Neonates fed with human milk during the first week of life had increased Bifidobacterium content and fecal ALP activity on the 26th postnatal day. These findings point out the importance of MOM and DHM in the establishment of fecal microbiota on neonates prematurely delivered. Moreover, these results suggest an ALP pathway by which human milk may protect against NEC.     

Total 25(OH)D Concentration Moderates the Association between Caffeine Consumption and the Alkaline Phosphatase Level in Pregnant Women

The evidence as to whether caffeine consumption is beneficial or harmful to human health has been mixed. This study aimed to examine the effect of 25-hydroxyvitamin D (25(OH)D) concentration on the association between caffeine consumption and mineral metabolism in pregnant women. This is a cross-sectional study involving pregnant women at their 25th to 35th gestational week recruited at antenatal clinics in the period of July 2019 to December 2020. Peripheral blood samples were collected to determine their total 25(OH)D, albumin, alkaline phosphatase (ALP), calcium, phosphate, and ferritin level in serum. Questionnaires on demographics and dietary intake were also administered. Among 181 pregnant women recruited (Average age = 32.9 years), 50 (27.6%) of them were found to be vitamin D insufficient (25(OH)D concentration < 75 nmol/L), and 131 (72.4%) were vitamin D sufficient (25(OH)D concentration ≥ 75 nmol/L). Adjusted regression models identified an association between higher caffeine intake and lower ALP level only among vitamin D-sufficient pregnant women (β = −0.24, p = 0.006), but not in those with insufficient vitamin D (β = −0.02, p = 0.912). The findings provide new insights into 25(OH)D concentration as a potential modifier of the health effects of caffeine consumption during pregnancy.     

Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind,Randomized, Placebo-Controlled Trial

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (−0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.     

三种糖皮质激素短期应用对婴幼儿成骨细胞功能的影响

【目的】 比较三种糖皮质激素,氢化可的松、甲基强的松龙、地塞米松短期应用对婴幼儿成骨细胞功能的影响。 【方法】 毛细支气管炎住院治疗的患儿30例,分为氢化可的松组、甲基强的松龙组和地塞米松组。分别给予氢化可的松琥珀酸钠10 mg/(kg·d)、甲基强的松龙3~5 mg/(kg·d)、地塞米松0.25~0.5 mg/(kg·d),均静脉注射,连用5 d。于用药前、用药5 d结束后采集血,检测骨碱性磷酸酶和总碱性磷酸酶。 【结果】 1)氢化可的松组、地塞米松组治疗前后血清骨碱性磷酸酶、总碱性磷酸酶水平差异均无统计学意义(t=0.292,P>0.05)。2)甲基强的松龙组治疗前后血清骨碱性磷酸酶水平分别为(82.15±25.86)和(57.27±17.53) U/L,差异有统计学意义(t=3.947,P＜0.01);血清总碱性磷酸酶水平分别为(149.71±22.22)和(117.00±24.93) U/L,差异有统计学意义(t=3.111,P＜0.05)。3)血清骨碱性磷酸酶和总碱性磷酸酶水平呈高度正相关关系(R=0.703,P<0.01)。 【结论】 短期应用常规剂量甲基强的松龙即对儿童成骨细胞功能产生抑制作用。血清总碱性磷酸酶可以替代骨碱性磷酸酶反映儿童成骨细胞功能变化情况。在保证同样临床效应前提下,相对于甲基强的松龙和地塞米松,以使用氢化可的松为宜。     

儿童骨密度与血清硒、锌、钙、铅及碱性磷酸酶水平的关系:附95例报告

目的探讨儿童骨密度(BMD)降低与血清硒(Se)、锌(Zn)、铁(Fe)、钙(Ca)、铅(Pb)及碱性磷酸酶(ALP)水平的关系。方法采用双能X线骨密度仪检测BMD,石墨炉原子吸收法检测血铅,荧光分光光度法检测血硒,等离子体火焰光谱法(ICP)检测血锌,亚铁嗪比色法检测血清铁,偶氮砷Ⅲ染色法检测血钙,速率法测ALP。结果低BMD组血铅水平明显高于对照组(P<0.01),且达轻度铅中毒水平;而血清硒、铁则明显低于对照组(P<0.05);血锌水平两组间差异无显著性(P>0.05)。低BMD组中血钙及ALP同时增高者占73%,显著高于对照组的11.1%。结论儿童低BMD与高血铅、低血硒、低血清铁有一定关联;而血钙与血ALP同时增高可为早期发现低BMD提供有利诊察线索。     

Effect of fluoride exposure on bone metabolism indicators ALP,BALP, and BGP

Objective  

To analyze the changes in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BALP) activity and changes in osteocalcin (BGP) content following fluoride exposure and, thereby, determine the reference indications of fluoride-induced changes in bone metabolism.     

极低出生体重早产儿血清磷、骨碱性磷酸酶、25-羟基维生素D水平动态变化分析

目的 调查分析极低出生体重早产儿血清磷(P)、骨碱性磷酸酶(BALP)、25-羟基维生素D[25-(OH)D₃]水平动态变化,为临床早产儿代谢性骨病的早期预防提供指导。方法 选择入住烟台山医院新生儿科病房且符合入选标准的110例新生儿为研究对象,其中极低出生体重早产儿60例(病例组),足月产儿50例(对照组),分别于出生后1、4、12周空腹采取静脉血2 ml,测定血清P、BALP、25-(OH)D₃水平,分析骨代谢指标的变化情况。结果 病例组25-(OH)D₃水平增长速度低于对照组;两组血清P水平无明显变化。与对照组比较,病例组出生后1、4、12周血清BALP水平均显著性偏高;出生后第12周25-(OH)D₃水平的差异有统计学意义,其中病例组异常率达26.7%,对照组异常率为0。结论 极低出生体重早产儿(病例组)出生后追赶性生长过程中血清BALP、25-(OH)D₃水平与足月儿(对照组)有明显差异,提示该两项指标检测有助于极低出生体重儿代谢性骨病的早期发现及干预,其中以血清BALP指标敏感性较好。     

Early Nutrition during Hospitalization in Relation to Bone Health in Preterm Infants at Term Age and Six Months Corrected Age

Aim: to evaluate the potential association of macronutrient intake in the first postnatal weeks on bone mineral content (BMC) and bone mineral density (BMD) in extremely and very preterm infants. Methods: fifty-eight extremely and very preterm infants were included. Daily macronutrient intake was calculated in g kg⁻¹ day⁻¹ from birth up to 36 weeks postmenstrual age. A dual-energy X-ray absorptiometry whole body scan was used to assess BMC and BMD in preterm infants at term corrected age (TCA) and six months corrected age (CA). Results: fat intake (g kg⁻¹ day⁻¹) in the first four postnatal weeks was positively associated with BMC and BMD at TCA. At six months CA, protein and fat intake (g kg⁻¹ day⁻¹) in the first weeks of life were both individual predictors for BMD. Fat intake (g kg⁻¹ day⁻¹) in the first four postnatal weeks was significantly associated with BMC at six months CA. Conclusion: the association of macronutrient intake in the first postnatal weeks on BMC or BMD, at TCA and six months CA, suggest that early nutritional intervention immediately after birth and during early infancy is important for bone health in the first months of life.     

Metabolic Bone Disease of Prematurity: Risk Factors and Associated Short-Term Outcomes

Despite the importance of early recognition of metabolic bone disease (MBD) of prematurity, there is still significant variability in screening practices across institutions. We conducted an observational study of infants born at ≤32 weeks of gestation with a birth weight of ≤1500 g (n = 218) to identify clinical factors associated with biochemical indicators of MBD. Bone mineral status was assessed by measuring alkaline phosphatase and phosphate levels between weeks 3 and 5 of life. Two comparisons were performed after classifying infants as either MBD (cases) or non-MBD (controls), and as either high or low risk for MBD, as determined based on the results of MBD screening. In total, 27 infants (12.3%) were classified as cases and 96 (44%) as high-risk. Compared with controls, MBD infants had a significantly lower gestational age and birth weight, and a longer duration of parenteral nutrition and hospital stay. Respiratory outcomes were significantly poorer in high- versus low-risk infants. Multivariate logistic regression showed that birth weight was the only independent risk factor for MBD (odds ratio [OR]/100 g, 0.811; confidence interval [CI95%], 0.656–0.992; p = 0.045) and that birth weight (OR/100 g, 0.853; CI95%, 0.731–0.991; p = 0.039) and red blood cell transfusion (OR, 2.661; CI95%, 1.308–5.467; p = 0.007) were independent risk factors for high risk of MBD. Our findings provide evidence of risk factors for MBD that could help clinicians to individualize perinatal management. The association of red blood cell transfusion with MBD is a novel finding that may be related to iron overload and that merits further study.     

北京地区0～6月龄母乳喂养儿维生素D营养状况及相关骨代谢指标评估

目的 研究北京地区0~6月龄母乳喂养儿的维生素D水平变化及与相关指标BAP、PTH的关系,为今后的婴儿保健工作提供数据支持。方法 选取健康新生儿,生后予规律补充维生素D400 IU/d至6月龄,在0、4、6月龄分别取静脉血检测维生素D及BAP、PTH的水平,评估北京地区母乳喂养儿维生素D的现状及各指标之间的关系。结果 0月龄组婴儿维生素D正常与良好的人数仅占28.8%, 经过规律补充维生素D,4月龄组此比值为82.8%,6月龄组为83%。0月龄组25-(OH)D₃水平与4月龄组呈显著正相关关系(r=0.481,P＜0.01),4月龄组BAP及PTH均与血25-(OH)D₃水平呈负相关关系(r=-0.485和-0.216,P＜0.05)。结论 北京地区新生儿血维生素D水平较低,经过规律补充维生素D大部分婴儿可达正常水平,婴儿出生时25-(OH)D₃储备可能对婴儿早期25-(OH)D₃水平产生一定的影响。     

氟接触人群血清中硬骨素的表达及其与氟性骨损伤的关系

[目的]观察氟接触人群血清中人硬骨素（sclerostin,SOST）的水平,分析其与碱性磷酸酶（alkalinephosphatase,ALP）及氟性骨损伤的相关性,探讨SOST在氟性骨损伤发生中的作用及其机制。[方法]采用问卷调查氟接触人群的一般情况、既往史及现患疾病情况,采集静脉血检测SOST、ALP、血氟等指标,并对其进行前臂正位X线检查,采用SPSS 18.0统计软件对数据进行统计学分析。[结果]高氟组SOST为（4.806±0.525）μg/L,与中氟组和低氟组比较差异有统计学意义（P〈0.01）;高氟组的SOST阳性率为25.0%,与低氟组相比差异有统计学意义（P〈0.05）;损伤组、未损伤组和对照组的SOST分别为（4.870±0.504）μg/L、（5.100±0.627）μg/L和（5.234±0.603）μg/L,损伤组与对照组相比差异有统计学意义（P〈0.05）;高氟区对象血清SOST与ALP之间的线性相关系数为-0.319（P=0.001）;血清SOST与氟性骨损伤密切相关,SOST阳性者患氟性骨损伤的风险是SOST阴性者的2.417倍（P〈0.05）。[结论]氟接触人群SOST明显降低,SOST与ALP活性及氟性骨损伤的发生发展有关,降低的SOST可能参与骨代谢及骨损伤过程,其确切机制有待进一步深入研究。     

Fish Oil–Based Lipid Emulsions in the Treatment of Parenteral Nutrition-Associated Liver Disease: An Ongoing Positive Experience

We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children’s Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1–26). The median time to resolution of cholestasis was 40 d (range 3–158). Compared with infants with mild cholestasis (CB of 2.1–5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates.     

An evaluation of total parenteral nutrition using Vamin and Aminosyn as protein base in critically ill preterm infants

A total of 75 preterm infants with gestation less than 32 wk received total parenteral nutrition (TPN) using Vamin and Aminosyn as protein base lasting more than 20 days. They were monitored for signs of liver dysfunction, cholestatic jaundice, and TPN-induced metabolic bone disease (osteopenia of prematurity). It was observed that severity of TPN-induced cholestasis depends on the duration of TPN and quantity of protein infused. When used as a protein base, Vamin seemed to be superior to Aminosyn. TPN-induced metabolic bone disease was strongly correlated to the duration of TPN. We suggest close monitoring of critically ill preterm infants on TPN for quantity of protein infusate, liver dysfunction, cholestatic jaundice, and TPN-induced metabolic bone disease. Intravenous protein intake should be limited to less than 2.5 g/kg/day in preterm infants with gestation less than 32 wk.