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• FGF23 clearance in hemodialysis patients

In Chronic Kidney Disease (CKD), fibroblast growth factor 23 (FGF23) acts as a cardiovascular toxin by contributing to hypertension, vascular calcification, and left ventricular hypertrophy, leading to increased cardiovascular risk and mortality (1). 

FGF23 clearance in hemodialysis patients

In a recent study researchers explored whether the use of different dialysis membranes result in a reduction of FGF23 and other inflammatory cytokine levels (IL-6, IL-18, dp-ucMGP, and hsCRP) in hemodialysis patients.

A Randomised Prospective Crossover Study on the Effects of Medium Cut-Off Membranes on FGF-23 and Inflammatory Mediators in Patients Receiving Regular Haemodialysis. Al-Chalabi S, et al., 2025. Blood Purif.

Abstract

Introduction: In contrast to high-flux dialysis (HFD) membranes, medium cut-off membranes (MCO) can potentially remove a wide range of middle molecules. Our study aimed to compare the clearance rate (CR) of fibroblast growth factor 23 (FGF-23) and other selected inflammatory cytokines between medium MCO and HFD membranes and investigate the intrasubject stability of these biomarkers.

Methods: This prospective randomised case-crossover study recruited 20 adult patients who were randomised into two groups: group A: to start with 1 week of thrice-weekly dialysis using HFD membrane followed by a 3-week washout period and then 1 week of dialysis with an MCO membrane. Group B followed the reverse sequence. Blood samples were taken before and after each dialysis session for the analysis of the assessed biomarkers (FGF-23, interleukin-6 [IL-6], interleukin-18 [IL-18], high-sensitivity C-reactive protein [hsCRP], and dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP]). Wilcoxon signed rank and paired t tests were used for comparison between the membranes. One-way repeated measures ANOVA or Friedman tests were used for the intrasubject stability of the biomarkers.

Results: The use of both MCO and HFD membranes resulted in a significant reduction of FGF-23 levels and other selected inflammatory cytokines. However, there was no significant difference in the CR: FGF-23 (0.31 vs. 0.23], p = 0.242), IL-6 (0.19 vs. 0.12, p = 0.215), IL-18 (-0.05 vs. -0.03, p = 0.704), dp-ucMGP (0.33 vs. 0.33, p = 0.903), and hsCRP (-0.05 vs. -0.08, p = 0.107). There was no significant intrasubject variability for all assessed biomarkers except in pre-dialysis high hsCRP levels when using HFD membrane.

Conclusion: The use of both MCO and HFD membranes resulted in a significant reduction of FGF-23 levels and other selected inflammatory cytokines. However, the MCO membrane did not demonstrate a significant advantage over the HFD in the short term. There was no significant intrasubject variability for all assessed biomarkers apart from hsCRP.

 

BIOMEDICA´s FGF23 and IL-6 ELISA Assay Kits were successfully utilized in the study:

 

FGF23 (C-terminal) multi-matrix ELISA Kit | BI-20702

• Instructions for use
• Validation data file
• Citations

 

IL-6 (Interleukin-6) ELISA Kit | BI-IL6

• Instructions for use
• Validation data file
• Citations

 

 

Related Products:

-Intact FGF23 ELISA Kit | BI-20700

–NT-proBNP ELISA | SK-1204

 

Literature

1. FGF23 and Phosphate-Cardiovascular Toxins in CKD. Toxins (Basel). Vogt I, Haffner D, Leifheit-Nestler M. 2019 Nov 6;11(11):647. doi: 10.3390/toxins11110647. PMID: 31698866; PMCID: PMC6891626.
2. A Randomised Prospective Crossover Study on the Effects of Medium Cut-Off Membranes on FGF-23 and Inflammatory Mediators in Patients Receiving Regular Haemodialysis. Al-Chalabi S, Sinha S, Kalra PA, Evans D, Green D, Schurgers L, Poulikakos D. Blood Purif. 2025 Apr 21:1-13. doi: 10.1159/000545745. Epub ahead of print. PMID: 40258362; PMCID: PMC12105827.

September is Blood Cancer Awareness Month raising awareness about the various types of blood cancers, including leukemia, lymphoma, multiple myeloma, and other hematologic malignancies. The goal of this initiative is to educate the public about the symptoms and the importance of early detection and treatment.

Multiple myeloma (MM) is the second most common blood cancer and the most prevalent type of cancer affecting the bones.

MM-related bone disease (MMBD) has severe implications for patients, leading to significant bone loss, intense bone pain, and pathological fractures that greatly impair quality of life and influence survival outcomes. Multiple myeloma bone disease (MMBD) results from disrupted bone remodeling, marked by increased activity of osteoclasts, breaking down bone and decreased activity of osteoblasts (1, 2).

September is Blood Cancer Awareness Month

Daratumumab is a monoclonal antibody used primarily in the treatment of multiple myeloma. It works by targeting a specific protein called CD38, which is highly expressed on the surface of myeloma cells. By binding to CD38, daratumumab helps the immune system recognize and attack the cancer cells, leading to their destruction. Daratumumab is often used in combination with other therapies and has shown significant effectiveness in improving response rates and survival outcomes for patients with multiple myeloma. It is administered via intravenous infusion and may be associated with side effects such as infusion reactions, fatigue, nausea, and increased risk of infections (3).

In the “REBUILD” Study researchers investigated how Daratumumab impacts bone metabolism in patients with relapsed or refractory multiple myeloma. The Phase 2 “REBUILD” trial aims to assess whether treatment with daratumumab can improve bone turnover markers and potentially help repair bone damage associated with the disease. The findings suggest that Daratumumab not only targets myeloma cells but may also positively influence bone health in affected patients (3)

Daratumumab Improves Bone Turnover in Relapsed/Refractory Multiple Myeloma; Phase 2 Study “REBUILD”. Terpos E et al., .Cancers (Basel). 2022.  

Abstract

Biomarkers of bone turnover in serum are suggestive of bone dynamics during treatment in multiple myeloma (MM). We evaluated the role of daratumumab on bone remodeling among patients with relapsed/refractory MM in the prospective, open-label, phase 2 study REBUILD. Daratumumab was administered according to the approved indication. A total of 33 out of 57 enrolled patients completed 4 months of treatment. The median percent change from baseline to 4 months in C-terminal cross-linking telopeptide of type 1 collagen (CTX) (primary endpoint) was 3.9%, with 13 (39.4%) and 11 (33.3%) patients showing at least 20% and 30% reduction in CTX levels, respectively. The median percent decrease from baseline to 4 months in tartrate resistant acid phosphatase 5b (TRACP-5b) levels (co-primary endpoint) was 2.6%, with 10 (30.3%) and 6 (18.2%) patients showing at least 20% and 30% reduction in TRACP-5b levels, respectively. However, the changes in these markers of bone catabolism were not statistically significant. Furthermore, the levels of osteocalcin, bone-specific alkaline phosphatase and procollagen type-I N-pro-peptide (bone formation markers) increased from baseline to 4 months (secondary endpoints) by 18.4%, 92.6% and 10.2%, respectively. Furthermore, the median levels of dickkopf-1 and C-C motif ligand-3 showed a significant decrease at 4 months by 17.5% and 16.0%, respectively. In conclusion, daratumumab improved bone turnover by inducing bone formation and reducing osteoblast inhibition.

 Evaluation of Bone Remodeling

The following serum markers of bone metabolism were measured with

Biomedica ELISA assays:

• Soluble RANKL (BI-20462)
• Osteoprotegerin – OPG (BI-20403)
• Sclerostin (BI-20492)
• Dickkopf-1 – DKK-1 (BI-20413)

 

Discover our Biomarker ELISA Kit Collection

 

Literature

1. Multiple myeloma. Nat Rev Dis Primers. Malard F, Neri P, Bahlis NJ, Terpos E, Moukalled N, Hungria VTM, Manier S, Mohty M.2024 Jun 27;10(1):45. doi: 10.1038/s41572-024-00529-7. PMID: 38937492.
2. Multiple Myeloma and Bone: The Fatal Interaction. Marino S, Roodman GD. Cold Spring Harb Perspect Med. 2018 Aug 1;8(8):a031286. doi: 10.1101/cshperspect.a031286. PMID: 29229668; PMCID: PMC6071546.
3. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, Lindsay J, Baker RI, Suzuki K, Kosugi H, Levin MD, Beksac M, Stockerl-Goldstein K, Oriol A, Mikala G, Garate G, Theunissen K, Spicka I, Mylin AK, Bringhen S, Uttervall K, Pula B, Medvedova E, Cowan AJ, Moreau P, Mateos MV, Goldschmidt H, Ahmadi T, Sha L, Cortoos A, Katz EG, Rousseau E, Li L, Dennis RM, Carson R, Rajkumar SV; AQUILA Investigators. N Engl J Med. 2025 May 8;392(18):1777-1788. doi: 10.1056/NEJMoa2409029. Epub 2024 Dec 9. PMID: 39652675.

With over 30 years of experience in developing and manufacturing high quality ELISA kits we provide scientists and healthcare professionals with tests that enable discoveries and support the translation of research into diagnostics.

All Kits are developed & manufactured by Biomedica Immunoassays – Austrian Quality!

 

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Trusted and widely cited ELISA assays for biomarkers in bone metabolism, cardiovascular and renal diseases, cancer and oxidative stress.

Biomedica´s ELISA Kits – Features & Benefits

• EASY – ready to use calibrators & controls included (color-coded reagents)
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• WIDELY CITED in over 2500 publications

 

Discover our Biomarker ELISA Kit Collection

BONE 

Sclerostin (SOST), Osteoprotegerin (OPG), Free soluble RANKL (sRANKL), Periostin (POSTN)

Fibroblast Growth Factor (C-terminal and intact) FGF23 intact, FGF23 (C-terminal)

related citations:

• Sclerostin ELISA (BI-20492) : The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomized controlled crossover trial. 
• FGF23 ELISAs (BI-20702, BI-20700): C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. 

 

CARDIOASCULAR

Natriuretic Peptides: NT-proANP (for human and preclinical use), NT-proBNP, NT-proCNP,                  

Endothelins: Big Endothelin-1 (Big ET-1)

Rat NT-proBNP

• related citation: rat NT-proBNP ELISA (BI-1204R): Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition.

 

KIDNEY   

Endostatin, Vanin-1

• related citation Vanin-1 ELISA (BI-VAN1U): The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study. 

 

CANCER

Semaphorin 4D, Neuropilin-1, Leucine-rich alpha-2-glycoprotein (LRG1), Periostin 

• related citation LRG-1 ELISA (BI-LRG): High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. 

 

OXIDATIVE STRESS   

Autoantibodies to oxidized low density lipoprotein (anti-oxLDL AB – oLAB)

OxyStat – detection of biological peroxides

• related citation oxLDL – oLAB ELISA (BI-20032): Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.

 

TRANSPLANTATION    

anti-C4D antibody

• related citation anti-C4d Antibody (BI-RC4D): Complement Activation Is Associated With Crescents in IgA Nephropathy. 

 

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Related Literature

An overview of ELISA: a review and update on best laboratory practices for quantifying peptides and proteins in biological fluids. Aydin S, Emre E, Ugur K, Aydin MA, Sahin İ, Cinar V, Akbulut T. J Int Med Res. 2025 Feb;53(2):3000605251315913. doi: 10.1177/03000605251315913. PMID: 39922798; PMCID: PMC11808753.

Abstract

The enzyme-linked immunosorbent assay (ELISA) detects antigen-antibody interactions by using enzyme-labelled conjugates and enzyme substrates that generate colour changes. This review aims to provide an overview of ELISA, its various types, and its applications in detecting metabolites in biological fluids. The article discusses the history of the assay, its underlying principles and procedures, common ELISA protocols, and the most accurate and reliable techniques for measuring peptide molecules in biological fluids. Additionally, we emphasize best laboratory practices to achieve consistent, high-quality results and outline the essential materials for setting up an ELISA laboratory, drawing from our over 30 years of experience in the field.

Comparison between a Luminex-based multiplex kit with a sequence-specific oligonucleotide probe and next-generation sequencing for the detection of POLE oncogenic mutations in endometrial cancer. Kato MK, Kawai T, Okada H, Kondo T, Shiraishi T, Yamaguchi M, Higuchi D, Komatsu M, Hamamoto R, Matumoto K, Terao Y, Kato T, Kohno T, Ishikawa M, Shiraishi K, Yoshida H. Virchows Arch. 2025 Aug 4. doi: 10.1007/s00428-025-04204-4. Epub ahead of print. PMID: 40760194.

We operate in more than 60 countries, providing wide access and customer support through collaborations with carefully chosen local distributors on nearly every continent. No matter where you are, we’re committed to helping you achieve your objectives. With over 30 years of expertise, we focus on designing and manufacturing premium ELISA assay kits for biomarker detection in clinical research.

About us

We develop and produce high-quality ELISA assay kits for clinical and pre-clinical applications related to bone and cardio-renal diseases. Our assays are cited in more than 2500 publications and some of our kits are the most referenced on the market Sclerostin, free soluble RANKL, Periostin, NT-proCNP and many others.

Our ELISA Kits Go Global

All Biomedica ELISA assays undergo a full validation following international quality guidelines (the validation package for every kit can be found on the respective product pages on our website. Validation criteria include recovery, dilution linearity, parallelism, matrix effect testing and many others.

Our ELISA kits include ready-to-use serum-based calibrators and controls enabling researchers to collect biologically reliable data.

 

Features & Benefits of BIOMEDICA ELISA Assay Kits

• Trusted – cited in over 2500 publications
• Highly specific – characterized epitope-mapped antibodies

• Full validation package – following international quality guidelines
• Convenient – ready to use, color coded reagents – controls included 

 

Biomarker ELISA Assays for Bone-Mineral Metabolism & Cardio-Renal Diseases

 –Intact FGF23 ELISA Kit | BI-20700

–FGF23 (C-terminal) multi-matrix ELISA Kit | BI-20702

–Sclerostin ELISA | BI-20492

–FREE soluble RANKL HS ELISA | BI-20462

–Periostin ELISA | BI-20433

–OPG ELISA Kit (Human Osteoprotegerin) | BI-20403

–NT-proBNP ELISA | SK-1204

–Rat NT-proBNP ELISA | BI-1204R

–NT-proANP ELISA | BI-20892

 

Selected citations

Fibroblast Growth Factor 23, Endogenous Erythropoietin, Erythropoiesis-Stimulating Agents, and Erythropoietin Resistance in Hemodialysis Patients.  Hamano N et al.,2025;  Am J Nephrol.

Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF et al., 2023; Diabetes Metab Res Rev.

The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomised controlled crossover trial. Coombs CV et al., 2025; J Bone Miner Res.  

Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S et a., 2024; Cardiovasc Diabetol.

 

 

Our proANP ELISA was featured in a recent study investigating the effect of Atrial natriuretic peptide (ANP) in the regulation of endothelial autophagy in human umbilical vein endothelial cells (HUVECs) (1). Autophagy is a lysosome-mediated degradation process vital for cell survival, differentiation, development, and maintaining homeostasis. Its primary function is to act as an adaptive mechanism, helping organisms defend against various conditions such as infections, cancer, neurodegenerative disorders, aging, and cardiovascular diseases (2).

ANP activates autophagy in endothelial cells

ANP is a hormone mainly produced by the atria of the heart, especially in response to increased stretch caused by higher blood volume or pressure. ANP is vital for managing blood volume and pressure by encouraging the excretion of sodium (natriuresis), water (diuresis), and causing blood vessels to dilate (vasodilation) (3). Additionally, it suppresses the renin-angiotensin-aldosterone system (RAAS), which further helps to lower blood pressure. Interestingly, ANP has recently been identified as an extracellular regulator of cardiac autophagy (4).

Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells. Forte M et al., Biochim Biophys Acta Mol Cell Res. 2025 

Key findings:

-ANP quickly enhances autophagy in endothelial cells

-Endothelial cells rapidly secrete ANP under stress conditions promoting stress-induced autophagy

-The protective effects of ANP, such as in response to high-salt conditions, are diminished when autophagy is inhibited

Conclusion: the results suggest that ANP functions as an endogenous activator of autophagy in endothelial cells, with autophagy mediating its protective effects on the endothelium.

NT proANP ELISA | BI-20892

• CONVENIENT – Small sample volume – 10 µl / well
• HIGH QUALITY – Full validation package
• TRUSTED – cited in over 170 publications
• EASY – color coded and ready to use reagents
• FLEXIBLE- assay is suitable for human and non-human samples (rodents and others)

 

 

Related ELISA kits:

NT-proCNP ELISA | BI-20812

NT-proBNP ELISA | SK-1204

Rat NT-proBNP ELISA | BI-1204R

 

Literature:

1. Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells. Forte M, Marchitti S, di Nonno F, Pietrangelo D, Stanzione R, Cotugno M, D’Ambrosio L, D’Amico A, Cammisotto V, Sarto G, Rocco E, Simeone B, Schiavon S, Vecchio D, Carnevale R, Raffa S, Frati G, Volpe M, Sciarretta S, Rubattu S. Biochim Biophys Acta Mol Cell Res. 2025 Jan;1872(1):119860. doi: 10.1016/j.bbamcr. 2024.119860. Epub 2024 Oct 9. PMID: 39383950.
2. Autophagy in the pathogenesis of disease. Levine B, Kroemer G. Cell. 2008 Jan 11;132(1):27-42. doi: 10.1016/j.cell.2007.12.018. PMID: 18191218; PMCID: PMC2696814.
3. Cardiac natriuretic peptides. Goetze JP, Bruneau BG, Ramos HR, Ogawa T, de Bold MK, de Bold AJ. Nat Rev Cardiol. 2020 Nov;17(11):698-717. doi: 10.1038/s41569-020-0381-0. Epub 2020 May 22. PMID: 32444692.
4. NPPA/atrial natriuretic peptide is an extracellular modulator of autophagy in the heart. Forte M, Marchitti S, Di Nonno F, Stanzione R, Schirone L, Cotugno M, Bianchi F, Schiavon S, Raffa S, Ranieri D, Fioriniello S, Della Ragione F, Torrisi MR, Carnevale R, Valenti V, Versaci F, Frati G, Vecchione C, Volpe M, Rubattu S, Sciarretta S.Autophagy. 2023 Apr;19(4):1087-1099. doi: 10.1080/15548627.2022.2115675. Epub 2022 Sep 6. PMID: 35998113; PMCID: PMC10012953.

 

Arterial stiffness (AS) is characterized by stiffening of the vascular wall, which diminishes its ability to expand and contract in response to blood flow. It is a natural aspect of aging, driven by structural and cellular alterations in the vessel walls, and tends to accelerate in the presence of cardiovascular risk factors like diabetes, hypertension, and others (1). The development of AS involves dysregulation of elastin fibers and collagen, oxidative stress, disrupted mineral metabolism, and low-grade inflammation. Multiple factors contribute to its progression, including oxidative stress, inflammation, vascular calcification, and the combined effects of traditional cardiovascular risk factors such as diabetes mellitus and hypertension (2). Arterial stiffness can lead to increased myocardial preload and decreased perfusion pressure in the coronary arteries. Importantly, AS is a predictor of future cardiovascular disease (CVD), as heightened arterial stiffness can cause higher systolic blood pressure, increased cardiac workload, and a greater likelihood of events like heart attack and stroke (3).

Sclerostin is associated with risk for arterial stiffness

Sclerostin is primarily known for its role in controlling bone formation, but it is also expressed in the heart, aorta, and arteries (4). A recent study in community dwelling women revealed that lower serum sclerostin levels were associated with elevated risks for increased AS (5).

Sclerostin levels were measured with the

Biomedica SCLEROSTIN ELISA Assay | BI-20492

• most referenced in over 300 publications
• full validation package
• for serum and plasma – sample volume: 20µl / well

 

 

Example of a typical ELISA assay with color coded, ready to use reagents

Literature:

1. Arterial Stiffness in Aging: Does It Have a Place in Clinical Practice?: Recent Advances in Hypertension. Mitchell GF. Hypertension. 2021 Mar 3;77(3):768-780. doi: 10.1161/HYPERTENSIONAHA.120.14515. Epub 2021 Feb 1. PMID: 33517682..
2. Hypertension, Arterial Stiffness, and Diabetes: a Prospective Cohort Study. Tian X, Zuo Y, Chen S, Zhang Y, Zhang X, Xu Q, Wu S, Wang A. Hypertension. 2022 Jul;79(7):1487-1496. doi: 10.1161/HYPERTENSIONAHA.122.19256. Epub 2022 May 16. PMID: 35574838; PMCID: PMC9172905.
3. Role of arterial stiffness in cardiovascular disease. Cecelja M, Chowienczyk P. JRSM Cardiovasc Dis. 2012 Jul 31;1(4):cvd.2012.012016. doi: 10.1258/cvd.2012.012016. PMID: 24175067; PMCID: PMC3738327.
4. Role of Sclerostin in Cardiovascular Disease. Golledge J, Thanigaimani S. Arterioscler Thromb Vasc Biol. 2022 Jul;42(7):e187-e202. doi: 10.1161/ATVBAHA.122.317635. Epub 2022 May 12. PMID: 35546488.
5. Association of Lower Serum Sclerostin Levels With Elevated Risk for Increased Arterial Stiffness: The JPOS Cohort Study. Tamaki J, Tachiki T, Jaalkhorol M, Dongmei N, Komastu M, Tsuda K, Kudo A, Kamiya K, Kouda K, Kajita E, Kagamimori S, Iki M. J Clin Endocrinol Metab. 2025 Jul 15;110(8):2225-2235. doi: 10.1210/clinem/dgae795. PMID: 39530177.

Antibody-mediated rejection (ABMR) is the major cause of renal graft dysfunction and loss (1). Currently, renal biopsy remains the gold standard for diagnosing rejection (2). C4d staining in kidney biopsies is widely used to identify the presence of complement activation in the small blood vessels and its deposition is a strong indicator of ABMR (3). In a new study, researchers have used our C4d antibody to identify ABMR and to investigate the diagnostic capacity of non-invasive biomarkers for detecting ABMR in kidney transplant recipients (2).

Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Vázquez-Toledo MA et al., Int J Mol Sci. 2025.

Abstract

Antibody-mediated rejection (ABMR) remains a major cause of renal graft dysfunction and loss. The histological hallmark of antibody-mediated rejection is progressive tissue damage, in which extracellular matrix turnover plays an important role. This turnover is mainly regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Recent studies suggest that MMP/TIMP imbalance may favor the progression of renal damage, inflammation, and fibrosis, but the utility of these molecules as a biomarker of antibody-mediated turnover has not been fully explored. We measured plasma MMP and TIMP levels by ELISA in 15 patients with antibody-mediated renal transplant rejection and 12 patients without rejection. There was a significant increase in MMP-1, MMP-2, and MMP-3 concentrations in the plasma of patients with rejection, directly correlating with the severity of different renal lesions. In contrast, TIMP-3 levels were elevated in patients without rejection, showing a negative correlation with the severity of histopathological lesions. The concentrations of these molecules demonstrated good diagnostic capacity for patients with rejection. Our results show that MMP-1, MMP-2, MMP-3, and TIMP-3 could be potential biomarkers of rejection.

> C4d antibodies by BIOMEDICA – for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry. 

 

 

Anti-C4dAntibody | BI-RC4D

• widely cited in over 100 publications 

• for immunohistochemistry on paraffin embedded tissue and frozen sections 

• use in kidney, heart, liver and other transplants 

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC 

• protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry 

• for kidney, heart, liver and other transplants 

 

Literature:

1. Antibody-mediated rejection of renal allografts: diagnostic pitfalls and challenges. Novotný M, Kment M, Viklický O. Physiol Res. 2021 Dec 30;70(Suppl4):S551-S565. doi: 10.33549/physiolres.934801. PMID: 35199543; PMCID: PMC9054191.
2. Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Vázquez-Toledo MA, Sánchez-Muñoz F, Zepeda-Quiroz I, Guzmán-Martín CA, Osorio-Alonso H, Daniel JV, Soto-Abraham MV, Moguel-González B, Chacón-Salinas R, Flores-Gama C, Springall R.Int J Mol Sci. 2025 Jun 23;26(13):6011. doi: 10.3390/ijms26136011. PMID: 40649789; PMCID: PMC12250063.
3. The importance of C4d in biopsies of kidney transplant recipients. Corrêa RR, Machado JR, da Silva MV, Helmo FR, Guimarães CS, Rocha LP, Faleiros AC, dos Reis MA. Clin Dev Immunol. 2013;2013:678180. doi: 10.1155/2013/678180. Epub 2013 Jul 9. PMID: 23935649; PMCID: PMC3722852.

Osteosarcoma (OS) is the most prevalent form of bone cancer affecting children and adolescents, often during periods of rapid bone growth (1). The primary pathophysiological process involves various potential genetic factors associated with bone formation that contribute to malignant progression and the spread of the disease (2). In recent years, plasma NT-proCNP levels and height velocity in children, along with CNP itself, have been recognized as emerging new markers of growth during childhood (3). CNP is essential for linear growth, being produced in the growth plate and acting via a paracrine signaling mechanism (4). The C-type natriuretic peptide (CNP) and its receptor, NPR-B, are essential in the process of endochondral bone development and growth. CNP functions as a local regulator, promoting bone growth via its receptor, NPR-B, a guanylyl cyclase. The fragment NT-proCNP, derived from CNP, serves as a valuable biomarker for tracking linear growth in children, especially during puberty (5).

NT-proCNP a potential biomarker for osteosarcoma

In a recent study researchers examined serum N-terminal pro C-type natriuretic peptide (NT-proCNP) at diagnosis and remission in children with osteosarcoma  (6). The Biomedica NT-proCNP ELISA (BI-20812) was employed in the study.

Key findings:

NT-proCNP concentrations

– were significantly lower in OS patients compared to controls

– were elevated at diagnosis compared to remission phases

– NT-proCNP could serve as a potential biomarker in monitoring disease progression and remission status in OS patients

NT-proCNP ELISA kit  (cat.no. BI-20812)

-Trusted – widely cited in over 50 publications

-Validated – following quality guidelines (download validation data here)

 

Literature

1. Osteosarcoma. Eaton BR, Schwarz R, Vatner R, Yeh B, Claude L, Indelicato DJ, Laack N. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28352. doi: 10.1002/pbc.28352. Epub 2020 Aug 11. PMID: 32779875.
2. Osteosarcoma. Beird HC, Bielack SS, Flanagan AM, Gill J, Heymann D, Janeway KA, Livingston JA, Roberts RD, Strauss SJ, Gorlick R. Nat Rev Dis Primers. 2022 Dec 8;8(1):77. doi: 10.1038/s41572-022-00409-y. Erratum in: Nat Rev Dis Primers. 2022 Dec 30;8(1):82. doi: 10.1038/s41572-022-00416-z. PMID: 36481668.
3. Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth – PubMed (nih.gov) Espiner E, Prickett T, Olney R. Horm Res Paediatr. 2018;90(6):345-357. doi: 10.1159/000496544. Epub 2019 Mar 7. PMID: 30844819.
4. Dynamic response of C-type natriuretic peptide and its aminoterminal propeptide (NTproCNP) to growth hormone treatment in children with short stature. Olney RC et al., Clin Endocrinol, 2016; 85(4):561-568.
5. C-type natriuretic peptide and its contribution to bone growth. Kulik-Rechberger B, Trojanowska-Szostek M Ann Agric Environ Med. 2022 Jun 24;29(2):252-257. doi: 10.26444/aaem/140076. Epub 2021 Jul 26. PMID: 35767759.

6. Investigation of serum C-type natriuretic peptide concentration at diagnosis and remission in pediatric osteosarcomas. Özdemir Sİ, Akcan G, Tufan AÇ, Erdem AY, Çakmakcı S, Özyörük D, Sarı N, Tufan NLŞ, İlhan İE. Eur J Pediatr. 2025 Jan 6;184(1):116. doi: 10.1007/s00431-024-05949-x. PMID: 39757264.

We´re thrilled to share that our rat NT-proBNP ELISA kit (BI-1204R) was recently reviewed on Biocompare. The researchers stated “we are highly satisfied with the results, as we clearly observed clinically relevant rat NT-proBNP levels and the anticipated changes from baseline to completion.”

Read the review on Biocompare and click here:

-The good: Requires minimal sample volume, supports room temperature reactions, includes sufficient reagents for three runs in duplicate, and comes with a built-in control.

-The Bottom Line : A straightforward and easy-to-use kit with color-coded reagents, requiring only a small sample volume and room temperature incubations. Provides sufficient reagents for at least three runs in duplicate, and delivers clinically relevant data.

The investigators evaluated the impact of platelet transfusion on TACO development in a validated TACO rat model with heart failure.

Background:

• Transfusion-associated circulatory overload (TACO) accounts for 35% of transfusion-related fatalities.
• TACO after platelet transfusion has an increased mortality

Key findings:

• Platelet transfusion significantly increases Left Ventricular End-Diastolic Pressure (LVEDP)
• Platelet transfusion induces oxygenation impairment
• NT-proBNP is a biomarker supportive of TACO development
• Clinically, the results highlight the importance of cautious use of both plasma and platelet transfusions, particularly in high-risk patients

Figure: Rat NT-proBNP level changes in a preclinical model with myocardial infarction

Rat NT-proBNP – clinically relevant levels in TACO rat model

Platelet transfusion induces transfusion-associated circulatory overload in rats with myocardial infarction. Phelp PG et al.,Transfusion. 2025 Jul;65(7):1251-1263. PMID: 40384327.

Abstract

Background: Transfusion-associated circulatory overload (TACO) accounts for 35% of transfusion-related fatalities. Previous pre-clinical studies explored plasma and red blood cell transfusion in TACO, but the effect of platelets remains unexplored. Platelet transfusions have the highest rate of adverse reactions and are associated with increased mortality in TACO patients. We aimed to determine whether platelet transfusion induces circulatory overload compared to crystalloids and whether it causes a more severe phenotype than plasma in a TACO rat model of myocardial infarction (MI).

Methods: A validated TACO model in anemic Wistar rats with MI was used. Animals received platelets (n = 11), plasma (n = 10), or Ringer’s lactate (n = 11). Pulmonary capillary pressure was assessed via left-ventricular end-diastolic pressure (LVEDP). The primary outcome was the change in LVEDP (ΔLVEDP) following transfusion. Secondary outcomes included pulmonary wet/dry weight ratio, oxygen tension or partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio, and circulating biomarkers.

Results: LVEDP following platelet transfusion (10.4 ± 4.6 mmHg) was significantly greater than Ringer’s lactate (0.9 ± 1.4 mmHg; p < .001), but similar to plasma (13.0 ± 7.7 mmHg; p > .5). Pulmonary wet/dry weight ratios were comparable across groups (p > .5). At termination, PaO₂/FiO₂ ratio was significantly lower after platelet transfusion (372 ± 48) compared to Ringer’s Lactate (447 ± 79; p < .05). N-terminal prohormone of brain natriuretic peptide (NT-proBNP) did not differ between groups at termination (p > .1). However, NT-proBNP significantly increased from baseline (50 ± 24 pg/mL) to termination (177 ± 86 pg/mL) across all groups (p < .001).

Discussion: Platelet transfusion induces circulatory overload in a TACO rat model with heart failure when compared to crystalloids, showing a trend toward reduced oxygenation compared to plasma transfusion. Further investigation is needed to determine the pathophysiological mechanisms.

 

Rat NT-proBNP ELISA (cat. no. BI-1204R)

• Size: 12×8-well detachable strips
• Sensitivity: LOD: 21 pg/ml; LLOQ: 50 pg/ml
• Dynamic Range: 0 – 3200 pg/ml (0 / 100 / 200 / 400 / 800 / 1600 / 3200)
• Sample Type: rat serum, plasma
• Sample Size: 10 µL/well
• Assay time: 3.5 hours
• Protocol booklet – reference values provided (click here)
• Species: Rat
• Alternative Names: N-terminal pro-brain natriuretic peptide, NT-proBNP
• For Research Use Only
• Control included, color coded reagents

 

Product Citations: 

–Circulating mitochondria carrying cGAS promote endothelial Secreted group IIA phospholipase A2-mediated neuroinflammation through activating astroglial/microglial Integrin-alphavbeta3 in subfornical organ to augment central sympathetic overdrive in heart failure rats. Zhang S, Huang Y, Han C, Chen M, Yang Z, Wang C. Int Immunopharmacol. 2025 Jan 10;144:113649. doi: 10.1016/j.intimp.2024.113649. Epub 2024 Nov 24. PMID: 39586230.

Snippet: C-1 (C2006), MitoTracker Green (C1048), and MitoTracker Red (C1049) were purchased from Beyotime (Shanghai, China). The rat NT-proBNP ELISA Kit (BI-1204R) and rat NE ELISA Assay Kit (EA633/96) were obtained from Eagle Biosciences (Amherst, NH, USA).

–Platelet transfusion induces transfusion-associated circulatory overload in rats with myocardial infarction. Phelp PG, Hurks B, Polet CA, Roelofs JJTH, Tuip-de Boer AM, Kapur R, Vlaar APJ, van den Brom CE, Klanderman RB.Transfusion. 2025 Jul;65(7):1251-1263. doi: 10.1111/trf.18285. Epub 2025 May 19. PMID: 40384327; PMCID: PMC12227162.

 Snippet: N-terminal prohormone of brain natriuretic peptide (NT-proBNP; Cat# BI-1204R, Biomedica, Austria)

–Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition. Alves PKN, Schauer A, Augstein A, Männel A, Barthel P, Joachim D, Friedrich J, Prieto ME, Moriscot AS, Linke A, Adams V. Cells. 2023 Nov 2;12(21):2561. doi: 10.3390/cells12212561. PMID: 37947639; PMCID: PMC10648219.

Snippet: Blood serum was separated by centrifugation, and NT-proBNP levels were measured using RatNT-proBNP ELISA (Biomedica Immunoassays, Vienna, Austria) according to the manufacturer’s protocol.

 

 

Does active Vitamin D prevent bone loss?

Kidney transplant recipients are at increased risk of bone loss due to the effects of medication and metabolic changes. In a study by Khairallah P et al, researchers evaluated whether oral calcitriol (active vitamin D) could help prevent bone loss in patients managed with steroid-free immunosuppression. Sixty-seven patients were randomized to receive either calcitriol or a placebo for 12 months. The results showed no significant differences in bone density, quality, or strength between the two groups. Biochemical markers evolved similarly in both groups as well. However, the incidence of hypercalcemia was higher among those taking calcitriol compared to placebo. The study concluded that calcitriol does not prevent bone loss and may raise the risk of hypercalcemia, suggesting that routine use may not be necessary if vitamin D levels are sufficient.

Osteoporosis after Kidney Transplantation

Calcitriol supplementation after kidney transplantation: results of a double-blinded, randomized, placebo-controlled trial. Khairallah P et al., J Bone Miner Res. 2025 May 24;40(5):603-616. doi: 10.1093/jbmr/zjaf044. PMID: 40089990; PMCID: PMC12103722.

Abstract

A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year posttransplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling. In this double-blind, placebo-controlled trial, 67 participants aged ≥18 yr on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.5 μg or placebo for 12 mo after transplantation. The primary endpoint was the percent change in cortical density at the radius and tibia from pre- to postcalcitriol treatment compared to placebo as measured by HR-pQCT. Areal BMD was measured by DXA. Cortical and trabecular volumetric BMD and microarchitecture and total estimated bone strength were measured by HR-pQCT. Blood samples for bone metabolic markers were obtained at baseline, 1- and 12 mo. All primary analyses were intent to treat. Safety was assessed for hypercalcemia and progression of vascular calcifications. Thirty-two participants received calcitriol and 29 received placebo; 27 and 27 participants completed the study, respectively. Most participants were male and Caucasian. Baseline Z-scores at all sites were within 0.5 SD of the general population. At 12 mo posttransplantation, there were no between-group differences in areal BMD, volumetric BMD, microarchitecture or bone strength, or serum levels of bone markers. Participants with versus without bone loss had a blunted anabolic response over 12 mo measured by serum bone markers. Hypercalcemia was higher in the calcitriol group compared to placebo (p < .001). No changes in arterial calcification scores were observed. In this randomized placebo-controlled study of calcitriol administration in kidney transplant recipients on corticosteroid-sparing immunosuppression, calcitriol did not improve bone quality and strength but was associated with higher rates of hypercalcemia.

One of the biochemical markers analysed in the study above was FGF23, measured with the BIOMEDICA.

FGF23 (C-terminal), #BI-20700 and FGF23 intact ELISA, #BI-20700  

• RELIABLE – validated following international quality guidelines
• CITED in over 80 publications
• EASY – 8 standards and 2 controls included
• For SERUM & PLASMA samples
• HIGH QUALITY guaranteed!

 

 

 

 

Literature

Osteoporosis after kidney transplantation-no place for active vitamin D in the prevention of bone loss. Jørgensen HS, Evenepoel P. J Bone Miner Res. 2025 May 24;40(5):567-568. doi: 10.1093/jbmr/zjaf049. PMID: 40156932.

Bone Disease in Chronic Kidney Disease and Kidney Transplant. Bellorin-Font E, Rojas E, Martin KJ. Nutrients. 2022 Dec 29;15(1):167. doi: 10.3390/nu15010167. PMID: 36615824; PMCID: PMC9824497.

Maintaining strong and healthy bones is crucial for overall well-being. Bones not only provide structural support for the body but also protect vital organs and serve as reservoirs for essential minerals like calcium and phosphorus. Key aspects of bone health include bone density and bone strength.

Osteoporosis is a condition characterized by weakened and fragile bones. It is the most prevalent metabolic bone disorder worldwide and can affect people of all ages, though it is more commonly associated with aging (1). Both men (2) and women can develop osteoporosis, but postmenopausal women are at a higher risk due to declining estrogen levels, which normally help protect bone health (3). Prevention strategies include maintaining a balanced diet and engaging in regular exercise.

Bone remodeling is a continuous, tightly regulated process involving the resorption of old or damaged bone and the formation of new bone tissue. Various hormones and factors influence bone metabolism. The bone cycle encompasses different phases, and markers of bone metabolism can be classified into markers of bone formation, markers of bone resorption, and markers involved in the regulation of bone metabolism.

Biomarkers of bone regulation

Protein biomarkers are frequently utilized in clinical research and practice to evaluate bone health and monitor the effectiveness of osteoporosis treatments. Some of these biomarkers offer insights into the regulatory processes governing bone metabolism and turnover. Measuring these markers can help assess overall bone health. Key regulatory biomarkers include:

Sclerostin (SOST): Produced by osteocytes, the bone cells embedded within bone tissue, sclerostin is a bone-specific inhibitor of the Wnt signaling pathway. It negatively influences bone formation by promoting osteoclastogenesis and increasing bone resorption. Elevated levels of sclerostin may indicate reduced bone formation.

Dickkopf-1 (DKK-1): Similar to sclerostin, DKK-1 inhibits Wnt signaling, which is essential for bone formation. Increased serum DKK-1 levels can promote bone resorption, potentially signaling suppressed bone formation.

The Wnt signaling pathway is one of the most vital mechanisms regulating bone metabolism. Sclerostin and Dickkopf-1 function as inhibitors of Wnt signaling and are essential in the regulation of bone formation and resorption.

 

Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL): A critical regulator of osteoclast development and activation, RANKL promotes bone resorption by stimulating osteoclast activity. It is secreted by osteocytes and plays a central role in osteoclast formation.

Osteoprotegerin (OPG): Serving as a decoy receptor for RANKL, OPG modulates bone resorption. The ratio of OPG to RANKL influences bone remodeling processes, with alterations potentially impacting bone strength.

Fibroblast Growth Factor 23 (FGF23): This hormone regulates phosphate balance and vitamin D metabolism. Abnormal FGF23 levels are linked to bone disorders such as hypophosphatemic rickets, which can impair bone health.

 

These biomarkers can easily be measured in human blood samples with an ELISA assay

 

Sclerostin (SOST) ELISA  (BI-20492)

• • Most internationally referenced Sclerostin ELISA with more than 320 citations
  • Low sample volume – 20µl / well
  • Full validation package

 

Bioactive Sclerostin ELISA (BI-20472)

• • Targets the receptor binding region
  • Full validation package
  • Low sample volume – 20 µl of serum/plasma per well 

 

Dickkopf-1 (DKK-1) ELISA  (BI-20413)

• • Widely cited +180 publications
  • Direct measurement
  • Validated following international quality guidelines

 

Osteoprotegerin (OPG) ELISA (BI-20403)

• • most referenced human OPG ELISA in +280 citations
  • day test, ready to use color coded reagents
  • controls included

 

Free soluble RANKL ELISA (BI-20462)

• • Highly sensitive  – measurable concentrations in healthy subjects
  • Only assay measuring free, uncomplexed soluble RANKL
  • Cited in over +320 citations 

 

FGF23 c-terminal multi-matrix ELISA (BI-20702)

• • for serum and plasma samples
  • full validation package 
  • cited in +60 publications

 

FGF23 intact ELISA (BI-20700)

• • for serum and plasma samples
  • full validation package
  • one-step ELISA

 

Literature 

1. Bone Health and Osteoporosis Prevention and Treatment. Muñoz M, Robinson K, Shibli-Rahhal A.Clin Obstet Gynecol. 2020 Dec;63(4):770-787. doi: 10.1097/GRF.0000000000000572. PMID: 33017332.
2. Osteoporosis in men. Lancet Diabetes Endocrinol. Vilaca T, Eastell R, Schini M. 2022 Apr;10(4):273-283. doi: 10.1016/S2213-8587(22)00012-2. Epub 2022 Mar 2. PMID: 35247315.
3. Postmenopausal Osteoporosis: A Review of Latest Guidelines. Subarajan P, Arceo-Mendoza RM, Camacho PM. Endocrinol Metab Clin North Am. 2024 Dec;53(4):497-512. doi: 10.1016/j.ecl.2024.08.008. Epub 2024 Oct 5. PMID: 39448132.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the primary cause of cognitive decline among older adults (1). In 2019, 55 million people were estimated to have dementia across the world, a figure predicted to increase to 139 million by 2050 according to the WHO (2).

Advancing age is a significant risk factor for both osteoporosis and Alzheimer’s disease (AD) as individuals with osteoporosis are more susceptible to developing AD later in life (3). Recent research has uncovered a connection between Alzheimer’s disease (AD) and osteoporosis (OP), emphasizing overlapping pathological characteristics that suggest they may share common regulatory and pathogenic mechanisms (4). It has been suggested that bone tissue can influence the function of other organs through the secretion of various proteins into the bloodstream (5).  Brain and bone tissues can regulate each other in different manners through bone-brain axis (3).

Bone derived SCLEROSTIN is associated with Alzheimer´s Disease

Alzheimer’s disease and Wnt Signaling

The Wnt signaling pathway plays a critical role in embryonic development and adult tissue homeostasis. This pathway also is vital in brain development and maintenance. Studies have shown that in AD, Wnt signaling is often dysregulated, and its deficiency can contribute to synaptic degeneration and cognitive decline (6, 7). 

Alzheimer’s disease and Sclerostin

Sclerostin (SOST) is a protein secreted by osteocytes, bone cells embedded in the bone tissue. Sclerostin is a key inhibitor of Wnt/β-catenin signaling. Increased sclerostin levels, often observed with aging, are linked to a higher accumulation of amyloid-beta (Aβ) and cognitive decline in both Alzheimer’s disease patients and older adults (8). In a mouse model researchers also demonstrated that osteocyte-derived sclerostin crosses the blood–brain barrier of old mice, where it dysregulates Wnt–β-catenin signalling (9).

Proposed Mechanism

Sclerostin’s inhibition of Wnt/β-catenin signaling can lead to increased BACE1 activity, which is involved in the production of Aβ, a key protein that forms plaques in the brains of AD patients (10). 

Therapeutic Implications

Understanding the role of sclerostin in AD has led to the exploration of strategies to target the Wnt pathway or sclerostin itself, potentially as a therapeutic approach for AD (9). 

Sclerostin ELISA, #BI-20492 developed and manufactured by BIOMEDICA

• TRUSTED – most referenced Sclerostin ELISA (+320 citations)
• LOW sample volume – 20µl sample /well
•  
• For SERUM & PLASMA samples
• RELIABLE – validated  following international quality guidelines

 

 

Also available:

 Bioactive Sclerostin ELISA, BI-20472

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• EXTENSIVELY validated for clinical samples
• LOW sample volume – 20µl sample /well 

 

Literature

1. Worlds Alzheimer´s Report 2024 , Alzheimer’s Disease International. 2024. World Alzheimer Report 2024: Global changes in attitudes to dementia. London, England: Alzheimer’s Disease International.
2. Ageing and Health, World Health Organization.
3. Research progress in Alzheimer’s disease and bone-brain axis. Zhang F, Zhang W. Ageing Res Rev. 2024 Jul;98:102341. doi: 10.1016/j.arr.2024.102341. Epub 2024 May 15. PMID: 38759893.
4. The potential link between the development of Alzheimer’s disease and osteoporosis. Nasme F, Behera J, Tyagi P, Debnath N, Falcone JC, Tyagi N. Biogerontology. 2025 Jan 20;26(1):43. doi: 10.1007/s10522-024-10181-z. PMID: 39832071; PMCID: PMC12087362.
5. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS. Biomed Res Int. 2015;2015:421746. doi: 10.1155/2015/421746. Epub 2015 Jul 13. PMID: 26247020; PMCID: PMC4515490.
6. The role of Wnt signaling in the development of Alzheimer’s disease: a potential therapeutic target? Biomed Res Int. 2014;2014:301575. Wan W, Xia S, Kalionis B, Liu L, Li Y. doi: 10.1155/2014/301575. Epub 2014 May 4. PMID: 24883305; PMCID: PMC4026919.
7. Wnt Signaling Deregulation in the Aging and Alzheimer’s Brain. Front Cell Neurosci. Palomer E, Buechler J, Salinas PC. 2019 May 22;13:227. doi: 10.3389/fncel.2019.00227. PMID: 31191253; PMCID: PMC6538920.
8. Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults. Yuan J, Pedrini S, Thota R, Doecke J, Chatterjee P, Sohrabi HR, Teunissen CE, Verberk IMW, Stoops E, Vanderstichele H, Meloni BP, Mitchell C, Rainey-Smith S, Goozee K, Tai ACP, Ashton N, Zetterberg H, Blennow K, Gao J, Liu D, Mastaglia F, Inderjeeth C, Zheng M, Martins RN. NPJ Aging. 2023 Sep 4;9(1):17. doi: 10.1038/s41514-023-00114-4. PMID: 37666862; PMCID: PMC10477312.
9. Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer’s disease progression. Shi T, Shen S, Shi Y, Wang Q, Zhang G, Lin J, Chen J, Bai F, Zhang L, Wang Y, Gong W, Shao X, Chen G, Yan W, Chen X, Ma Y, Zheng L, Qin J, Lu K, Liu N, Xu Y, Shi YS, Jiang Q, Guo B. Nat Metab. 2024 Mar;6(3):531-549. doi: 10.1038/s42255-024-00989-x. Epub 2024 Feb 26. PMID: 38409606.
10. The Alzheimer’s disease beta-secretase enzyme, BACE1. Cole SL, Vassar R. Mol Neurodegener. 2007 Nov 15;2:22. doi: 10.1186/1750-1326-2-22. PMID: 18005427; PMCID: PMC2211305.
11. Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid-beta (Abeta)42 peptides. Tapia-Rojas C, Burgos PV, Inestrosa NC. J. Neurochem. 2016;139

 

Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults. Yuan J et al., Aging. 2023.  

Abstract

Osteoporosis and Alzheimer’s disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into Aβ- (n = 65) and Aβ+ (n = 35) according to their brain Aβ load assessed using Aβ-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including Aβ40, Aβ42, Aβ42/Aβ40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the Aβ+ group (71.49 ± 25.00 pmol/L) compared with the Aβ- group (56.51 ± 22.14 pmol/L) (P < 0.01). Moreover, Spearman’s correlation analysis showed that plasma SOST concentrations were positively correlated with brain Aβ load (ρ = 0.321, P = 0.001). Importantly, plasma SOST combined with Aβ42/Aβ40 ratio significantly increased the area under the curve (AUC) when compared with using Aβ42/Aβ40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD. 

 

Lyme disease or Lyme Borreliosis is a bacterial infection that is spread to humans by infected ticks (1). It is the most common tick-transmitted infection in temperate zones of the northern hemisphere. Symptoms include fever, headache, fatigue, and an expanding skin rash.  If left untreated, the infection can spread to various parts of the body, affecting joint, heart, and the nervous system. Early diagnosis and treatment are essential for effectively managing Lyme Borreliosis. In a recent investigators highlight notable neurological and musculoskeletal complications in patients with Lyme disease, underscoring the critical need for early diagnosis, thorough treatment, and supportive care (2) .

Lyme Disease Testing

BIOMEDICA´s BORRELIA ELISA kits utilize recombinant antigens for the detection of IgG and IgM antibodies against the immunodominent antigens of the three genospecies: Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii

Features include:

• High sensitivity and specificity confirmed by clinical samples
• Use of different immunodominant antigens for the early and late phase
• CE -marked for IVD use in the EU
• For manual and automated testing
• Cited in numerous publications

 

 

Borrelia IgM ELISA ▪ BI-21042

ENZYME-LINKED IMMUNOSORBANT ASSAY FOR THE QUALITATIVE OR QUANTITATIVE DETERMINATION OF IgM ANTIBODIES TO BORRELIA IN PLASMA, SERUM OR CEREBROSPINAL FLUID

Recombinant antigens utilized in the Biomedica Borrelia IgM ELISA Assay:

• p21  OspC – B. afzellii (pKo)
• p21  OspC – B. garinii (20047)
• p41/I – B. bavariensis (pBi)
• VIsE – fusion proteins of different Borrelia genospecies 

More information can be found in the protocol booklet here

Borrelia IgG ELISA ▪ BI- 21032

ENZYME-LINKED IMMUNOSORBANT ASSAY FOR THE QUALITATIVE OR QUANTITATIVE DETERMINATION OF IgG ANTIBODIES TO BORRELIA IN PLASMA, SERUM OR CEREBROSPINAL FLUID

Recombinant antigens utilized in the Biomedica Borrelia IgG ELISA Assay:

• p21 – OspC – B. burgdorferi sensu stricto (B31), B. garinii (20047)
• p18 – B. afzelii (pKo)
• p100 – B. afzelii (pKo)
• VIsE – fusion protein of different Borrelia genospecies

More information can be found in the protocol booklet here

 

Literature

1. Lyme Disease. Ann Intern Med. Smith RP. 2025; 178(5):ITC65-ITC80. doi: 10.7326/ANNALS-25-01111. PMID: 40354663.
2. Lyme disease associated neurological and musculoskeletal symptoms: A systematic review and meta-analysis. Bushi G, Balaraman AK, Gaidhane S, Ballal S, Kumar S, Bhat M, Sharma S, Kumar MR, Sinha A, Khatib MN, Rai N, Sah S, Yappalparvi A, Samal SK, Lingamaiah D, Shabil M. Brain Behav Immun Health. 2025; 2;43:100931. doi: 10.1016/j.bbih.2024.100931. PMID: 39867846.
3. Seroprevalence of Borrelia, Anaplasma, Bartonella, Toxoplasma, Mycoplasma, Yersinia, and Chlamydia in Human Population from Eastern Poland. Wójcik-Fatla, A.; Sawczyn-Domańska, A.; Kloc, A.; Krzowska-Firych, J.; Sroka, J. Pathogens 2025, 14, 96.

Chronic kidney disease (CKD) is a major global health concern, affecting roughly 10 percent of the population, totaling more than 850 million people (1, 2).

CKD involves progressive nephron loss, compensatory hyperfiltration in remaining nephrons, and subsequent glomerulosclerosis (3, 4). This process is often driven by etiologies such as diabetic nephropathy (5), glomerulonephritis, and other systemic or intrinsic renal diseases.

Biochemical hallmarks include decreased clearance of nitrogenous waste products such as urea and creatinine, leading to azotemia (6). The disruption of electrolyte homeostasis may result in hyperkalemia, metabolic acidosis, and disturbances in calcium-phosphate balance, contributing to secondary hyperparathyroidism and vascular calcification (7).

CKD progression is associated with increased cardiovascular morbidity and mortality (8).The disease course can be monitored via estimated glomerular filtration rate (eGFR), albuminuria levels, and imaging findings of renal morphology (9).

Role of the Kidneys

Kidneys are vital organs that regulate fluid balance, blood pressure and produce hormones that stimulate the production of red blood cells . Kidney disease is a condition in which kidneys lose their ability to effectively filter waste products and excess fluids from the blood. Kidney disease commonly leads to a decline in kidney function that may lead to kidney failure, characterized by the complete loss of kidney function. At this stage dialysis or kidney transplantation become the only treatment option.

Kidney problems can emerge suddenly (acute) or gradually over time (chronic). Various conditions, diseases and medications can contribute to acute and chronic kidney problems.  Chronic kidney disease (CKD) is characterized by a prolonged period of kidney abnormalities that last for more than three months (10), whereas acute kidney disease – acute kidney injury (AKI) is characterized by a sudden loss of excretory kidney function (11).

Other forms of kidney disease include polycystic kidney disease (PKD) a genetic disorder that leads to kidney enlargement and impaired kidney function over time and glomerulonephritis (GN) (12). GN is a group of diseases characterized by inflammation of the glomeruli, the filtration units of the kidney (13).

Novel Biomarkers in Nephrology

FGF23  •  SCLEROSTIN  •  ENDOSTATIN  •  VANIN-1  •  PERIOSTIN

Advancements in nephrology have led to the identification of several emerging biomarkers that enhance early detection, prognosis, and understanding of kidney injury and disease progression. These novel biomarkers could provide more sensitive and specific insights compared to traditional measures like serum creatinine and albuminuria.

FGF23  – in Acute Kidney Injury

Fibroblast growth factor 23 (FGF23) is a hormone produced by bone that plays a key role in regulating phosphate excretion by the kidneys. In the context of kidney disease, declining renal function leads to an increase in serum phosphate levels, which in turn stimulates the secretion of FGF23. Elevated phosphate levels are also frequently observed in patients with acute kidney injury (AKI) (14).

FGF23 as a Marker of Adverse Outcomes in AKI

Levels of FGF23 rise rapidly during AKI and have been associated with the need for renal replacement therapy (14-17). Furthermore, FGF23 levels possess prognostic value, as demonstrated in a large study  in over 1500 patients with AKI (16).

FGF23 and Sclerostin – Novel Biomarkers in Diabetic Kidney Disease

Growing evidence indicates that FGF23 may be involved in type 2 diabetes (T2DM), as levels of FGF23 are elevated in these patients—even among those with normal kidney function—when compared to the general population (18). A recent study demonstrated phosphate-independent effects of FGF23 following glucose loading, showing associations between FGF23 and levels of glucose, insulin, and proinsulin, as well as obesity (19). Additionally, FGF23 has been linked to the development of gestational diabetes mellitus (20).

Sclerostin is a protein produced by bone cells that inhibits bone formation. Recent research suggests that sclerostin also influences lipid and glucose metabolism, as serum sclerostin levels are negatively associated with insulin sensitivity in obese women, but not in lean women (21). Elevated sclerostin levels have also been observed in individuals with prediabetes (22).

 FGF23 and Sclerostin can reliable by measured with conventional ELISA assays from BIOMEDICA.

• FGF23 (C-terminal) |BI-20700 and FGF23 intact ELISA |BI-20700               
• Sclerostin ELISA |BI-20492 and Bioactive Sclerostin ELISA |BI-20472    

 

Endostatin – A Potential Biomarker for Renal Fibrosis, CKD, and Prognosis in AKI

Endostatin is a protein found in the extracellular matrix that is expressed during the progression of renal fibrosis. Elevated serum levels of endostatin may result from increased degradation of the extracellular matrix in patients with chronic kidney disease (CKD) (23, 24). Additionally, endostatin has been explored as a prognostic marker in individuals with acute kidney injury (AKI) (25) and has been independently linked to the occurrence of cardiovascular events in CKD patients (26).

Endostatin can reliably be quantified in serum, plasma and urine samples:

• Endostatin ELISA | BI-20742

 

VANIN-1 – A Potential Biomarker for Acute Kidney Injury and Drug-Induced Renal Injury

Vascular non-inflammatory molecule-1 (Vanin-1) is highly expressed in the kidney (27) and has been proposed as a biomarker for acute kidney injury (AKI) and drug-induced renal damage (28). It has also been identified as an indicator of kidney injury in a rat model of type 1 diabetic nephropathy (29).

Urinary Vanin-1 has been studied in children with renal fibrosis (30) and as a potential predictor of acute pyelonephritis in young children with urinary tract infections (31). More recently, research has explored the role of urinary Vanin-1 in kidney transplant recipients (32).

Vanin-1 can easily be measured with a conventional ELISA assay:

• Vanin-1 (urine) ELISA | BI-VAN1U  (33)

 

PERIOSTIN – A Potential Early Biomarker of Renal Tubular Injury

Periostin is a matricellular protein involved in tissue remodeling and wound healing processes. Research has shown that Periostin expression in the kidney correlates with the extent of interstitial fibrosis and a decline in renal function (34). Elevated levels of urinary Periostin have been observed in patients with type 2 diabetes, even before the appearance of microalbuminuria. These findings suggest that urinary Periostin may serve as an early marker of renal tubular injury (35).

Periostin can be accurately measured in serum, plasma, and urine through a fully validated ELISA assay (36).

• Periostin ELISA | BI-20422

 

BIOMEDICA – HIGH QUALITY ASSAYS – Fully validated according to international quality guidelines

• TRUSTED – Widely cited in over 1800 publications

 

 

See our brochure on Biomarkers in Clinical Nephrology  

 

Literature

1. ISN- International Society of Nephrology
2. Global Facts: About Kidney Disease
3. Remnant nephron physiology and the progression of chronic kidney disease. Schnaper HW. Pediatr Nephrol. 2014; 29(2):193-202.  PMID: 23715783.
4. Mechanisms of progression of chronic kidney disease. Fogo AB. Pediatr Nephrol. 2007;  22(12):2011-22. PMID: 17647026.
5. Classification and Differential Diagnosis of Diabetic Nephropathy. Qi C et al.,  J Diabetes Res. 2017; 2017:8637138. PMID: 28316995.
6. Azotemia. Tyagi A, Aeddula NR. 2023;  In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30844172.
7. Understanding Vascular Calcification in Chronic Kidney Disease: Pathogenesis and Therapeutic Implications. Siracusa C et al., Int J Mol Sci. 2024; 25(23):13096. PMID: 39684805.
8. The Dual Burden: Exploring Cardiovascular Complications in Chronic Kidney Disease. Biomolecules. Caturano A et al., 2024: 14(11):1393. PMID: 39595570.
9. The KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD), 2024. Chronic Kidney Disease Diagnosis and Management: A Review. Chen TK, Knicely DH, Grams ME. JAMA. 2019 Oct 1;322(13):1294-1304. doi: 10.1001/jama.2019.14745. PMID: 31573641; PMCID: PMC7015670.
10. Chronic Kidney Disease Diagnosis and Management: A Review. Chen TK et al.,  JAMA. 2019; 322(13):1294-1304.  PMID: 31573641.
11. Acute kidney injury. Kellum JA et al.,. Nat Rev Dis Primers. 2021; 15;7(1):52. PMID: 34267223.  
12.  Treatment of Autosomal-Dominant Polycystic Kidney Disease. Jdiaa SS et al.,. Am J Kidney Dis. 2025; 85(4):491-500.  PMID: 39424253.
13. Advances in primary glomerulonephritis. Ellison B et al.,  J Hosp Med (Lond). 2024; 30;85(7):1-11. PMID: 39078905.
14. Fibroblast Growth Factor 23 and Klotho in AKI. Christov M, Neyra JA, Gupta S, Leaf DE. Semin Nephrol. 2019 Jan;39(1):57-75. doi: 10.1016/j.semnephrol.2018.10.005. PMID: 30606408. 
15. Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury. Zhou W et al.,  Nephron. 2022;146(3):239-242. PMID: 34284404. 
16. Fibroblast growth factor 23 associates with death in critically ill patients. Leaf DE et al., Am Clin J Am Soc Nephrol. 2018. 13(4):531–41. 
17. FGF-23 levels in patients with AKI and risk of adverse outcomes. Leaf DE et al., Clin J Am Soc Nephrol. 2012. 7(8):1217-23. 
18. Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease Wahl P et al. 2012.  Diabetes Care 35, 994–1001.  
19. Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies, Amarens van der Vaart et al., 2023. The Journal of Clinical Endocrinology & Metabolism,  108, 10,  e971–e978.
20. Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF et al., Diabetes Metab Res Rev. 2023. 8:e3704. PMID: 37553983.
21. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A et al., Endocr Connect. 2021. 10(2):131-138. PMID: 33480863.
22. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G et al., Diabetes Care. 2015. 38(8):1509-17.  PMID: 26084344.
23. A defective angiogenesis in chronic kidney disease. Futrakul N et al., Ren Fail. 2008. 30(2):215-7.  PMID: 18300124.
24. Endostatin in Renal and Cardiovascular Diseases. Li M et al., Kidney Dis (Basel). 2021.9;7(6):468-481. PMID: 34901193.
25. Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study. Jia HM et al.,  J Int Med Res. 2020.  48(7):300060520940856. PMID: 32691651.
26. Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Kanbay M et al., Eur J Intern Med. 2016. 33:81-7.  PMID: 27394925.
27. Chemical biology tools to study pantetheinases of the vanin family. Schalkwijk, J, Jansen, P. Biochem Soc Trans. 2014. 42, 1052–1055.
28. Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury. Hosohata K et al.J  Pharm  Exp Ther. 2012. 341, 656–662.
29. Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. Fugmann T et al., Kidney Int. 2011. 80, 272–281.
30. The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study. Mizerska-Wasiak M et al.,  J Clin Med. 2022. 11(5):1265. PMID: 35268356. 
31. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G et al., Biomarkers. 2021. 26(4):318-324.
32. Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients. Alkaff FF et al., Sci Rep. 2024. 4(1):2283.  PMID: 38280883.
33. Development of an immunoassay that reveals altered uninary Vanin-1 in human with kidney disease. Wallwitz, J.,  et al.,. 2018. Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, Page i126. 
34. Periostin in the Kidney. Wallace DP et al., Adv Exp Med Biol. 2019, 1132:99-112.
35. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus. Satirapoj B et al., PLoS One. 2015, 17;10(4):e0124055.
36. Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018, 32(2):e22252.

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare hereditary bone disorder with an estimated incidence of about 1 in 10,000 to 1 in 20,000 (1). It is characterized by low bone mass, increased bone fragility and recurrent fractures. The condition results from mutations that disrupt the synthesis and post-translational modification of type I collagen. Recent research indicates that the severity of OI phenotypes is influenced not only by abnormalities in type I collagen metabolism but also by alterations in osteoblast function (2), although the underlying mechanisms remain unclear. So far, none of the current available treatments have shown an overall efficacy in treating OI, thus demonstrating the unmet clinical need for managing OI (3). A recent study in mice has shown that  DKK1-antisense treatment can improve bone mechanical strength, restore the expression of osteogenic genes, stimulate osteogenesis, and suppress osteoclastogenesis in OI mice (3).

 

The Wnt/β-catenin pathways plays a key role in the regulation of osteogenesis. Dickkopf-1 (DKK-1) is a direct inhibitor of Wnt/β-catenin signaling by binding with high affinity to LRP5/LRP6 and Kremen proteins, inhibiting osteoblast function and bone formation. It is a soluble protein secreted in the bone microenvironment and can be detected in the circulation. In a recent study researchers measured DKK-1 concentrations in children with OI and examined its association with bone mineral density (BMD), fracture frequency, bone turnover markers, and the underlying genetic mutations of OI (4).

DKK-1 a potential biomarker and therapeutic target in Osteogenesis Imperfecta                                      

Key findings:

– concentrations were significantly higher in children with OI compared to healthy children

– DKK-1 is closely correlated to the skeletal phenotype of children with OI

– DKK-1 may become a novel biomarker and a potential therapeutic target of OI

 

Biomedica´s high quality human DKK-1 ELISA cat. no. BI-20413

• widely cited in over 180 publications
• day test
• no sample dilution
• full validation package

 

Related Products: SCLEROSTIN ELISA (BI-20492), BIOACTIVE SCLEROSTIN ELISA (BI-20472)

 

Correlation of serum DKK1 level with skeletal phenotype in children with osteogenesis imperfecta.  Wang Y et al., J Endocrinol Invest. 2024

Abstract

Purpose: We aim to detect serum DKK1 level of pediatric patients with OI and to analyze its relationship with the genotype and phenotype of OI patients.

Methods: A cohort of pediatric OI patients and age-matched healthy children were enrolled. Serum levels of DKK1 and bone turnover biomarkers were measured by enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry. Pathogenic mutations of OI were detected by next-generation sequencing and confirmed by Sanger sequencing.

Results: A total of 62 OI children with mean age of 9.50 (4.86, 12.00) years and 29 healthy children were included in this study. The serum DKK1 concentration in OI children was significantly higher than that in healthy children [5.20 (4.54, 6.32) and 4.08 (3.59, 4.92) ng/mL, P < 0.001]. The serum DKK1 concentration in OI children was negatively correlated with height (r = – 0.282), height Z score (r = – 0.292), ALP concentration (r = – 0.304), lumbar BMD (r = – 0.276), BMD Z score of the lumbar spine and femoral neck (r = – 0.32; r = – 0.27) (all P < 0.05). No significant difference in serum DKK1 concentration was found between OI patients with and without vertebral compression fractures. In patients with spinal deformity (22/62), serum DKK1 concentration was positively correlated with SDI (r = 0.480, P < 0.05). No significant correlation was observed between serum DKK1 concentration and the annual incidence of peripheral fractures, genotype and types of collagen changes in OI children.

Conclusion: The serum DKK1 level was not only significantly elevated in OI children, but also closely correlated to their skeletal phenotype, suggesting that DKK1 may become a new biomarker and a potential therapeutic target of OI.

Literature

1. Osteogenesis imperfecta: an update on clinical features and therapies. Marom R, Rabenhorst BM, Morello R. Eur J Endocrinol. 2020; 83(4):R95-R106. PMID: 32621590.
2. Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical and Rare OI Types. Jovanovic M, Guterman-Ram G, Marini JC. Endocr Rev. 2022; 43(1):61-90. PMID: 34007986.
3. Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease. Ko JY, Wang FS, Lian WS, Yang FS, Chen JW, Huang PH, Liao CY, Kuo SJ. Mol Med. 2024; 30(1):66. PMID: 38773377; PMCID.
4. Correlation of serum DKK1 level with skeletal phenotype in children with osteogenesis imperfecta. Wang Y, Hu J, Sun L, Zhou B, Lin X, Zhang Q, Wang O, Jiang Y, Xia W, Xing X, Li M. J Endocrinol Invest. 2024; 47(11):2785-2795. PMID: 38744806.

.

We are excited to be soon attending the ECTS Congress in Innsbruck, Austria from May 23-26, 2025. Meet us at our banner exhibition “Biomedica´s Bone Marker ELISAs” and explore our kits including SCLEROSTIN, OPG, RANKL, FGF23, PERIOSTIN, and many others.

We look forward to connecting with you!

Join us at ECTS 

Click here for more information about the congress.

The ECTS 2025 Congress is recognized as the premier annual gathering in Europe dedicated to this field. The congress offers a comprehensive and engaging scientific program that covers the most recent advances, challenges, and debates related to bone and calcified tissues. The program aims to unite researchers,  clinicians, and health professionals, showcasing their latest research.

Biomarkers in Bone Biology
Bone cells produce biomarkers throughout the process of bone remodeling. These biomarkers are valuable for evaluating bone diseases and serve as potential therapeutic targets. They can be readily identified in serum and plasma samples using immunoassay techniques.

A recent review by Fernández-Villabrille S et al.,  Novel Biomarkers of Bone Metabolism explores some emerging biomarkers in mineral and bone metabolism like:

Receptor Activator of NFkappa B lingand (RANKL), Osteoprotegerin (OPG), Sclerostin (SOST), Dickkopf-1 (DKK-1), Periostin (POSTN) and others.

 

BIOMEDICA offers quality Bone Marker ELISA assay kits: 

-Sclerostin ELISA (SOST; cat.no. BI-20492)  

-OPG ELISA (Osteoprotegerin; cat.no. BI-20403)  

-RANKL ELISA (soluble RANKL; cat.no. BI-20462)  

-DKK-1 ELISA (Dickkopf-1; cat.no. BI-20413)  

-FGF23 intact ELISA (Fibroblast growth factor-23 intact; cat.no. BI-20700) 

-FGF23 C-terminal ELISA  (Fibroblast growth factor-23 C-terminal; cat.no. cat.no. BI-20702) 

-PERIOSTIN ELISA (POSTN, BI-20433) 

-NT-proCNP ELISA (NT-C-type natriuretic peptide, BI-20812)

 

 TRUSTED – cited in over 1300 publications

• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria

 

About SCLEROSTIN

Sclerostin (SOST), primarily produced by osteocytes, is regarded as a key regulator of bone formation. It functions as a soluble antagonist of the Wnt signaling pathway. Inhibition of this pathway results in bone resorption, whereas activation of Wnt signaling stimulates bone formation.

About PERIOSTIN

Periostin (POSTN) is an extracellular matrix protein predominantly expressed in the periosteum, the membrane covering the outer surface of bones that plays a role in bone growth. It is involved in various processes, including bone biology, tissue repair, cancer, cardiovascular and respiratory conditions, as well as in numerous inflammatory conditions such as asthma.

Sclerostin is an osteocyte-derived secreted glycoprotein that suppresses bone formation.  Our Sclerostin ELISA assay was highlighted in a recent study investigating the effect of vitamin D3, omega-3 fatty acids (omega-3s), and exercise on serum sclerostin levels and bone turnover markers. The researchers evaluated the effects of vitamin D3, omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels (1).

 

Sclerostin decreases through exercise and omega-3s

Key findings

Effect of vitamin D3, omega-3 fatty acids, and exercise on serum sclerostin levels and bone turnover markers. Tsourdi E et al., (1)

-In the 3-year prevention trial among largely vitamin D replete adults age 70 and older, structured home-based exercise program (SHEP) alone or in combination with omega-3s reduced serum sclerostin levels, while vitamin D3 and omega-3s alone had no effect on sclerostin levels.

-Omega-3s plus SHEP led to a greater decrease in sclerostin levels compared to no omega-3s/control exercise.

– The bone turnover markers P1NP and β-CTx showed no significant effects for any of the individual treatments and treatment combinations.

 

Biomedica´s SCLEROSTIN  ELISA (cat. no. BI-20492) kit features

• TRUSTED – most referenced Sclerostin ELISA (+320 citations)
• EFFICIENT – 20µl sample /well
• EASY HANDLING: 7 standards and 2 controls

 

About Sclerostin  

Sclerostin is a protein encoded by the SOST gene,  that is mainly produced by osteocytes which are bone cells embedded within the bone matrix. Sclerostin inhibits canonical Wnt signaling, a pathway promoting bone formation Sclerostin acts as a negative regulator of bone formation.

 

Literature

1. Effect of vitamin D3, omega-3 fatty acids, and exercise on serum sclerostin levels and bone turnover markers. Tsourdi E, Gängler S, Kistler-Fischbacher M, Rauner M, Dawson-Hughes B, Orav EJ, Tsai LT, Lang W, Kanis JA, Theiler R, Egli A, Bischoff-Ferrari HA, Hofbauer LC. J Clin Endocrinol Metab. 2024 Dec 9: dgae859. doi: 10.1210/clinem/dgae859. Epub ahead of print. PMID: 39657964.

 

Abstract

Context: Sclerostin inhibits canonical Wnt signaling, a pathway promoting bone formation. The effects of vitamin D3, omega-3 fatty acids (omega-3s), and exercise on serum sclerostin levels and bone metabolism are unclear.

Objective: To investigate the effects of 2000 IU/d vitamin D3, 1g/d omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels.

Design, setting and participants: Sclerostin, procollagen type 1 N propeptide (P1NP) and C-terminal telopeptide (β-CTx) levels were pre-defined secondary outcomes of DO-HEALTH, a double blind, randomized controlled trial in healthy physically active older adults in five European countries.

Outcome measures: Changes in yearly serum sclerostin, P1NP and β-CTx levels over 3 years, adjusted for age, sex, prior falls, study site, baseline BMI, and baseline level of the respective outcome.

Results: 1,848 participants were included (mean age 74.8 ± 4.4 years, 58.9 % women, 41.4 % 25(OH)D < 20 ng/mL, 83.9 % at least moderately physically active at baseline). Vitamin D3 and omega-3s supplementation alone did not change sclerostin levels significantly, while SHEP compared with control exercise (joint mobility) led to greater decrease in sclerostin levels [-1.56 pmol/L (-2.54, -0.58), p=0.002]. Omega-3s plus SHEP led to a greater decrease in sclerostin levels compared to no omega-3s/control exercise [-1.93pmol/L (-3.31, -0.54), p=0.007]. For P1NP and β-CTx there were no significant effects for any of the individual treatments and treatment combinations.

Conclusions: In this 3-year prevention trial among largely vitamin D replete adults age 70 and older, SHEP alone or in combination with omega-3s reduced serum sclerostin levels, while vitamin D3 and omega-3s alone did not affect serum sclerostin levels.

 

 

Osteoporosis is a bone disease characterized by progressive loss of bone density, leading to an increased risk of fractures, particularly in the hip, spine, and wrist. It occurs when the balance between bone resorption and bone formation is disrupted, often due to factors such as aging, hormonal changes (especially post-menopause in women), nutritional deficiencies (such as calcium and vitamin D), sedentarism, and certain medications or medical conditions (1).

The prevalence of osteoporosis among older adults is significant: it is estimated that over 200 million people suffer from osteoporosis worldwide, with about one in three women and one in five men over the age of 50 experiencing an osteoporotic fracture in their lifetime (1). Osteoporosis represents a major public health concern due to its impact on mobility, quality of life, and healthcare costs associated with fracture management and treatment. Surprisingly, in women over 45 years of age, osteoporosis accounts for more days in hospital than may other diseases, including diabetes, myocardial infarction and breast cancer (3).

Bone Health and Osteoporosis

How can Osteoporosis be prevented ?

Regular exercise and a healthy diet, including the intake of key nutrients like Vitamin D and Calcium, are some key factors that can help in preventing the disease (2).

–Calcium: a healthy adult body contains around 1 kg of calcium, 99% of which is deposited in bone and teeth (4). Good sources of calcium include dairy products, leafy green vegetables, fortified foods, and fish with bones (1).

–Vitamin D: vitamin D plays an important role in regulating calcium and maintaining bone health. Although vitamin D influences various aspects of bone and calcium metabolism, one of its most important functions is the regulation of the efficiency of intestinal calcium (Ca) absorption (5).

The primary source of vitamin D is sunlight; it is synthesized in the skin. The form of vitamin D produced in the skin is known as vitamin D3 (cholecalciferol), while the dietary forms can be either vitamin D3 or a closely related plant-derived compound called vitamin D2 (ergocalciferol). Only a limited number of foods are naturally high in vitamin D. Dietary sources include fatty fish like salmon, sardines, and mackerel, as well as eggs, liver, and in some regions, fortified products such as margarine, dairy items, and cereals. For more information on sources on vitamin D and Vitamin D recommendations : https://www.osteoporosis.foundation/vitamin-d-recommendations.

-Other potentially risk factors for osteoporosis are smoking, alcohol consumption, low or excessive phosphorus intake, protein deficiency or a high-protein diet, excessive consumption of coffee, a sedentary lifestyle or lack of mobility, and insufficient exposure to the sun (6). 

Role of the human skeleton

The human skeleton provides support and structure for the body, protecting vital organs like the brain and heart. It is an important component of the musculoskeletal system, enabling movement. The skeleton also produces blood cells in its bone marrow and stores essential minerals like calcium. The skeleton is  constantly remodeled throughout life, with old bone being broken down and replaced by new tissue to maintain bone mass. This ongoing process of bone resorption and growth is called bone metabolism.

Bone remodeling

Bone remodeling is a continuous and regulated process where various specialized cells primarily osteoclasts breaking down old bone tissue, and osteoblasts building new bone, are involved. These cells constantly interact via factors like osteoprotegerin (OPG) and RANKL (receptor activator of nuclear factor kappa-B ligand) to maintain a healthy balance between bone resorption and bone formation. Imbalances in this process can lead to bone diseases like osteoporosis.  

Bone cells act as endocrine cells, influencing other organs. Osteocytes, the most common bone cell type embedded within the bone, are key regulators of bone formation. They play an important role in bone remodelling and release specific biomarkers such as sclerostin (SOST), fibroblast growth factor 23 (FGF23), and Dickkopf-1 (DKK-1).

 

Biomedica offers a range of ELISA kits to measure bone biomarkers in serum, plasma, and cell cultures

SCLEROSTIN (SOST; cat.no. BI-20492)

OPG  (Osteoprotegerin; cat.no. BI-20403)

RANKL  (soluble RANKL; cat.no. BI-20462)

DKK-1  (Dickkopf-1; cat.no. BI-20413)

FGF23 intact (Fibroblast growth factor-23, intact; cat.no. BI-20700)

FGF23 C-terminal  (Fibroblast growth factor-23, C-terminal; cat.no. cat.no. BI-20702)

PERIOSTIN  (POSTN, BI-20433)

 

• TRUSTED – cited in over 1200 publications
• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria

 

Literature

1. Assessment of osteoporosis at the primary health-care level. WHO Scientific Group Technical Report. Kanis J. 2007  [Accessed 22.02.2019];
2. The clinician’s guide to prevention and treatment of osteoporosis. LeBoff M et al. Osteoporos Int 33, 2049–2102 (2022).
3. The prevalence of vertebral deformity in european men and women: the European Vertebral Osteoporosis Study. O’Neill TW et al., J Bone Miner Res, 1996. 11(7): p. 1010-8.
4. Physiology of Calcium Homeostasis: An Overview. Matikainen N et al., Endocrinol Metab Clin North Am. 2021; 50(4):575-590. PMID: 34774235.
5. Vitamin D-Mediated Regulation of Intestinal Calcium Absorption . Fleet JC. Nutrients. 2022 Aug 16;14(16):3351. PMID: 36014856.
6. Osteoporosis – risk factors, pharmaceutical and non-pharmaceutical treatment. Tański W et al., Eur Rev Med Pharmacol Sci. 2021; 25(9):3557-3566. PMID: 34002830.

 

The Enzyme Linked Immunosorbent Assay (ELISA) is a widely used laboratory technique designed to detect and quantify proteins, hormones, antibodies, and other molecules in samples such as serum, plasma, saliva, urine, or cell culture supernatants. ELISA assays are used in various fields, including clinical diagnostics and research.  

Selecting the right ELISA kit is an important decision that greatly impacts the results of your experiments. By thoughtfully evaluating factors like sensitivity, dynamic range, precision, and workflow you can make a well-informed decision that aligns with your research objectives. Other parameters that are better indicators of ELISA performance should also be considered. These include type of samples to be measured, recovery, dilution linearity and parallelism (%) to measure the target protein in real samples like plasma, serum, or cell culture media.

ELISA Assay Principle

The main principle of an ELISA involves the binding of an antigen (the target molecule) to a specific antibody. The assay is mostly carried out in a 96-well plate that is coated with capture antibodies specific to the target antigen.

 

ELISA Assay Protocol- Example:

1. Coating: The wells of the 96-well ELISA microplate are coated with a specific capture antibody that binds to the target antigen.
2. Sample Addition: The sample containing the target antigen is added to the wells. Antigen present in the sample binds to coated capture antibody.
3. Detection Antibody: A secondary antibody that is linked to an enzyme, is then added to the wells. It binds specifically to the target antigen, forming a sandwich complex (capture antibody- antigen – secondary antibody).  
4. Substrate Addition: A substrate (e.g. TMB Tetramethylbenzidine) is added to the wells. The enzyme catalyzed color change of the substrate is directly proportional to the amount of target protein present in the sample.
5. Signal Measurement: The color change and the intensity of the color is directly proportional to the amount of target antigen in the samples. It is detectable with a standard microtiter plate ELISA reader (spectrophotometer). A dose response curve of the absorbance (optical density, e.g. OD at 450 nm) versus the standard concentration is generated, using the values obtained from the standards (calibrators).

 

ELISA Assay, 96 well microtiter plate

 

How to select the right ELISA kitBefore purchasing an ELISA assay, always read the kit protocol booklet (package insert). This may help to decide if the kit will be suitable for your needs.

Check as follows:

1. ANALYTE

Which protein biomarker will you be measuring? Be sure to use the correct term during your search. Some biomarker proteins have alternative names (e.g. PERIOSTIN or POSTN ELISA (POSTN is the gene that encodes Periostin).

2. SPECIES – SPECIFICITY – CROSS REACTIVITY

Verify if the assay can be used in the respective model you will be measuring- e.g. human, or preclinical samples such as rat, mouse, monkey. Often ELISA kits can be used for various species, due to high homology between species. As an example the biomarker ELISA kit for NT-proANP was developed for measurements in human samples. Due to the high sequence homology between species, the kit is successfully used to measure NT-proANP as a cardiac safety biomarker in various animal models (rat, mouse, rabbit, monkey). 

3. SAMPLE TYPE

Which sample type (matrix) will you be using (e.g. EDTA-plasma, heparin-plasma, citrate-plasma, serum, cell culture supernatants, urine..) ?

Verify if the assay is compatible for your sample type and check the information in the protocol book. Also check if the assay validation was performed in the respective sample type you will be using. These data can often be found on the website of the assay manufacturer.

Important: the analysis of some biomarkers in the “wrong” sample matrix may lead to “false” results due to a matrix effect.

4. SAMPLE VOLUME

Verify the sample volume that will be required per well, consider duplicates when measuring your samples.

5. SENSITIVTY – BIOMARKER CONCENTRATIONS TO BE EXPECTED

The sensitivity of an ELISA assay refers to the lowest limit of detection (LOD) of the protein that can be detected with the antibody pair used in the ELISA kit. The sensitivity depends mainly on the affinity of the solid phase antibody (coating antibody). Therefore, using a high affinity antibody can increase sensitivity.

-Analytical sensitivity – limit of detection (LOD) is the lowest concentration that can be measured (detected) with statistical significance by means of a given analytical procedure. This concentration is calculated as the background +/- 2 standard deviations.

-Functional Sensitivity –  lower limit of detection (LLOQ) is the lowest concentration at which the analyte can be reliably detected.

How to select the right ELISA kit – before selecting an assay, study the validation data provided in the protocol booklet.

Some companies document the data on their respective website- product page. Documented reference values in an apparently healthy cohort and/or pathological values in serum and/or plasma of the analyte of interest may also be helpful to get an idea in which range sample values can be expected. It will be helpful to know which levels of the target protein can be expected in your respective sample. Sometimes samples require a pre-dilution step to assure that the signal falls within the dynamic range of the assay. Check the information in the protocol booklet if samples require a pre-dilution step and if the dilution buffer is included in the kit.

Of note: assays offering high sensitivity offer a different dynamic range than assays with a lower sensitivity.

    6. DYNAMIC RANGE

The dynamic range if an ELISA refers to the upper and lower range of concentrations of the target protein that the assay can accurately quantify.

Of note: the reported values given for the sensitivity and dynamic range of an assay can be misleading because they are often determined by using the standard protein (calibrators) in a assay buffer. However, this often does not represent the kinetic of detection of an endogenous protein /analyte in the biological sample.

7. ACCURACY / RECOVERY

The accuracy of an ELISA assay correctly identifies the presence or absence of the target protein/antigen (biomarker of interest) in a specific sample, which excludes matrix effects that may interfere with the measurement of the analyte of interest.

The accuracy (% recovery) is determined by spiking a biological sample (= sample matrix: serum, plasma-EDTA, heparin, citrate) with a known amount of the purified target protein. The spiked sample is then measured in the ELISA and the concentration is calculated from the standard curve. This calculated concentration is compared to the known concentration of the protein which is expressed as a percentage of recovery. As an example, a 90% recovery means that the measured concentration in the sample is 10% lower than the actual concentration of spiked protein in the sample. It suggests that the proteins and other molecules in the sample type did not interfere with the quantification of the protein.

8. ASSAY PERFORMANCE – ASSAY VALIDATION

Evaluation of the assay´s performance characteristics is important in choosing an ELISA kit.

Select an assay that has gone through a rigorous validation process. Data on the following performance characteristics should be available:

• Accuracy (% recovery) – detection of a protein biomarker in clinical samples (acceptance criteria: ≥ 80% recovery).
• Dilution linearity and parallelism  – recovery of the analyte of interest in diluted samples (acceptance criteria: ≤ 20% difference from undiluted samples)
• Specificity & cross-reactivity – making sure that you detect only the analyte of interest
• Precision – within-run (intra-assay) precision and in-between run (inter-assay) precision – ensuring precise and reproducible results within an across assay lots (acceptance criteria: ≤ 15%). The CV (%) or coefficient of variability shows how consistent the assay is.
• Calibration – ensures consistent performance over the range of the assay of the calibration curve
• Sample stability – ensures the stability of the analyte of interest (e.g. exposure of real samples to multiple freeze-thaw cycles, stability at room temperature..).
• Sensitivity – depends on the analyte of interest.
• Dynamic range– depends on the analyte of interest.
• Specificity – verify reactivity with highly homologous proteins
• Calibration – ensures consistent performance over the range of the assay of the calibration curve
• Sample stability – ensures the stability of the analyte of interest (e.g. exposure of real samples to multiple freeze-thaw cycles, stability at room temperature..).

 

9. COMPONENTS of the KIT

Verify if the content of the ELISA assay kit includes all the necessary components e.g. controls, assay dilution buffer. Consider storage requirements such as temperature sensitivity and expiration date.

10. REFERENCES &CITATIONS

Verify for available citations of the specific ELISA kit. These publications can usually be found on the manufacturer´s website.  

11. PRODUCT ORIGIN

Check the originator of the ELISA kit – who developed and manufactured the assay?  More and more kits are repacked and are sold under different brands, although it is always the same kit.

The originator of the ELISA kit will more likely give you qualified support as they “know” their product (e.g. availability of additional calibrators, controls, buffers.., technical know-how on the kit..).

12. CUSTOMER SUPPORT

Verify if the kit provider can provide timely and helpful customer service.

 

 

 

 

Literature

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms.Gadermaier E, Tesarz M, Suciu AA, Wallwitz J, Berg G, Himmler G. J Clin Lab Anal. 2018 Feb;32(2):e22252. doi: 10.1002/jcla.22252. Epub 2017 May 11. PMID: 28493527; PMCID: PMC6816904.

 

Make Testing Easy

We at Biomedica offer tailored analytical testing services for ELISA Kits, Luminex Assays, and microRNA Analysis.

Custom Service Measurements for ELISA-Luminex-microRNA

Highlights:

-Professional: all analytics are carried out by experts

-Quality: we pursue excellence in quality

-Flexibility: tailored solutions according to your needs

-Efficient: save your time and budget – fast turnaround time

 

Learn more about the Biomedica Service Measurements  here  

Our measurement services include:

ELISA Assay Kits

We offer services for our proprietary Biomedica ELISA kits (see product list) as well as for ELISA Assays from other providers.

Luminex Technology Multiplex Assays

We utilize Luminex xMAP® (multiple analyte profiling) technology-based immunoassays, enabling the simultaneous detection and quantification of multiple biomarkers.

For more information please see our workflow chart or reach out to us directly to discuss how we can support your specific research project

NEXT-GENERATION SEQUENCING & RT-qPCR MICRORNA SERVICES

We provide a comprehensive range of high-quality RNA services, including RNA extraction, next-generation sequencing (NGS), RT-qPCR, and custom analysis of microRNA signatures, all performed by our experienced laboratory staff. Our services include:

• RNA extraction from biofluids (serum, plasma, extracellular vesicles), cells, and tissues (quality control of total RNA utilizes Bioanalyzer chips)
• Next-generation sequencing (NGS)
• RT-qPCR
• Cell-type specific microRNA/mRNA analysis in complex tissues, along with custom analysis of microRNA signatures

 

For more details about our microRNA services, please visit our website and contact us directly.

 

Literature

Circulating Micro-RNAs in Patients with Hypophosphatasia Results of the first micro-RNA analysis in HPP. Haschka J, Messner Z, Feurstein J, Hadzimuratovic B, Zwerina J, Diendorfer AB, Pultar M, Hackl M, Kuzma M, Payer J, Resch H, Kocijan R.J Clin Endocrinol Metab. 2025 Feb 11:dgaf080. doi: 10.1210/clinem/dgaf080. Epub ahead of print. PMID: 39930630.

Abstract

Biomedica’s FGF23 ELISA kits now available for the US Biotech community at 25% trial discount.

FGF23 (fibroblast growth factor 23) is a 32 kDa protein with 251 amino acids that is proteolytically processed between arginine179 and serine180 to generate N-terminal and C-terminal fragments. FGF23 is mainly secreted by osteocytes and controls phosphate and 1,25(OH)2 vitamin D homeostasis. Epidemiological data suggest that higher FGF23 concentrations are associated with all-cause mortality, cardiovascular mortality, a higher risk of myocardial infarction, stroke and heart failure.
➡️ Learn more: FGF23 – An Overview

FGF23 ELISA kits available for the US & CA

Biomedica’s FGF23 (intact) and FGF23 (C-terminal) ELISA kits

Biomedica’s FGF23 ELISA kits, widely recognized in Europe and Asia, are now also available in the US.

💡 What makes them a game-changer?

✓ MULTI-MATRIX: for plasma, serum, cell-culture
✓ CONVENIENT: 50 µl sample/well, all buffers included
✓ RELIABLE: validated following quality guidelines
✓ COMPARABLE: good correlation with existing kits
✓ EASY HANDLING: 7 prediluted standards, 2 controls
✓ TRUSTED: cited in more than 80 publications

Biomedica offers world-leading quality products at competitive pricing.

FGF23 ELISA kits available for the US & CA

🚨 Don’t miss out and order your trial kit at 25% discount. Promotion extended until June 30, 2025.

➡️ Contact our US partners or CA partner for your study quote.

Related kits: Sclerostin . OPG . Periostin . Vanin-1 . NT-proBNP . NT-proANP 

 

Literature

Non-Classical Effects of FGF23: Molecular and Clinical Features. Martínez-Heredia L, Canelo-Moreno JM, García-Fontana B, Muñoz-Torres M.Int J Mol Sci. 2024 Apr 30;25(9):4875. doi: 10.3390/ijms25094875. PMID: 38732094; PMCID: PMC11084844.

The role of fibroblast growth factor 23 in regulation of phosphate balance. Wilson R, Mukherjee-Roy N, Gattineni J. Pediatr Nephrol. 2024 Dec;39(12):3439-3451. doi: 10.1007/s00467-024-06395-5. Epub 2024 Jun 14. PMID: 38874635.

FGF23 signalling and physiology. Ho BB, Bergwitz C. J Mol Endocrinol. 2021 Feb;66(2):R23-R32. doi: 10.1530/JME-20-0178. PMID: 33338030; PMCID: PMC8782161.

The EZ4U (easy for you) colorimetric assay from Biomedica (cat. no. BI-5000) is a modified MTT assay for assessing cell metabolic activity.

Assessing metabolic activity of cells

Our EZ4U cell proliferation assay was highlighted in a recent study that investigated the development of novel chemosensitizers targeting therapy-resistant cancer stem cells (CSCs). The study offers an understanding of the structural criteria necessary for optimizing telmisartan, an angiotensin II receptor blocker, and its derivatives as non-toxic chemosensitizers. Furthermore, the findings indicate that these derivatives could be utilized to target and eliminate the cancer stem cell (CSC) population in chronic myeloid leukemia (CML), as well as the therapy-resistant CSCs in solid tumors like ovarian, prostate, lung, and breast cancers.

Learn more: Eradication of Therapy-Resistant Cancer Stem Cells by Novel Telmisartan Derivatives. Schoepf Anna M. et al., J Med Chem. 2025; 68(1):287-306.

Abstract

The present structure-activity relationship study investigates the development of novel chemosensitizers targeting therapy-resistant cancer stem cells (CSCs). We used 4′-((2-propyl-1H-benzo[d]imidazole-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid, derived from the angiotensin II type 1 receptor blocker telmisartan, as a lead structure, demonstrating that the biphenyl moiety is essential for chemosensitizing activity. Introducing a methyl carboxylate or carboxamide instead of the COOH-group significantly enhanced this effect, leading to the development of highly potent compounds. These novel, noncytotoxic chemosensitizers effectively target CSCs and overcome drug resistance by interfering with CSC persistence mechanisms─hyperactivated STAT5 signaling and increased drug transporter activity─with demonstrated efficacy in leukemia, ovarian, and prostate cancers. The carboxamide of telmisartan (telmi-amide, 7c) significantly reduced tumor growth in an imatinib-resistant leukemia xenograft model, both as monotherapy and combined with imatinib, showing promising oral bioavailability and tolerability. In summary, telmisartan derivatives act as effective chemosensitizers and offer an innovative strategy for targeting CSCs in various malignant diseases.

Determination of Metabolic Activity

Brief: ”COS-7 (2 × 10³ cells per well), IGROV-1 SP (2.5 × 10³ cells per well), A2780 V SP (1.5 × 10³ cells per well), PC3-DR (4 × 10³ cells per well), and DU145-DR (3 × 10³ cells per well) cells were seeded in 96-well plates in triplicates and after 24 h, the compounds were added at the respective concentrations. The cells were incubated at 37 °C in a humidified atmosphere (5% CO₂/95% air) for 72 h. A modified MTT colorimetric assay (EZ4U kit, Biomedica) was used to determine the metabolic activity of the tested cells, according to the manufacturer’s instructions. Absorbance was measured and the optical density of the respective FCS-containing medium and of the substrate was subtracted to exclude nonspecific staining. Metabolic activity in the absence of the compounds (CTR, DMSO) was set to 100% as reference. The results of the compounds in all assays are represented by the mean values + SEM of ≥3 independent experiments with three replicates each.”

Assessing metabolic activity of cells:

EZ4U – Cell Proliferation & Cytotoxicity Assay (cat.no. BI-5000)

-Non-radioactive & non-toxic assay

-Reliable & Sensitive

-Convenient single-step incubation  – for use on living cells

-Widely cited in more than 290 publications

 

BROCHURE – EZ4U cell proliferation and cytotoxicity assay

 

Infertility is a worldwide health issue that impacts 17.5% of couples globally (1). Although male infertility is quite prevalent, there are limited treatment options available (2).

RANKL regulates male reproductive function 

A study published by Blomberg Jensen M et al, identified RANKL as a regulator of male reproductive function: RANKL regulates male reproductive function. Nat Commun. 2021; 12(1):2450.

Abstract

Infertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Müllerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies.

In a more recent study by Andreassen CH et al , Denosumab, a RANKL inhibitor to treat osteoporosis, showed a beneficial response to treat infertile men in a subgroup of individuals: Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity. M.Cell Rep Med. 2024; 5(10):101783.

Summary

Sperm production depends on proper Sertoli-germ cell interaction, and we hypothesized that receptor activator of nuclear factor κB ligand (RANKL) activity in Sertoli cells may influence spermatogenesis. Treatment with the RANKL inhibitor denosumab, normally used to treat osteoporosis, increased testicular weight, inhibin B, and germ cell proliferation in ex vivo testis cultures and in vivo in a humanized RANKL mouse. The effect on germ cell proliferation was positively associated with baseline serum concentrations of anti-müllerian hormone (AMH). In accordance, denosumab increased germ cell proliferation in ex vivo human testis cultures with low/moderate but not severe impairment of Sertoli cell function. In a placebo-controlled randomized clinical trial, denosumab had no effect on semen quality but increased sperm concentration in a subgroup of infertile men with serum AMH ≥38 pmol/L at baseline. In conclusion, high serum AMH may increase the probability of a beneficial response to denosumab treatment in infertile men, thus suggesting a possible venue for precision medicine in male infertility.

The BIOMEDICA soluble RANKL (sRANKL) ELISA assay (cat. no. BI-20462) and Osteoprotegerin – OPG ELISA assay (cat. no. BI-20403) was utilized in both studies to quantify soluble RANKL and OPG levels in human serum and seminal fluid.

 

Key findings

• Infertile men had significant higher seminal sRANKL concentration and lower serum sRANKL levels than healthy men.
• Seminal fluid levels of sRANKL were approx. 100-fold higher than corresponding serum levels.
• High RANKL levels in seminal fluid distinguishes normal from infertile men with higher specificity than total sperm count.
• One dose of Denosumab, a RANKL inhibitor, decreases RANKL seminal fluid concentration.
• Denosumamb treatment in infertile men suggests a potential approach in addressing male infertility.

 

Soluble RANKL HS ELISA assay kit (cat. no. BI-20462)

• High sensitivity – measurable concentrations in healthy subjects
• Only ELISA that measures free, uncomplexed soluble RANKL
• Widely cited in more than 320 publications

 

OSTEOPROTEGERIN (OPG) ELISA assay kit (cat. no. BI-20403)

• Reliable – validated according to international guidelines
• Most referenced human OPG ELISA – 270 citations
• Only 20µl sample volume required 

 

Literature

1. World Health Organization. 2023. Infertility prevalence estimates 1990-2021 .
2. Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity. Andreassen CH, Holt R, Juel Mortensen L, Knudsen NK, Nielsen JE, Poulsen NN, Yahyavi SK, Boisen IM, Cui Z, Ongaro L, Hjerresen JP, Toft BG, Hasselager T, Jørgensen NR, Bernard DJ, Juul A, O’Brien C, Jørgensen A, Blomberg Jensen M.Cell Rep Med. 2024 Oct 15;5(10):101783. doi: 10.1016/j.xcrm.2024.101783. PMID: 39383870.
3. RANKL regulates male reproductive function. Blomberg Jensen M, Andreassen CH, Jørgensen A, Nielsen JE, Juel Mortensen L, Boisen IM, Schwarz P, Toppari J, Baron R, Lanske B, Juul A. Nat Commun. 2021 Apr 23;12(1):2450. doi: 10.1038/s41467-021-22734-8. PMID: 33893301; PMCID: PMC8065035.

 

Preterm birth, defined as birth before 37 weeks of gestation, affects around 10.6% of all live births globally (1). Preterm birth has been identified as a significant factor contributing to long-term cardiovascular morbidity and mortality (2). It is associated with an increased risk of elevated blood pressure, hypertension, type 1 and type 2 diabetes, decreased elasticity of the aorta, ischemic heart disease, heart failure, stroke, chronic kidney disease, and cardiovascular mortality during early childhood and young adulthood (3). A recent long-term prospective cohort study has demonstrated a connection between childhood cardiovascular risk factors and adult cardiovascular events (3).

Due to the challenge posed by prematurity and its link to cardiovascular disease, there is a need for biomarkers that can identify individuals at elevated risk, allowing for prompt therapeutic interventions. In adults, fibroblast growth factor-23 (FGF-23) has gained attention as a potential biomarker for cardiovascular disease. Elevated levels of FGF-23 are linked to hypertension, increased left ventricular mass and hypertrophy, as well as a higher incidence of coronary heart disease, heart failure, and overall cardiovascular mortality (4).

In this following pilot study a total number of 26 former very preterm infants (mean gestational age 29.5 weeks) and 21 term-born children (mean gestational age 40.3 weeks), were included. Biomarkers such as FGF23 intact (iFGF23), FGF23 (c-terminal) (cFGF23), Klotho, and HIF-1α were measured in plasma. Significantly higher concentrations were observed only for iFGF-23 and secretoneurin in former very preterm infants in comparison to term-born controls. No differences in HIF-1α, cFGF-23 and α-Klotho were detectable : Young hearts, early risks: novel cardiovascular biomarkers in former very preterm infants at kindergarten age. Mitterer W et al., Pediatr Res. 2024.

 

FGF23 can easily be measured in serum and plasma samples with a conventional ELISA assay:

BIOMEDICA – FGF-23 (intact) ELISA and FGF-23 (C-terminal) multi-matrix ELISA 

 Kit highlights

• Multi-Matrix: works with plasma, serum, and cell culture
• Convenient: 50µl sample/well, all buffers included.
• Reliable: validated quality
• Easy handling: 7 standards and 2 controls
• Comparable: strong correlation with existing methods
• Cited in over 80 publications

 

Literature

1. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, Landoulsi S, Jampathong N, Kongwattanakul K, Laopaiboon M, Lewis C, Rattanakanokchai S, Teng DN, Thinkhamrop J, Watananirun K, Zhang J, Zhou W, Gülmezoglu AM. Lancet Glob Health. 2019 Jan;7(1):e37-e46. doi: 10.1016/S2214-109X(18)30451-0. Epub 2018 Oct 30. PMID: 30389451; PMCID: PMC6293055.
2. Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations. Risnes K, Bilsteen JF, Brown P, Pulakka A, Andersen AN, Opdahl S, Kajantie E, Sandin S.JAMA Netw Open. 2021 Jan 4;4(1):e2032779. doi: 10.1001/jamanetworkopen.2020.32779. Erratum in: JAMA Netw Open. 2021 Feb 1;4(2):e210068. doi: 10.1001/jamanetworkopen.2021.0068. PMID: 33416885; PMCID: PMC7794670.
3. Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events. Jacobs DR Jr, Woo JG, Sinaiko AR, Daniels SR, Ikonen J, Juonala M, Kartiosuo N, Lehtimäki T, Magnussen CG, Viikari JSA, Zhang N, Bazzano LA, Burns TL, Prineas RJ, Steinberger J, Urbina EM, Venn AJ, Raitakari OT, Dwyer T.N Engl J Med. 2022 May 19;386(20):1877-1888. doi: 10.1056/NEJMoa2109191. Epub 2022 Apr 4. PMID: 35373933; PMCID: PMC9563825.
4. Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the Atherosclerosis Risk in Communities study. Lutsey PL, Alonso A, Selvin E, Pankow JS, Michos ED, Agarwal SK, Loehr LR, Eckfeldt JH, Coresh J J Am Heart Assoc. 2014 Jun 10;3(3):e000936. doi: 10.1161/JAHA.114.000936. PMID: 24922628; PMCID: PMC4309096.

 

 

Our Osteoprotegerin (OPG) ELISA assay was highlighted in a recent study assessing serum OPG levels during acute inflammatory states induced by a bacterial or viral infection in children. The researchers investigated whether OPG increases during acute inflammatory states and if its levels correlate with other biomarkers. OSTEOPROTEGERIN increases in infection-induced acute inflammation

OPG, a key regulator of bone metabolism (1). OPG suppresses osteoclastogenesis and is expressed in peripheral lymph nodes, osteoblasts, and bone marrow stromal cells. Moreover, OPG is involved in the inflammatory processes of chronic conditions, such as rheumatoid arthritis, ankylosing spondylitis, and Crohn’s disease. The elevated serum levels of OPG observed in these conditions are likely due to the activation of pro-inflammatory proteins like tumor necrosis factor α (TNF-α), which enhances OPG expression (3, 4).

OSTEOPROTEGERIN serum levels increase in infection-induced acute inflammation

Discoveries in recent years have revealed a close relationship between bone biology and immunity. This connection is emphasized by shared regulatory molecules, including cytokines, receptors, and transcription factors. In particular, the receptor activator of nuclear factor NF-kB (RANK) and its ligand (RANKL) are crucial for osteoclast differentiation and the development of immune organs such as the bone marrow, thymus, lymph nodes, and gut-associated lymphoid tissue. The third key element in this system is osteoprotegerin (OPG), a decoy receptor that inhibits RANK signaling by binding to RANKL (2).

Osteoprotegerin (OPG) can reliably be measured with a conventional ELISA assay

 Biomedica OPG ELISA (cat. no. BI-20403)

• Method: Sandwich ELISA, 12×8-well detachable strips
• Sample: Serum, plasma (EDTA, citrate, heparin)
• Sample volume: 20μl / well
• Detection range: 1.25-20 pmol/L (= 25 – 400 pg/mL)
• Sensitivity: 0.07 pmol/L (= 1.4 pg/mL)
• Incubation time: 4 h + 1 h + 30 min (room temperature)
• Precision: In-between-run (n=12): ≤ 5 % CV: Within-run (n=5): ≤ 3 % CV
• Widely cited in over 260 publications!

 

Fully validated Osteoprotegerin ELISA assay – validation data can be found here .

Osteoprotegerin in infection-induced acute inflammatory states in children. Giannakopoulos A et al., 2024.  

Key findings:

-The study provides the proof of concept for an increase of OPG during acute inflammatory states induced only by bacterial infections.

-OPG returns to baseline after resolution of the infection.

-OPG correlates well with CRP only in the group with bacterial infection, although with a lower sensitivity than CRP.

 

Literature

1. Osteoprotegerin in infection-induced acute inflammatory states in children. Giannakopoulos A, Efthymiadou A, Kritikou D, Chrysis D. Heliyon. 2024 Mar 7;10(6):e27565. doi: 10.1016/j.heliyon.2024.e27565. PMID: 38509997; PMCID: PMC10951505.
2. Discovery of the RANKL/RANK/OPG system. Yasuda H. J Bone Miner Metab. 2021 Jan;39(1):2-11. doi: 10.1007/s00774-020-01175-1. Epub 2021 Jan 3. Erratum in: J Bone Miner Metab. 2021 Jan;39(1):12. doi: 10.1007/s00774-021-01203-8. PMID: 33389131.
3. The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer. De Leon-Oliva D, Barrena-Blázquez S, Jiménez-Álvarez L, Fraile-Martinez O, García-Montero C, López-González L, Torres-Carranza D, García-Puente LM, Carranza ST, Álvarez-Mon MÁ, Álvarez-Mon M, Diaz R, Ortega MA. Medicina (Kaunas). 2023 Sep 30;59(10):1752. doi: 10.3390/medicina59101752. PMID: 37893470; PMCID: PMC10608105.
4. Interaction between bone and immune cells: Implications for postmenopausal osteoporosis. Fischer V, Haffner-Luntzer M. Semin Cell Dev Biol. 2022 Mar;123:14-21. doi: 10.1016/j.semcdb.2021.05.014. Epub 2021 May 20. PMID: 34024716.

The Biomedica SCLEROSTIN ELISA Assay Kit (cat. no. BI-20492) was utilized in a recent publication identifying high-risk frailty groups (full publication).  

Sclerostin (SOST) ELISA  (cat. no. BI-20492)

• Most referenced Sclerostin ELISA in over 300 citations
• Low sample volume – 20µl / well
• Validation following international guidelines

 

SCLEROSTIN – a biomarker for predicting the onset of frailty

SCLEROSTIN, a protein that is predominantly produced by osteocytes, has gained considerable attention for its role in inhibiting bone formation (1).  In addition to its effects on bone, sclerostin has been shown to have hormonal functions in non-skeletal tissues like adipocytes, blood vessels, muscles, and kidneys, where it plays a role in endothelial function, energy balance, glucose metabolism, physical performance, and kidney health (2-4). This broader systemic involvement highlights its potential effects on overall health.

Sclerostin circulates in the blood as a secreted protein and can easily be measured by ELISA assay technology, making it a promising biomarker for various age-related conditions, such as osteoporosis, sarcopenia, and cardiovascular diseases. The link between serum Sclerostin levels and frailty has not yet been studied. In a recent clinical study the relationship between circulating sclerostin levels and frailty, using both the phenotypic frailty model and the frailty index in a group of older adults has been investigated.

SCLEROSTIN – a biomarker for predicting the onset of frailty

Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health. Baek JY et al., Endocrinol Metab (Seoul). 2025; 40(1):73-81. doi: 10.3803/EnM.2024.2100. PMCID: PMC11898323.

“Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.

Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).

Conclusion: These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.”

 

Literature

1. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F, Giusti F, Palmini G, Brandi ML.Osteoporos Int. 2023 Feb;34(2):213-238. doi: 10.1007/s00198-022-06523-7. Epub 2022 Aug 18. PMID: 35982318.
2. Sclerostin: From Molecule to Clinical Biomarker. Omran A, Atanasova D, Landgren F, Magnusson P. Int J Mol Sci. 2022 Apr 26;23(9):4751. doi: 10.3390/ijms23094751. PMID: 35563144; PMCID: PMC9104784.
3. Role of Sclerostin in Cardiovascular Disease. Golledge J, Thanigaimani S. Arterioscler Thromb Vasc Biol. 2022 Jul;42(7):e187-e202. doi: 10.1161/ATVBAHA.122.317635. Epub 2022 May 12. PMID: 35546488.
4. Exploring the Role of Sclerostin as a Biomarker of Cardiovascular Disease and Mortality: A Scoping Review. Sanabria-de la Torre R, González-Salvatierra S, García-Fontana C, Andújar-Vera F, García-Fontana B, Muñoz-Torres M, Riquelme-Gallego B. Int J Environ Res Public Health. 2022 Nov 30;19(23):15981. doi: 10.3390/ijerph192315981. PMID: 36498053; PMCID: PMC9739125.

Our Fibroblast Growth Factor-23 (FGF-23) C-terminal ELISA assay was highlighted in a recent clinical study in hypertensive patients. The researchers evaluated whether individuals with “functional vitamin D deficiency” significantly benefit from vitamin D supplementation. As of now, there is no widely accepted definition of functional vitamin D deficiency. Thus, the authors explored the hypothesis that a specific definition of functional vitamin D deficiency could help identify individuals who would significantly benefit from vitamin D supplementation.

The authors concluded that the criteria for functional vitamin D deficiency indicate that patients with vitamin D deficiency do not experience significant improvements in bone markers or cardiovascular risk factors following vitamin D supplementation. Furthermore, additional research is needed to determine whether measuring vitamin D metabolites alongside 25(OH)D is beneficial for accurately classifying vitamin D status and identifying individuals who would particularly benefit from vitamin D treatment.

Classification of Vitamin D status based on its metabolism

Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients. Zelzer S, Meinitzer A, Enko D, Keppel MH, Herrmann M, Theiler-Schwetz V, Trummer C, Schmitt L, Tomaschitz A, Sadoghi P, Dierkes J, Pludowski P, Zittermann A, März W, Pilz S. Nutrients. 2024 Mar 14;16(6):839. doi: 10.3390/nu16060839. PMID: 38542750; PMCID: PMC10975656.

Abstract

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of “functional vitamin D deficiency”, i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

BIOMEDICA provides two distinct ELISA assays to reliably quantify FGF23 concentrations in human serum and plasma.

 FGF23 intact ELISA (cat. no. BI-20700)

 FGF23 (C-terminal) ELISA (cat. no. BI-20702)

Features and benefits  

• MULTI-MATRIX: for plasma, serum, cell-culture

• CONVENIENT: 50 µl sample/well, all buffers included

• RELIABLE: validated following quality guidelines

• COMPARABLE: good correlation with existing kits

• EASY HANDLING: 7 prediluted standards, 2 controls

• TRUSTED: cited in more than 80 publications

All Assays are Developed & Manufactured by Biomedica

Biomarkers have long been used as indicators of biological changes. In the context of drug development, they serve two key functions: predicting drug efficacy and detecting potential toxicity.

Cardiotoxicity is a significant reason for the failure of preclinical safety tests during the drug development process. Consequently, monitoring cardiac toxicity through biomarkers is a crucial component of drug development.

Cardiac Safety Biomarkers for Toxicity Testing

The biomarkers NT-proANP and NT-proBNP are cardiac hormones released when the heart muscle is stretched. They are part of the natriuretic peptides family and serve as cardiac biomarkers in both human studies and in animal studies (1-4).

In preclinical settings, they have been effectively utilized to identify cardiotoxicity (3). NT-proBNP and NT-proANP have proven to be valuable tools that enhance the early detection of cardiovascular injury during drug development (4). NT-proANP has also been measured to study Heart Failure with preserved Ejection Fraction (HFpEF) in a mouse model to probe preload-dependency (5). Furthermore, N-terminal pro-atrial natriuretic peptide (NT-proANP) was also quantified to assess left ventricular (LV) function in a rat model of cardiac arrest (CA) (6).

Biomedica provides reliable ELISA kits for the quantification of NT-proBNP and NT-proANP in samples from humans and rodents.

Rat NT-proBNP ELISA (cat. no. BI-1204R)

• Sample type: rat serum, plasma
• Sample volume: 10 µL/well
• Sensitivity: LOD 21 pg/ml
• Standard curve range: 0 – 3200 pg/ml (0 / 100 / 200 / 400 / 800 / 1600 / 3200 pg/ml)
• Assay time: 3.5 hours
• Protocol booklet click here – reference values provided

 

NT-proBNP ELISA (cat.no. SK-1204) – for human serum and plasma samples

• CE marked for IVD use in the EU
• Proficiency testing , saliva protocol
• Widely cited

 

NT-proANP ELISA (Cat. No. BI-20892)

Due to the high sequence homology of NT-proANP among species the assay has also been used in rodent (rat, mouse) rabbit, and dog samples.

• Sample types: Serum, plasma, urine, cell culture supernatant (human, rat, mouse, rabbit samples)
• Sample volume: 10 µL/well
• Sensitivity: LOD 0.05 nmol/l (= 0.64 ng/ml)
• Standard curve range: 0 – 10 nmol/l (= 0 – 127 ng/ml)
• Assay time: 3.5 hours
• Citations all , citations with use of rat/mouse samples
• Protocol Booklet click here

 

Literature

1. Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study. Schirmer H and Omland T. Eur Heart J. 1999; 20(10):755-63. doi: 10.1053/euhj.1998.1396. Erratum in: Eur Heart J 1999 Oct;20(19):1439. PMID: 10329067.
2.  Biomarkers for the diagnosis and management of heart failure. Castiglione V et al., Heart Fail Rev. 2022; 27(2):625-643. PMID: 33852110.
3.  Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME et al., Toxicol Pathol. 2017; 45(2):344-352. PMID: 27102652.
4.  Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. Stokes AH et al., Int J Toxicol. 2015; 34(2):151-61. PMID: 25722321.
5. Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF). Jacobsen JCBet al., Acta Physiol (Oxf). 2024; 240(3):e14099. PMID: 38230889.
6. Post-cardiac arrest temporal evolution of left ventricular function in a rat model: speckle-tracking echocardiography and cardiac circulating biomarkers. De Giorgio Det al., Eur Heart J Imaging Methods Pract. 2024; 2(1):qyae006. doi: 10.1093/ehjimp/qyae006. PMID: 39045191.