Analytical performance of the Enhanced Liver Fibrosis (ELF) Test on the Atellica IM Analyzer.

Background: The Enhanced Liver Fibrosis (ELF) Test comprises 3 direct serum markers of fibrosis-hyaluronic acid (HA), amino-terminal pro-peptide of type III procollagen (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)-whose results are combined in an algorithm to generate the ELF score. Outside the U.S.

Analytical characterization of the SARS-CoV-2 EURM-017 reference material.

Background: Current serological methods for SARS-CoV-2 lack adequate standardization to a universal standard reference material. Standardization will allow comparison of results across various lab-developed and commercial assays and publications. SARS-CoV-2 EURM-017 is human sera reference material containing antibodies directed against SARS-CoV-2 proteins, S1/S2 (full-length spike [S]), S1 receptor-binding domain (S1 RBD), S1, S2, and nucleocapsid (N) protein.

Performance evaluation of four 25-hydroxyvitamin D assays to measure 25-hydroxyvitamin D2.

Objectives: The ability of current immunoassays to accurately measure equimolar amounts of 25(OH)D2 and 25(OH)D3 has been recently questioned. This study determined serum 25(OH)D2, 25(OH)D3 and total serum 25(OH)D concentrations in healthy vitamin D2-supplemented subjects by isotope dilution liquid chromatography mass spectrometry (ID-LC-MS/MS); and, evaluated the ability of the Siemens, DiaSorin, Roche, and Abbott Vitamin D Total assays to monitor total serum 25(OH)D concentrations compared to an ID-LC-MS/MS method traceable to the National Institute of Standards and Technology (NIST), and that has achieved certification from the Centers for Disease Control and Prevention (CDC) Vitamin D Standardization Certification Program (VDSCP).

Design And Methods: Twenty (20) healthy adults, with no history of prior vitamin D supplementation were administered oral vitamin D2 (2400IU/day for 6months).

FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice.

Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants.

Erratum to "Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay".

[This corrects the article DOI: 10.1155/2014/691679.].

Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay.

Vitamin D status in different populations relies on accurate measurement of total serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3 and 25(OH)D2].

FGF23 regulates renal sodium handling and blood pressure.

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. Here, we show that FGF23 directly regulates the membrane abundance of the Na(+):Cl(-) co-transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor/αKlotho complex, extracellular signal-regulated kinase 1/2 (ERK1/2), serum/glucocorticoid-regulated kinase 1 (SGK1), and with-no lysine kinase-4 (WNK4). Renal sodium (Na(+)) reabsorption and distal tubular membrane expression of NCC are reduced in mouse models of Fgf23 and αKlotho deficiency.

FGF23 promotes renal calcium reabsorption through the TRPV5 channel.

αKlotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid-5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, αKlotho also functions as the obligatory co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in Fgf23 knockout mice, similar to what is seen in αKlotho knockout mice.

Fibroblast growth factor 23 (FGF23) and alpha-klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization.

Elevated serum levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) are found in patients with phosphate wasting diseases and chronic kidney disease-mineral and bone disorder (CKD-MBD). These diseases are associated with rickets and renal osteodystrophy, respectively. FGF23 is secreted from osteoblastic cells and signals through FGFRs, membrane coreceptor alpha-Klotho (Klotho), and, possibly, a circulating form of Klotho.

Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo.

Fibroblastic growth factor 23 (FGF23) is a bone-derived hormone that has a pivotal role in the pathogenesis of mineral disorders in chronic kidney disease. To study the effect of parathyroid hormone (PTH) on FGF23, rats were parathyroidectomized for a week and then implanted with constant-delivery infusion pumps to provide vehicle, a physiological, or a threefold supraphysiological dose of parathyroid hormone. Parathyroidectomy resulted in a significant decrease in blood ionized calcium, FGF23, and calcitriol along with an increase in phosphorus concentrations.

Chondro/osteoblastic and cardiovascular gene modulation in human artery smooth muscle cells that calcify in the presence of phosphate and calcitriol or paricalcitol.

Vitamin D sterol administration, a traditional treatment for secondary hyperparathyroidism, may increase serum calcium and phosphorus, and has been associated with increased vascular calcification (VC). In vitro studies suggest that in the presence of uremic concentrations of phosphorus, vitamin D sterols regulate gene expression associated with trans-differentiation of smooth muscle cells (SMCs) to a chondro/osteoblastic cell type. This study examined effects of vitamin D sterols on gene expression profiles associated with phosphate-enhanced human coronary artery SMC (CASMC) calcification.

FGF23 fails to inhibit uremic parathyroid glands.

Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D(3). FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats.

The calcimimetic AMG 641 abrogates parathyroid hyperplasia, bone and vascular calcification abnormalities in uremic rats.

Calcimimetics and vitamin D sterols reduce serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism receiving dialysis, a disease state associated with parathyroid hyperplasia, vascular calcification, bone disease, and increased mortality. The aim of this study was to determine the effects of the research calcimimetic AMG 641 (Amgen, Inc., Thousand Oaks, CA) or calcitriol (Sigma Aldrich Corporation, St.

Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis.

Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone.

Unlabelled: Skeletal anabolism with PTH is achieved through daily injections that result in brief exposure to the peptide. We hypothesized that similar anabolic effects could be achieved with less frequent but more sustained exposures to PTH. A PTH-Fc fusion protein with a longer half-life than PTH(1-34) increased cortical and cancellous BMD and bone strength with once- or twice-weekly injections.

Calcification inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols.

Administration of active vitamin D sterols to treat secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis has been associated with elevated serum calcium and phosphorus levels, which may lead to increased risk of vascular calcification. However, calcimimetics, by binding to the parathyroid gland calcium-sensing receptors, reduce serum parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. Using cultured bovine aorta vascular smooth muscle cells (BASMCs), an in vitro model of vascular calcification, we compared calcification levels and gene expression profiles after exposure to the phosphate source ss-glycerolphosphate (BGP), the active vitamin D sterols calcitriol and paricalcitol, the calcimimetic R-568, or BGP with the active vitamin D sterols or R-568.

The receptor activator of nuclear factor-kappaB ligand inhibitor osteoprotegerin is a bone-protective agent in a rat model of chronic renal insufficiency and hyperparathyroidism.

Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-kappaB ligand (RANKL), the primary mediator of osteoclast differentiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was induced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.

In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells.

This study examined whether the calcium-sensing receptor (CaR) is expressed in normal adult human osteoblastic and osteoclastic cells in culture, and whether the calcimimetic, cinacalcet HCl (AMG 073), potentiates the effects of calcium (via CaR, or some other receptor/mechanism). When mouse or human osteoblastic cells were treated with higher concentrations of calcium (6.6 or 8.

Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption.

OPG is a new member of the tumor necrosis factor (TNF) receptor family which plays a key role in the physiological regulation of osteoclastic bone resorption. The protein, which is produced by osteoblasts and marrow stromal cells, lacks a transmembrane domain and acts as a secreted decoy receptor which has no direct signaling capacity. OPG acts by binding to its natural ligand OPGL, which is also known as RANKL (receptor activator of NF-kappaB ligand).

Characterization of osteoclast precursors in human blood.

Osteoclast precursors (OCPs) circulate in the mononuclear fraction of peripheral blood (PB), but their abundance and surface characteristics are unknown. Previous studies suggest that the receptor activator for NF-kappaB (RANK) on cytokine-treated OCPs in mouse bone marrow interacts with osteoprotegerin ligand (OPGL/TRANCE/RANKL/ODF) to initiate osteoclast differentiation. Hence, we used a fluorescent form of human OPGL (Hu-OPGL-F) to identify possible RANK-expressing OCPs in untreated peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analysis.

Cytokine RNA levels in transiliac bone biopsies from healthy early postmenopausal women.

The cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6 induce osteoclast formation and may contribute to the development of postmenopausal osteoporosis. Cross-sectional studies have suggested that both IL-1 and IL-1ra secretion increase on estrogen withdrawal, and that postmenopausal osteoporosis is associated with an inadequate increase in monocyte IL-1ra secretion with age. We measured cytokine mRNA (IL-1beta, IL-1ra, IL-6, and TNF-alpha) directly in bone biopsies from early postmenopausal women to determine if a lower compensatory increase in IL-1ra mRNA could be demonstrated in women with rapid bone loss after the menopause.