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Bone Mineralization and Calcium Phosphorus Metabolism

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 21470

Special Issue Editors

Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain
Interests: nutrition; inborn errors of metabolism; neonatology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The accretion of an adequate mineral content is essential for normal bone mineralization. Mineral homeostasis requires a specific balance of parathyroid hormone, calcitonin, FGF23, and vitamin D activity on target organs (kidney, intestine, and bone). Dietary deficiencies, particularly during pediatric growth stages, and some diseases can increase the risk of mineral imbalance and the development of metabolic bone disease. However, the significant impacts of intake in the prevention of deficiencies under certain conditions, such as prematurity and metabolic disorders, is not well known. In addition, it is very important to identify infants and children at risk of deficiencies in order to prevent or treat mineral homeostasis alterations.

The objectives of this Special Issue of Nutrients are as follows:

  1. To explore the relationship between bone mineralization and nutritional status in children and to identify the best biomarkers for mild alterations.
  2. The majority of bone formation and mineralization occurs late in gestation. The accretion of adequate minerals is often interrupted in preterm birth. Thus, we aim to address how to improve the nutritional intake of minerals in premature infants.
  3. To discuss how alterations in calcium phosphorus metabolism can be identified, prevented, and treated.

Prof. María Luz Couce
Dr. Miguel Saenz de Pipaón
Guest Editors

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Keywords

  • FGF23
  • metabolic bone disease
  • mineral imbalance
  • mineral requirements
  • parathyroid hormone
  • renal tubular function

Published Papers (7 papers)

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Editorial

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3 pages, 213 KiB  
Editorial
Bone Mineralization and Calcium Phosphorus Metabolism
by María Luz Couce and Miguel Saenz de Pipaon
Nutrients 2021, 13(11), 3692; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13113692 - 21 Oct 2021
Cited by 5 | Viewed by 2238
Abstract
The accretion of adequate mineral content is essential for normal bone mineralization [...] Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)

Research

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16 pages, 511 KiB  
Article
Evaluation of Body Composition, Physical Activity, and Food Intake in Patients with Inborn Errors of Intermediary Metabolism
by María-José de Castro, Paula Sánchez-Pintos, Nisreem Abdelaziz-Salem, Rosaura Leis and María L. Couce
Nutrients 2021, 13(6), 2111; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13062111 - 20 Jun 2021
Cited by 6 | Viewed by 2760
Abstract
Children with inborn errors of intermediary metabolism (IEiM) must follow special diets that restrict their intake of essential nutrients and may compromise normal growth and development. We evaluated body composition, bone mineral density, physical activity, and food intake in IEiM patients undergoing dietary [...] Read more.
Children with inborn errors of intermediary metabolism (IEiM) must follow special diets that restrict their intake of essential nutrients and may compromise normal growth and development. We evaluated body composition, bone mineral density, physical activity, and food intake in IEiM patients undergoing dietary treatment. IEiM patients (n = 99) aged 5–19 years and healthy age- and sex-matched controls (n = 98) were recruited and underwent dual-energy X-ray absorptiometry to evaluate anthropometric characteristics and body composition. Data on food intake and physical activity were also collected using validated questionnaires. The height z-score was significantly lower in IEiM patients than controls (−0.28 vs. 0.15; p = 0.008), particularly in those with carbohydrate and amino acid metabolism disorders. Significant differences in adiposity were observed between patients and controls for the waist circumference z-score (−0.08 vs. −0.58; p = 0.005), but not the body mass index z-score (0.56 vs. 0.42; p = 0.279). IEiM patients had a significantly lower total bone mineral density (BMD) than controls (0.89 vs. 1.6; p = 0.001) and a higher risk of osteopenia (z-score < −2, 33.3% vs. 20.4%) and osteoporosis (z-score < −2.5, 7.1% vs. 0%), but none presented fractures. There was a significant positive correlation between natural protein intake and BMD. Our results indicate that patients with IEiM undergoing dietary treatment, especially those with amino acid and carbohydrate metabolism disorders, present alterations in body composition, including a reduced height, a tendency towards overweight and obesity, and a reduced BMD. Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)
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20 pages, 1163 KiB  
Article
Bone Mineral Density, Body Composition, and Metabolic Health of Very Low Birth Weight Infants Fed in Hospital Following Current Macronutrient Recommendations during the First 3 Years of Life
by Walter Mihatsch, Izaskun Dorronsoro Martín, Vicente Barrios-Sabador, María L. Couce, Gabriel Á. Martos-Moreno, Jesús Argente, José Quero and Miguel Saenz de Pipaon
Nutrients 2021, 13(3), 1005; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13031005 - 20 Mar 2021
Cited by 6 | Viewed by 2637
Abstract
The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, [...] Read more.
The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required. Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)
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15 pages, 1142 KiB  
Article
Modified Serum ALP Values and Timing of Apparition of Knee Epiphyseal Ossification Centers in Preterm Infants with Cholestasis and Risk of Concomitant Metabolic Bone Disease of Prematurity
by Sandra Llorente-Pelayo, Pablo Docio, Bernardo A. Lavín-Gómez, María T. García-Unzueta, Isabel de las Cuevas, Luis de la Rubia, María J. Cabero-Pérez and Domingo González-Lamuño
Nutrients 2020, 12(12), 3854; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12123854 - 17 Dec 2020
Cited by 9 | Viewed by 2197
Abstract
The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP [...] Read more.
The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns <32 weeks. A significant correlation existed between serum ALP and direct bilirubin (DB), expressed by the regression equation: M-ALP (IU/L) = 302.1 + 96.9 (DB (mg/dL)). The ratio ALP/M-ALP > 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis. Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)
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13 pages, 1528 KiB  
Article
Metabolic Bone Disease of Prematurity: Risk Factors and Associated Short-Term Outcomes
by Alejandro Avila-Alvarez, Adela Urisarri, Jesús Fuentes-Carballal, Natalia Mandiá, Andrea Sucasas-Alonso and María L. Couce
Nutrients 2020, 12(12), 3786; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12123786 - 10 Dec 2020
Cited by 17 | Viewed by 3632
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)
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Review

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10 pages, 735 KiB  
Review
Update on Calcium and Phosphorus Requirements of Preterm Infants and Recommendations for Enteral Mineral Intake
by Walter Mihatsch, Ulrich Thome and Miguel Saenz de Pipaon
Nutrients 2021, 13(5), 1470; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13051470 - 27 Apr 2021
Cited by 12 | Viewed by 3610
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)
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15 pages, 638 KiB  
Review
Bone Status in Patients with Phenylketonuria: A Systematic Review
by María José de Castro, Carmela de Lamas, Paula Sánchez-Pintos, Domingo González-Lamuño and María Luz Couce
Nutrients 2020, 12(7), 2154; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12072154 - 20 Jul 2020
Cited by 23 | Viewed by 3508
Abstract
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in preventing intellectual disability in PKU patients who are treated early, suboptimal outcomes have been reported, including bone mineral disease. [...] Read more.
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in preventing intellectual disability in PKU patients who are treated early, suboptimal outcomes have been reported, including bone mineral disease. In this systematic review, we summarize the available evidence on bone health in PKU patients, including data on bone mineral density (BMD) and bone turnover marker data. Data from cohort and cross-sectional studies of children and adults (up to 40 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, quality assessment was performed applying the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS I) tool. We found that mean BMD was lower in PKU patients than in reference groups, but was within the normal range in most patients when expressed as Z-score values. Furthermore, data revealed a trend towards an imbalance between bone formation and bone resorption, favoring bone removal. Data on serum levels of minerals and hormones involved in bone metabolism were very heterogeneous, and the analyses were inconclusive. Clinical trials that include the analysis of fracture rates, especially in older patients, are needed to gather more evidence on the clinical implications of lower BMD in PKU patients. Full article
(This article belongs to the Special Issue Bone Mineralization and Calcium Phosphorus Metabolism)
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