Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

2014 ◽  
Vol 94 (4) ◽  
pp. 1143-1218 ◽  
Author(s):  
Christopher S. Kovacs
Keyword(s):  
Serum Calcium ◽  
Calcium Absorption ◽  
Bone Development ◽  
Fibroblast Growth Factor 23 ◽  
Calcium Content ◽  
Maternal Circulation ◽  
Fetal Circulation ◽  
Mineral Homeostasis ◽  
Low Concentrations ◽  
Calcium Phosphorus

Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24–48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium.

scholarly journals Race, Mineral Homeostasis and Mortality in Patients with End-Stage Renal Disease on Dialysis

2015 ◽  
Vol 42 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Julia J. Scialla ◽  
Rulan S. Parekh ◽  
Joseph A. Eustace ◽  
Brad C. Astor ◽  
Laura Plantinga ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
African American ◽  
African Americans ◽  
Serum Calcium ◽  
Mortality Risk ◽  
Fibroblast Growth Factor 23 ◽  
Total Alkaline Phosphatase ◽  
Mineral Homeostasis ◽  
Calcium Phosphorus ◽  
Total Alkaline

Background: Abnormalities in mineral homeostasis are ubiquitous in patients on dialysis, and influenced by race. In this study, we determine the race-specific relationship between mineral parameters and mortality in patients initiating hemodialysis. Methods: We measured the levels of fibroblast growth factor 23 (FGF23) and 25-hydroxyvitamin D (25 D) in 184 African American and 327 non-African American hemodialysis patients who enrolled between 1995 and 1998 in the Choices for Healthy Outcomes in Caring for ESRD Study. Serum calcium, phosphorus, parathyroid hormone (PTH) and total alkaline phosphatase levels were averaged from clinical measurements during the first 4.5 months of dialysis. We evaluated the associated prospective risk of mortality using multivariable Cox proportional hazards models stratified by race. Results: PTH and total alkaline phosphatase levels were higher, whereas calcium, phosphorus, FGF23 and 25 D levels were lower in African Americans compared to those of non-African Americans. Higher serum phosphorus and FGF23 levels were associated with greater mortality risk overall; however, phosphorus was only associated with risk among African Americans (HR 5.38, 95% CI 2.14-13.55 for quartile 4 vs. 1), but not among non-African Americans (p-interaction = 0.04). FGF23 was associated with mortality in both groups, but more strongly in African Americans (HR 3.91, 95% CI 1.74-8.82 for quartiles 4 vs. 1; p-interaction = 0.09). Serum calcium, PTH, and 25 D levels were not consistently associated with mortality. The lowest and highest quartiles of total alkaline phosphatase were associated with higher mortality risk, but this did not differ by race (p-interaction = 0.97). Conclusions: Aberrant phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk factor for mortality in patients initiating hemodialysis, particularly among African Americans.

scholarly journals Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

2013 ◽  
Vol 304 (3) ◽  
pp. E310-E320 ◽  
Author(s):  
Stephen J. Quinn ◽  
Alex R. B. Thomsen ◽  
Jian L. Pang ◽  
Lakshmi Kantham ◽  
Hans Bräuner-Osborne ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Fibroblast Growth Factor 23 ◽  
Threshold Level ◽  
Serum Levels ◽  
Serum Phosphorus ◽  
Dihydroxyvitamin D ◽  
Dietary Phosphorus ◽  
Calcium Phosphorus ◽  
Calcium And Phosphorus

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range.

scholarly journals Phosvitin phosphopeptide preparation using immobilised trypsin and enhancing calcium absorption in growing rats

2016 ◽  
Vol 34 (No. 4) ◽  
pp. 325-331 ◽  
Author(s):  
Q. Zhong ◽  
X. Li ◽  
W. Hu ◽  
B. Zeng ◽  
R. Liang ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Efficient Method ◽  
Calcium Binding ◽  
Calcium Absorption ◽  
Covalent Binding ◽  
Calcium Content ◽  
Egg Yolk ◽  
Calcium Supplement ◽  
Growing Rats

We demonstrate a new, efficient method for the preparation of phosvitin phosphopeptides using immobilised-trypsin enzymolysis technology. Immobilised trypsin was prepared using a covalent binding method, and then was added to degrade egg yolk phosvitin for the production of phosphopeptides. In our results, the prepared immobilised trypsin demonstrated a higher hydrolysing activity toward phosvitin than free trypsin, and the hydrolysing activity was retained well even after trypsin was repeatedly used up to five times. Interestingly, the phosvitin phosphopeptides prepared with immobilised trypsin demonstrated a lower N/P ratio and a higher calcium-binding efficiency than those prepared with free trypsin. Furthermore, phosphopeptides significantly increased the rate of calcium absorption and serum calcium content in vivo. Based on these results, we conclude that trypsin immobilised onto chitosan has a greater phosvitin hydrolysing activity than free trypsin, and the prepared phosphopeptides can be used as a new calcium supplement to significantly increase calcium absorption in growing rats.

Status of Serum calcium, phosphorus and Vitamin D

2012 ◽  
Vol 2 (7) ◽  
pp. 329-330
Author(s):  
Saira Baloch ◽  
◽  
Bikha Ram Devrajani ◽  
Aneela Atta-ur-Rahman
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Calcium Phosphorus

P1237TISSUE-NONSPECIFIC ALKALINE PHOSPHATASE, A CULPRIT DURING ARTERIAL MEDIA CALCIFICATION BUT INDISPENSABLE DURING PHYSIOLOGICAL BONE FORMATION/-MINERALIZATION IN RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Britt Opdebeeck ◽  
José Millan Luis ◽  
Anthony Pinkerton ◽  
Anja Verhulst ◽  
Patrick D'Haese ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Vascular Calcification ◽  
Rat Model ◽  
Bone Mineralization ◽  
Calcium Content ◽  
Marker Genes ◽  
Peripheral Arteries ◽  
Calcium Phosphorus ◽  
Chondrogenic Marker

Abstract Background and Aims Vascular media calcification is frequently seen in elderly and patients with chronic kidney disease (CKD), diabetes and osteoporosis. Pyrophosphate is a well-known calcification inhibitor that binds to nascent hydroxyapatite crystals and prevents further incorporation of inorganic phosphate into these crystals. However, the enzyme tissue-nonspecific alkaline phosphatase (TNAP), which is highly expressed in calcified arteries, degrades extracellular pyrophosphate into phosphate ions, by which pyrophosphate loses its ability to block vascular calcification. Here, we aimed to evaluate whether a TNAP inhibitor is able to prevent the development of arterial calcification in a rat model of warfarin-induced vascular calcification. Method To induce vascular calcification, rats received a diet containing 0.30% warfarin and 0.15% vitamin K1 throughout the entire study and were subjected to the following daily treatments: (i) vehicle (n=10) or (ii) 10 mg/kg/day TNAP-inhibitor (n=10) administered via an intraperitoneal catheter from start of the study until sacrifice at week 7. Calcium, phosphorus and parathyroid hormone (PTH) levels were determined in serum samples as these are important determinants of vascular calcification. As TNAP is also expressed in the liver, serum alanine aminotransferase (ALT) and aspartate (AST) levels were analyzed. At sacrifice, vascular calcification was evaluated by measurement of the total calcium content in the arteries and quantification of the area % calcification on Von Kossa stained sections of the aorta. The mRNA expression of osteo/chondrogenic marker genes (runx2, TNAP, SOX9, collagen 1 and collagen 2) was analyzed in the aorta by qPCR to verify whether vascular smooth muscle cells underwent reprogramming towards bone-like cells. Bone histomorphometry was performed on the left tibia to measure static and dynamic bone parameters as TNAP also regulates physiological bone mineralization. Results No differences in serum calcium, phosphorus and PTH levels was observed between both study groups. Warfarin exposure resulted in distinct calcification in the aorta and peripheral arteries. Daily dosing with the TNAP inhibitor (10 mg/kg/day) for 7 weeks significantly reduced vascular calcification as indicated by a significant decrease in calcium content in the aorta (vehicle 3.84±0.64 mg calcium/g wet tissue vs TNAP inhibitor 0.70±0.23 mg calcium/g wet tissue) and peripheral arteries and a distinct reduction in area % calcification on Von Kossa stained aortic sections as compared to vehicle condition. The inhibitory effects of SBI-425 on vascular calcification were without altering serum liver markers ALT and AST levels. Furthermore, TNAP-inhibitor SBI-425 did not modulate the mRNA expression of osteo/chondrogenic marker genes runx2, TNAP, SOX9, collagen 1 and 2. Dosing with SBI-425 resulted in decreased bone formation rate and mineral apposition rate, and increased osteoid maturation time and this without significant changes in osteoclast- and eroded perimeter. Conclusion Dosing with TNAP inhibitor SBI-425 significantly reduced the calcification in the aorta and peripheral arteries of a rat model of warfarin-induced vascular calcification and this without affecting liver function. However, suppression of TNAP activity should be limited in order to maintain adequate physiological bone mineralization.

scholarly journals Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiqing Zhang ◽  
Sanjay Kumar ◽  
Muthuvel Jayachandran ◽  
Loren P. Herrera Hernandez ◽  
Stanley Wang ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Calcium Oxalate ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Kidney Stone ◽  
Fibroblast Growth Factor 23 ◽  
Pathogenic Mechanisms ◽  
Phosphorus Excretion ◽  
Stone Formers ◽  
Calcium Phosphorus

Abstract Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs). Methods Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. Results Urine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies. Conclusions Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

scholarly journals Dietary Calcium-Phosphorus Ratios for Growing Pigs in Relation to Serum Levels and Bone Development

1971 ◽  
Vol 12 (2) ◽  
pp. 202-219 ◽  
Author(s):  
N.C. Nielsen ◽  
S. Andersen ◽  
A. Madsen ◽  
H.P. Mortensen
Keyword(s):  
Bone Development ◽  
Serum Levels ◽  
Dietary Calcium ◽  
Growing Pigs ◽  
Calcium Phosphorus

Study of Calcium, Magnesium and Phosphorus Levels among Hypothyroid Patients in Trichy, Tamil Nadu

2021 ◽  
Vol 8 (30) ◽  
pp. 2797-2803
Author(s):  
Rasheed Khan M ◽  
Thivyah Prabha A.G ◽  
Siva Kumar K
Keyword(s):  
Serum Calcium ◽  
Tamil Nadu ◽  
Mineral Metabolism ◽  
Clinical Manifestations ◽  
Research Centre ◽  
Calcium Phosphorus ◽  
Calcium Magnesium ◽  
Hypothyroid Patients ◽  
Thyroid Dysfunctions

BACKGROUND Mineral metabolism is frequently disturbed in thyroid dysfunctions. Among thyroid dysfunctions, hypothyroidism is one of the most common form resulting from the deficiency of thyroid hormones. Studies done on serum calcium, phosphorus and magnesium in hypothyroid patients earlier have conflicting results. Hence the present study has been undertaken to study the levels of serum calcium, phosphorus, and magnesium among hypothyroid patients and analyse their correlation with thyroid stimulating hormone (TSH). METHODS The case control study was conducted in the Department of Biochemistry in Trichy SRM Medical College Hospital and Research Centre for a period of 6 months from 2017 January to July 2017. The study was undertaken involving 50 hypothyroid cases and 50 healthy volunteers as controls after proper ethical clearance and informed consent of all the study subjects. Serum calcium, phosphorus and magnesium were measured along with tri-iodothyronine (FT3), tetra-iodothyronine (FT4) and TSH among all study subjects. Statistical analysis of data was done using statistical package for social sciences (SPSS) software. RESULTS The mean value of serum total calcium and total magnesium was lower among hypothyroid cases and phosphorus value was increased as compared to controls. (P < 0.001) Statistically significant negative correlation was observed between serum calcium, magnesium and TSH among hypothyroid cases. Statistically significant positive correlation was observed between serum phosphorus and TSH among hypothyroid cases. CONCLUSIONS Among hypothyroid patients the values of serum calcium, magnesium and phosphorus is significantly altered. Thyroid disorders have an important role in bone and mineral metabolism. Thus, monitoring of these minerals among hypothyroid patients in regular follow up may effectively improve the clinical manifestations in them. Hence, monitoring of mineral status of the hypothyroid patients on follow-up will be of benefit to the patients. KEYWORDS Hypothyroidism, Calcium, Phosphorus, Magnesium, Minerals

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