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• Omega-6 Fatty Acids and Biomarkers of Inflammation

Chronic inflammation is linked to various health disorders (1). Omega-6 polyunsaturated fatty acids (n-6 PUFAs), especially linoleic and arachidonic acid, have both pro- and anti-inflammatory effects, resulting in conflicting opinions on whether their consumption should be reduced (1, 2).

Omega-6 Fatty Acids and Biomarkers of Inflammation

In a recent study researchers explored whether red blood cell omega-6 polyunsaturated fatty acids (RBC n-6 PUFAs) are pro-inflammatory by examining their association with various inflammation biomarkers (4).

Red Blood Cell Omega-6 Fatty Acids and Biomarkers of Inflammation in the Framingham Offspring Study. Lai HTM et al., Nutrients. 2025.  

Abstract

Background/objectives: Chronic inflammation is recognized as an important risk factor for a variety of health disorders. Omega-6 polyunsaturated fatty acids (n-6 PUFAs), particularly linoleic (LA) and arachidonic acid (AA), have been shown to be either pro- or anti-inflammatory, and researchers have advocated both for and against reducing their dietary intake. This study sought to correlate the levels of ten inflammation-related biomarkers across multiple pathways with red blood cell (RBC) membrane levels of the major dietary and circulating n-6 PUFAs.

Methods: We included 2777 participants (mean age: 66 ± 9 years, 54% women, 9.8% minorities) from the Framingham Offspring and minority-enriched Omni cohorts, and calculated partial correlation coefficients.

Results: After multivariable adjustment, RBC LA was inversely correlated (all p ≤ 0.05) with five markers of inflammation, receptors, or pathways: C-reactive protein (r = -0.06); soluble interleukin-6 (r = -0.15); intercellular adhesion molecule-1 (r = -0.09); monocyte chemoattractant protein-1 (r = -0.07); and P-selectin (r = -0.07). RBC AA was inversely correlated (all p ≤ 0.05) with soluble interleukin-6 (r = -0.10); intercellular adhesion molecule-1 (r = -0.14); monocyte chemoattractant protein-1, and (r = -0.06); and osteoprotegerin (r = -0.07). Lipoprotein-associated phospholipase-A2 mass and activity, urinary isoprostanes, and tumor necrosis factor receptor-2 were not significantly correlated with LA or AA.

Conclusions: In our large community-based study, we observed weak but statistically significant inverse associations between several types of inflammatory biomarkers with RBC n-6 PUFAs. Our findings do not support the hypothesis that omega-6 fatty acids are pro-inflammatory.

 

The Biomedica Osteoprotegerin (OPG) ELISA assay was utilized in the above study.

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

• RELIABLE – full validation protocol (spike recovery, dilution linearity. )
• EFFICIENT: only 20 µl sample / well (protocol booklet)
• TRUSTED – most referenced OPG ELISA, cited in over 270 publications

 

 

OPG ELISA Assay Principle:

 

Literature

1. Inflammation: The Cause of All Diseases. Chavda VP, Feehan J, Apostolopoulos V. 2024 Nov 18;13(22):1906. doi: 10.3390/cells13221906. PMID: 39594654; PMCID: PMC11592557.
2. Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells. Rutting S, Xenaki D, Lau E, Horvat J, Wood LG, Hansbro PM, Oliver BG. Am J Physiol Lung Cell Mol Physiol. 2018 Jun 1;314(6):L922-L935. doi: 10.1152/ajplung.00438.2017. Epub 2018 Jan 25. PMID: 29368548.
3. Omega-6 fatty acids and inflammation. Innes JK, Calder PC. Prostaglandins Leukot Essent Fatty Acids. 2018 May;132:41-48. doi: 10.1016/j.plefa.2018.03.004. Epub 2018 Mar 22. PMID: 29610056.
4. Red Blood Cell Omega-6 Fatty Acids and Biomarkers of Inflammation in the Framingham Offspring Study. Lai HTM, Ryder NA, Tintle NL, Jackson KH, Kris-Etherton PM, Harris WS. Nutrients. 2025 Jun 22;17(13):2076. doi: 10.3390/nu17132076. PMID: 40647182; PMCID: PMC12251348.

microbial–metabolic signatures associated with plaque destabilization and resolution

Coronary artery disease (CAD) is the primary cause of death worldwide (1). Clinical manifestations of CAD are divided into chronic or stable CAD (sCAD), characterized by gradual artery narrowing, and acute coronary syndromes (ACS), which involve a sudden interruption of blood flow (2).

The human gut hosts trillions of microbes, known as the gut microbiota, which play key roles in metabolism and immune regulation. Its composition, influenced by environment and genetics, and changes in the gut microbiota have been linked to CAD development. Microbial metabolites can also enter circulation and contribute to CAD pathology (3).

Gut-Heart Axis in Coronary Artery Disease

In a recent study researchers explored the role of the gut-heart axis in coronary artery disease: Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery.  Xu J et al., Imeta. 2025.

Key highlights:

• Changes in the gut microbiome are closely linked to CAD progression.
• Changes are observed across normal coronary arteries, stable CAD, and acute coronary syndrome (ACS).
• Multi-omics machine learning models effectively differentiated CAD subtypes, outperforming traditional clinical risk factors.

 

Our human NT-proBNP assay was featured in this study.

NT-proBNP ELISA (cat. no. SK-1204)

√  CONVENIENT – can be used in every lab

√  RELIABLE – Full validation package

√  EASY – 5 pre-diluted standards and 2 controls included

√  TRUSTED – Widely cited in more than 140 publications 

 

Literature

1. Global prevalence of coronary artery disease: an update from the global burden of disease study. Stark, B, Johnson, C, Roth, G. JACC.2024 Apr, 83 (13_Supplement) 2320.
2. Acute and chronic coronary artery disease. Lancellotti P. Acta Cardiol. 2024 Apr;79(2):105-108. PMID: 38628088.
3. The role of gut microbiota in cardiovascular diseases and their potential as novel therapeutic targets. Yamashita T. J Cardiol. 2025 Aug;86(2):141-147. doi: 10.1016/j.jjcc.2025.05.002. Epub 2025 May 21. PMID: 40409712.
4. Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery. Xu J et al., Imeta. 2025 Sep 19;4(5):e70079. PMID: 41112052.

Insights from animal models and MSC transplantation

Pulmonary Veno-Occlusive Disease (PVOD), also known as “pulmonary arterial hypertension (PAH), is a rare form of pulmonary hypertension. It is caused by progressive blockage of small veins in the lungs leading to increased pressure followed by right-sided heart failure (1). As effective treatments are limited, lung transplantation remains the only available option. There is no effective medical treatment and lung transplantation is the only curative option. The prognosis is unfavorable, with an average life expectancy of two years following onset of symptoms (2).

Developing PVOD-Specific Therapies

In a recent study researchers investigated the impact of allogeneic mesenchymal stem cell (ASCs) transplantation on lung tissue and its potential in reducing pulmonary hypertension in a rat model of PVOD. Additionally, they assessed whether this intervention contributes to the improvement of right ventricular hypertrophy (3). Continued and future research involving animal models alongside patient samples offers hope for developing PVOD-specific therapies that can prevent and/or treat the disease (4).

Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model.

Abstract

Background: Pulmonary veno-occlusive disease (PVOD) is a rare subtype of disease that causes pulmonary hypertension with vascular involvement of postcapillary structures of pulmonary vasculature. The disease has a poor prognosis with no effective therapy. The study aimed to determine whether adipose-derived mesenchymal stem cells (ASCs) alleviate pulmonary hypertension and right ventricular hypertrophy in a rat model of PVOD.

Methods: Allogeneic ASCs were intravenously administered to a rat model of PVOD induced by mitomycin C. Then, muscularization in pulmonary microvessels, right ventricular systolic pressure (RVSP), and right ventricular hypertrophy were assessed using immunohistochemistry, right heart catheterization, heart weight, and hematoxylin–eosin (HE) staining. Body weight over time and survival rates were assessed.

Results: ASC transplantation substantially contributed to the reduction of pulmonary microvascular muscularization in the PVOD rat model but not to the decrease in RVSP. Furthermore, it led to the attenuation of right ventricular hypertrophy and a considerable decrease in wall thickness. However, repeated ASC administration increased the mortality rate in the PVOD rat models.

Conclusions: To the best of our knowledge, this is the first study to analyze the effects of ASC transplantation in a rat model of PVOD. While intravenous ASC transplantation exerts beneficial effects on the lungs and right ventricle, adverse events may occur depending on the administration method. Therefore, intravenous ASC transplantation should be performed with caution.

 

NT-proBNP measurements were successfully performed in the PVOD rat model in rat serum utilizing our Rat NT-proBNP ELISA assay.

Rat NT-pro BNP ELISA assay (cat. no. BI-1204R)

• Efficient – only 10 µl / well sample
• Accurate – kit control included – protocol booklet click here
• Reliable – sample values provided –  validation data click here
• Trusted – cited using various rat models – citations click here 

Read our first independant review

Rat NT-proBNP ELISA assay

 

Related products:

NT-proANP ELISA Assay (cat. no. BI-20892)

• Small sample volume – 10 µl / well
• Assay suitable for rat and mouse samples – NT-proANP as a cardiovascular safety biomarker in rats Citations

 

Literature:

1. Diagnosis and management of pulmonary veno-occlusive disease. Solinas S, Boucly A, Beurnier A, Kularatne M, Grynblat J, Eyries M, Dorfmüller P, Sitbon O, Humbert M, Montani D. Expert Rev Respir Med. 2023 Jul-Dec;17(8):635-649. doi: 10.1080/17476348.2023.2247989. Epub 2023 Aug 21. PMID: 37578057.
2. Pulmonary Veno-Occlusive Disease. Siddiqui NA, Charoenpong P. 2023 Jul 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 36256776.
3. Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model. Katagiri J, Homma J, Takagi R, Sekine H, Shinkawa T, Niinami H, Shimizu T.Stem Cell Res Ther. 2025 May 28;16(1):258. doi: 10.1186/s13287-025-04400-8. PMID: 40437633; PMCID: PMC12121274.
4. Pulmonary veno-occlusive disease: Insights from animal models. Hata A, Gur B, Kalra J, Prabhakar A. Vascul Pharmacol. 2025 Sep 10;161:107547. doi: 10.1016/j.vph.2025.107547. Epub ahead of print. PMID: 40939813.

Sclerostin is a glycoprotein primarily produced by osteocytes, bone cells embedded within the bone matrix. It plays a crucial role in regulating bone metabolism by acting as Wnt signaling pathway antagonist, essential for promoting bone formation. By inhibiting this pathway, sclerostin effectively reduces osteoblast activity and bone formation, thereby maintaining a balance between bone growth and resorption (1).

Standardizing Sclerostin Measurement

Sclerostin has emerged as a promising therapeutic target for bone-related disorders, particularly osteoporosis. By inhibiting sclerostin, it is possible to enhance Wnt signaling, thereby stimulating osteoblast activity and promoting new bone formation. This approach aims to counteract the excessive bone loss characteristic of osteoporosis and other metabolic bone diseases. Several sclerostin inhibitors have been developed, with romosozumab being the most notable. Romosozumab is a monoclonal antibody that binds to sclerostin, effectively neutralizing its activity (2, 3).

Sclerostin and Type 2 Diabetes Mellitus

Epidemiological studies have reported that Type 2 diabetes (T2D) is linked to a higher risk of fractures (4). In addition, Sclerostin has been shown to be associated with fasting insulin levels and homoeostatic model assessment-insulin resistance (HOMA-IR) (5). Numerous studies have demonstrated increased circulating Sclerostin levels in T2D patients (6, 7). Furthermore, serum sclerostin levels also correlate with the duration of T2DM, glycated hemoglobin, bone turnover markers, and BMD in T2DM patients (6). Elevated Sclerostin levels have been linked to a higher risk of vertebral fractures in T2DM patients, regardless of BMD and bone turnover, indicating that sclerostin may reflect bone fragility related to deteriorated bone quality within gender-specific BMD T-score ranges (8).

A recent study by Traechslin C et al. (7), investigated the association of total and bioactive serum Sclerostin levels with bone metabolism in type 2 diabetes mellitus (T2DM) using three different Sclerostin ELISA assays.

Key highlights:

• Identifying diabetes patients at risk for fragility fractures is challenging.
• Sclerostin levels are significantly increased in T2DM, particularly in men when bioactive Sclerostin is measured.
• Significant positive correlation between serum Sclerostin and Bone Mineral Density-Sclerostin could be a useful marker in evaluating bone fragility in T2DM patients.
• Bioactive sclerostin more accurately reflects bone metabolism based on clinical findings.

 

These findings are an initial step to standardize sclerostin measurement to evaluate bone metabolism.

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• TRUSTED – validated for clinical samples  (validation data file)
• LOW sample volume – 20µl sample /well (protocol booklet)

 

Bioactive SCLEROSTIN ELISA – Binding Sites of antibodies utilized in the assay

 

 

Sclerostin ELISA (cat. no. BI-20492)

• TRUSTED – most referenced
• LOW sample volume – 20µl sample /well (protocol booklet)
• RELIABLE – validated  following international quality guidelines

 

 

 

Association of total and bioactive serum sclerostin levels with bone metabolism in type 2 diabetes mellitus. Traechslin C et al, Clin Transl Endocrinol; 2025.

Abstract

Background: Sclerostin has been associated with decreased bone turnover in patients with type 2 diabetes mellitus (T2DM). The relationship with bone turnover markers (BTMs) and bone mineral density (BMD) remains unclear. We investigate the relationship between total and bioactive sclerostin measured by three different assays with BTMs and BMD in patients with T2DM compared to healthy controls.

Methods: Baseline data from the cross-sectional multicenter DiabOS-study in Switzerland were analysed. Total and bioactive serum sclerostin levels were measured using three different ELISA-based sclerostin assays (Sclerostin Biomedica, Sclerostin bioactive Biomedica and Sclerostin hsTECO). Sclerostin levels in patients with T2DM and controls were correlated with BTMs and BMD.

Results: Data were analysed from 78 men and postmenopausal women with T2DM and 37 controls (aged 50-75 years). Serum sclerostin levels, adjusted for estimated glomerular filtration rate (eGFR), were higher in patients with T2DM compared to controls with all three assays. In a gender subgroup analysis, bioactive sclerostin levels remained significantly elevated in men with T2DM (T2DM, 106.8 ± 39.9 pmol/L; controls, 88.3 ± 21.3 pmol/L, p = 0.03).Univariate analysis showed consistent significant correlations with all sclerostin assays for age, eGFR, glycated hemoglobin A1c and diabetes duration. However, in multivariate analysis, eGFR remained the only significant determinant of serum sclerostin levels. Sclerostin levels in patients with T2DM showed significant positive correlations with BMD but no significant correlations with BTMs.

Conclusions: We demonstrate a significant positive association of bioactive serum sclerostin with BMD at all measured sites in patients with T2DM, which may support its utility in the assessment of bone fragility in this population.

Literature

1. 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.
2. A practical approach for anabolic treatment of bone fragility with romosozumab. Cianferotti L, Cipriani C, Palermo A, Viapiana O, Zavatta G, Mazziotti G.J Endocrinol Invest. 2024 Nov;47(11):2649-2662. doi: 10.1007/s40618-024-02395-2. Epub 2024 May 24. PMID: 38789679.
3. Romosozumab. Krupa KN, Parmar M, Delo LF. 2024 Jul 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 36256789.
4. Skeletal Fragility in Type 2 Diabetes Mellitus. Starup-Linde J, Hygum K, Langdahl BL.Endocrinol Metab (Seoul). 2018 Sep;33(3):339-351. doi: 10.3803/EnM.2018.33.3.339. PMID: 30229573; PMCID: PMC6145952.
5. The association between sclerostin and incident type 2 diabetes risk: a cohort study. Yu OH, Richards B, Berger C, Josse RG, Leslie WD, Goltzman D, Kaiser SM, Kovacs CS, Davison KS. Clin Endocrinol (Oxf). 2017 Apr;86(4):520-525. doi: 10.1111/cen.13300. Epub 2017 Jan 26. PMID: 28090669.
6. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. García-Martín A, Rozas-Moreno P, Reyes-García R, Morales-Santana S, García-Fontana B, García-Salcedo JA, Muñoz-Torres M. J Clin Endocrinol Metab. 2012 Jan;97(1):234-41. doi: 10.1210/jc.2011-2186. Epub 2011 Oct 26. PMID: 22031520.
7. Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, Capodarca C, Franci MB, Campagna MS, Calabrò A, Cataldo D, Stolakis K, Dotta F, Nuti R. J Clin Endocrinol Metab. 2012 May;97(5):1737-44. doi: 10.1210/jc.2011-2958. Epub 2012 Mar 7. PMID: 22399511.
8. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. Yamamoto M, Yamauchi M, Sugimoto T. J Clin Endocrinol Metab. 2013 Oct;98(10):4030-7. doi: 10.1210/jc.2013-2143. Epub 2013 Jul 26. PMID: 23894157.
9. Association of total and bioactive serum sclerostin levels with bone metabolism in type 2 diabetes mellitus. Traechslin C, Sewing L, Baumann S, Grize L, Vavanikunnel J, Kraenzlin M, Henzen C, Meier C.J Clin Transl Endocrinol. 2025 Apr 8;40:100393. doi: 10.1016/j.jcte.2025.100393. PMID: 40275939; PMCID: PMC12019839.

 

 

 

About Dickkopf-1 (DKK-1)  – a  key regulator of the Wnt signaling pathway

DKK-1 is a protein that functions as a key regulator of the Wnt signaling pathway, which is essential for various cellular processes including growth, development, and tissue homeostasis. DKK-1 primarily acts as an antagonist of the Wnt pathway by binding to specific receptors, thereby inhibiting Wnt signaling activity.

The Wnt pathway is a complex and highly conserved signaling cascade that plays a crucial role in regulating cell growth, differentiation, migration, and tissue development. It also plays a critical role in bone biology, particularly in the regulation of bone formation and remodeling as it influences the activity of osteoblasts, the cells responsible for building new bone, and helps maintain bone mass and strength.

DKK-1 linked to poor prognosis and metastasis in breast cancer

DKK-1 a potential biomarker for disease progression in breast cancer

DKK-1 plays a crucial role in breast cancer by modulating the Wnt signaling pathway, which regulates cell proliferation, differentiation, and migration. Abnormal expression of DKK-1 has been detected in breast cancer, with elevated levels often associated with tumor progression and metastasis, especially to the bones. Increased DKK-1 expression has been linked to poorer prognosis and a higher risk of bone metastases, as it affects the tumor microenvironment and bone remodeling processes (1-3). Therefore, DKK-1 is regarded as a potential biomarker for disease progression and a promising target for therapeutic strategies in breast cancer treatment (4, 5).

DKK-1 suppresses NK cell cytotoxicity in breast cancer

Breast cancer patients with progressive bone metastases exhibit higher levels of DKK-1 and a decreased number of cytotoxic NK cells compared to those with stable disease. Recent findings suggest that DKK1 promotes a tumor-supporting environment by suppressing NK cell activity in breast cancer (6).

Breast cancer is minimally immunogenic, which allows it to evade T cell recognition and results in limited responsiveness to immune checkpoint blockade. Additionally, breast cancer cells can evade NK cell-mediated immune surveillance. Recent findings suggest that DKK-1 promotes a tumor-supporting environment in breast cancer by suppressing NK cell function (7).

Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer .  Lee S et al., 2025; Nat Commun.

Abstract

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone. By using genetic approaches, we find that bone-derived DKK1 contributes to the systemic DKK1 elevation in tumor-bearing female mice, while CAFs contribute to DKK1 at primary tumor site. Systemic and bone-specific DKK1 targeting reduce tumor growth. Intriguingly, deletion of CAF-derived DKK1 also limits breast cancer progression, without affecting its levels in circulation, and regardless of DKK1 expression in the tumor cells. While not directly supporting tumor proliferation, stromal-DKK1 suppresses NK cell activation and cytotoxicity by downregulating AKT/ERK/S6 phosphorylation. Importantly, increased DKK1 levels and reduced cytotoxic NK cells are detected in women with progressive breast cancer. Our findings indicate that DKK1 represents a barrier to anti-tumor immunity through suppression of NK cells.

DKK-1 can reliably be measured in biological fluids with a conventional ELISA assay.

DKK-1 ELISA Assay Highlights (Cat. No. BI-20413)

• Small sample volume – 10 µl / well
• Direct measurement- no pre-dilution of samples required!
• Reliable – full validation package
• Easy – 6 standards and control included
• Trusted – widely cited in more than 180 publications
• Protocol booklet link

 

Download our DKK-1 Leaflet here

 

 

 

Literature

1. Increased Dickkopf-1 expression in breast cancer bone metastases. Voorzanger-Rousselot N, Goehrig D, Journe F, Doriath V, Body JJ, Clézardin P, Garnero P. Br J Cancer. 2007 Oct 8;97(7):964-70. doi: 10.1038/sj.bjc.6603959. Epub 2007 Sep 18. PMID: 17876334; PMCID: PMC2360424.
2. Serum Dickkopf-1 acts as a new biomarker in human breast cancer. Liu JT, Guo WB, Sun JY. Minerva Med. 2017 Aug;108(4):334-340. doi: 10.23736/S0026-4806.17.04807-8. Epub 2017 Mar 1. PMID: 28248066.
3. Dickkopf-1: A Promising Target for Cancer Immunotherapy. Chu HY, Chen Z, Wang L, Zhang ZK, Tan X, Liu S, Zhang BT, Lu A, Yu Y, Zhang G. Front Immunol. 2021 May 20;12:658097. doi: 10.3389/fimmu.2021.658097. PMID: 34093545; PMCID: PMC8174842.
4. Dickkopf-1 as a mediator and novel target in malignant bone disease. Rachner TD, Göbel A, Benad-Mehner P, Hofbauer LC, Rauner M. Cancer Lett. 2014 May 1;346(2):172-7. doi: 10.1016/j.canlet.2014.01.010. Epub 2014 Jan 22. PMID: 24462802.
5. Dkk1 as a Prognostic Marker for Neoadjuvant Chemotherapy Response in Breast Cancer Patients. Kasoha M, Steinbach AK, Bohle RM, Linxweiler B, Haj Hamoud B, Doerk M, Nigdelis MP, Stotz L, Zimmermann JSM, Solomayer EF, Kaya AC, Radosa JC. Cancers (Basel). 2024 Jan 18;16(2):419. doi: 10.3390/cancers16020419. PMID: 38254908; PMCID: PMC10814026.
6. Cancer-associated fibroblast-derived Dickkopf-1 suppresses NK cell cytotoxicity in breast cancer. Faccio R, Lee S, Ricci B, Tran J, Ye J, Clever D, Eul E, Wang J, Wong P, Ma C, Fehniger T. Res Sq [Preprint]. 2024 Apr 8:rs.3.rs-4202878. doi: 10.21203/rs.3.rs-4202878/v1. Update in: Nat Commun. 2025 Jan 30;16(1):1183. doi: 10.1038/s41467-025-56420-w. PMID: 38659818; PMCID: PMC11042392.
7. Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer. Lee S, Ricci B, Tran J, Eul E, Ye J, Ren Q, Clever D, Wang J, Wong P, Haas MS, Stewart SA, Ma CX, Fehniger TA, Faccio R. Nat Commun. 2025 Jan 30;16(1):1183. doi: 10.1038/s41467-025-56420-w. PMID: 39885132; PMCID: PMC11782527.

 

During Breast Cancer Awareness Month, let´s share insights on emerging biomarkers such as PERIOSTIN that offer potential for improved diagnosis, prognosis, and personalized therapy.

PERIOSTIN is a potential marker for breast cancer progression

 Periostin is a matricellular protein that plays a significant role in the progression of breast cancer. Several studies have demonstrated that Periostin is overexpressed in breast cancer tissues compared to normal breast tissue (1, 2). In addition, breast tumor progression has been shown to be accompanied by increased Periostin expression; researchers could show that elevated Periostin expression in epithelial cells was linked to decreased disease-free survival and overall survival (3). These findings suggest that Periostin plays a significant role in breast tumor progression.

 

High circulating Periostin levels are associated with aggressive breast cancer subtypes and poorer patient prognosis

Periostin is involved in various processes such as tumor growth, invasion, metastasis, and the modulation of the tumor microenvironment (4). High serum Periostin levels have been associated with more aggressive breast cancer subtypes and poorer patient prognosis (5). Periostin promotes tumor cell survival, supports angiogenesis, and facilitates the remodeling of the extracellular matrix, thereby aiding cancer cell dissemination (5).

 

Periostin significantly impacts cancer progression and treatment outcomes

Periostin plays vital roles in tumor development, metastasis, resistance to chemotherapy, and shaping the tumor microenvironment (6). In addition, Periostin contributes to chemotherapy resistance by creating a protective niche for cancer cells (6). In a recent study researchers explored the relationship between Periostin and the tumor microenvironment, highlighting its potential as a promising prognostic biomarker and therapeutic target for addressing tumor progression and chemoresistance (7). In a further study researchers aimed to identify proteins that are overexpressed in tumors with extensive stroma within immune-excluded triple-negative breast cancer, revealing a link between Periostin and elevated tumor stroma along with immune exclusion in triple-negative breast cancer (8).

Periostin can reliably be measured in biological fluids with a conventional ELISA assay

Periostin ELISA Assay Highlights (Cat. No. BI-20433)

• Small sample volume – 10 µl / well
• Reliable – full validation package
• Easy – 7 standards and 2 controls included
• Trusted – widely cited 

 

Download our Periostin Flyer here

 

 

Literature

1. Expression of periostin in human breast cancer. Puglisi F, Puppin C, Pegolo E, Andreetta C, Pascoletti G, D’Aurizio F, Pandolfi M, Fasola G, Piga A, Damante G, Di Loreto C. J Clin Pathol. 2008 Apr;61(4):494-8. doi: 10.1136/jcp.2007.052506. Epub 2007 Oct 15. PMID: 17938160.
2. The expression analysis of periostin in human breast cancer. Zhang Y, Zhang G, Li J, Tao Q, Tang W. J Surg Res. 2010 May 1;160(1):102-6. doi: 10.1016/j.jss.2008.12.042. Epub 2009 Feb 27. PMID: 19524268.
3. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. Kim GE, Lee JS, Park MH, Yoon JH. PLoS One. 2017 Nov 21;12(11):e0187635. doi: 10.1371/journal.pone.0187635. PMID: 29161296; PMCID: PMC5697858.
4. Periostin: biology and function in cancer. Dorafshan S, Razmi M, Safaei S, Gentilin E, Madjd Z, Ghods R. Cancer Cell Int. 2022 Oct 12;22(1):315. doi: 10.1186/s12935-022-02714-8. PMID: 36224629; PMCID: PMC9555118.
5. High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner AK. Breast Cancer Res Treat. 2020 Apr;180(2):515-524. doi: 10.1007/s10549-020-05570-0. Epub 2020 Feb 10. PMID: 32040688.
6. The roles of periostin derived from cancer-associated fibroblasts in tumor progression and treatment response. De Oliveira Macena Y, Cezar MEN, Lira CBF, De Oliveira LBDM, Almeida TN, Costa ADAV, De Araujo BMD, de Almeida Junior D, Dantas HM, De Mélo EC, de Araújo ST, de França Júnior RR, Dos Santos Lemos Gurgel MA, de Carvalho Fraga CA. Cancer Metastasis Rev. 2024 Nov 30;44(1):11. doi: 10.1007/s10555-024-10233-3. PMID: 39614015.
7. The association between periostin and tumor microenvironment: a promising cancer prognostic biomarker and therapeutic target to combat tumor progression and chemoresistance. Nabi-Afjadi M, Farzam F, Soltani S, Golestani N, Asl SS, Aziziyan F, Zalpoor H, Ghasemi F, Dabirmanesh B, Khajeh K. Cancer Cell Int. 2025 Sep 3;25(1):320. doi: 10.1186/s12935-025-03959-9. PMID: 40903761; PMCID: PMC12406393.

Breast Cancer Awareness Month is an international health campaign, dedicated to increasing awareness about screening and prevention for a disease that affects approximately 2.3 million women worldwide (1).

Breast cancer is the most common cancer among women and the leading most common cancer diagnosis (2). Although it mainly affects women, men can also develop malignant breast tissue (3). Male breast cancer is rare, making up about 1% of all cases, but men are often diagnosed at more advanced stages. This delay in seeking medical attention frequently results in later detection and less favorable outcome.

OCTOBER BREAST CANCER AWARENESS MONTH

Detecting breast cancer early greatly enhances the chances of successful treatment, resulting in higher survival rates, less intensive therapies, and improved quality of life. Key early detection strategies include routine mammograms, clinical breast exams, and being attentive (4) .Early detection of breast cancer significantly improves successful outcomes by leading to higher survival rates, less aggressive treatment options, and a better quality of life (4).

Learn about Personalized Early Detection and Prevention of Breast Cancer:

– Breast cancer: A review of risk factors and diagnosis. Medicine (Baltimore). Obeagu EI et al.,  2024.   

– Breast Cancer Awareness Month 2025 UK | Breast Cancer Now

– October is Breast Cancer Awareness Month – American Association of Cancer Research 

– Breast Cancer Awareness Month 2025, World Health Organization

– Personalized early detection and prevention of breast cancer: ENVISION consensus statement. Pashayan N et al.,  2020.

Abstract

The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness-implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas.

 

BIOMEDICA offers fully validated Biomarker ELISA Kits for Breast Cancer Research

PERIOSTIN ▪ NEUROPILIN-1 ▪ OSTEPROTEGERIN ▪ soluble RANKL ▪ SEMAPHORIN 4D ▪ IL-6

click here for more information on our Biomarker ELISAs in Oncology

 

ELISA Assay Kit Highlights

• EASY –ready to use calibrators & controls included (color-coded reagents)
• FULL VALIDATION PACKAGE – assays are optimized for clinical samples
• HIGH QUALITY GUARANTEED – results you can rely on
• WIDELY CITED in over 1000 publications

 

BIOMEDICA – Complete ready-to-use ELISA kits for superior performance and reproducibility

 

 

Literature

1. Breast Cancer Awareness Month 2025, World Health Organization
2. Breast cancer: presentation, investigation and management. Katsura C, Ogunmwonyi I, Kankam HK, Saha S. Br J Hosp Med (Lond). 2022 Feb 2;83(2):1-7. doi: 10.12968/hmed.2021.0459. PMID: 35243878.
3. Male Breast Cancer. Khattab A, Kashyap S, Monga DK. 2024 Sep 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30252292.

 

 

 

World Heart Day 2025 is a global initiative dedicated to raising awareness about cardiovascular health. It highlights the importance of healthy living to prevent heart disease and stroke.  

Biomarkers have revolutionized on how heart diseases are diagnosed and treated. Ongoing research on newer exploratory protein biomarkers may shed light into the complex mechanisms that drive the disease process.

Biomedica offers a range of quality ELISA assay kits for your clinical and preclinical research:

World Heart Day – September 29, 2025

Biomarkers for Heart Disease:  NT-proBNP, NT-proAN`P, Big Endothelin-1, FGF23, LRG1

NT-proBNP  is a biomarker used to assess heart failure and measure the severity of cardiac dysfunction. Elevated levels of NT-proBNP indicate increased stress on the heart (1).

NT-proANP (N-terminal pro-atrial natriuretic peptide) is a biomarker released by the heart in response to atrial stretch and increased blood volume. It is used clinically to assess heart failure and identify cardiac stress, aiding in diagnosis and management of cardiovascular conditions (2).

Big Endothelin-1 is an inactive precursor of endothelin-1, a potent vasoconstrictor involved in regulating blood vessel tone and blood pressure. Elevated levels of Big Endothelin-1 are associated with cardiovascular diseases such as hypertension and heart failure (3).

FGF23 (Fibroblast Growth Factor 23) is a hormone primarily involved in regulating phosphate metabolism and vitamin D levels. It helps maintain mineral balance by reducing phosphate reabsorption in the kidneys and suppressing vitamin D activation. Elevated FGF23 levels are linked to cardiovascular disease and chronic kidney disease (4).

Leucine-rich alpha-2-glycoprotein (LRG) is a plasma protein involved in immune response and inflammation. It plays a role in modulating immune cell activity and has been studied as a potential biomarker for various inflammatory and infectious conditions (5).

 

Biomedica offers a range of quality ELISA assay kits for your clinical and preclinical research:

-NT-proBNP (Cat. No. BI-1204), Rat NT-proBNP (Cat. No. BI-1204R)

-NT-proANP (Cat. No. BI-20892) (human  and non-human (rat, mouse.. ) use

-Big Endothelin-1 (Cat. No. BI-20082H)

-FGF23 intact (Cat. No. BI-20700)

-FGF23 c-terminal (Cat. No.  BI-20702)

-LRG (Cat. No. BI-LRG)

 

Literature 

1. BNP and NT-proBNP as prognostic biomarkers for the prediction of adverse outcomes in HFpEF patients: A systematic review and meta-analysis. Ammar LA, Massoud GP, Chidiac C, Booz GW, Altara R, Zouein FA. Heart Fail Rev. 2025 Jan;30(1):45-54. doi: 10.1007/s10741-024-10442-6. Epub 2024 Oct 7. PMID: 39373821; PMCID: PMC12002167.
2. Prognostic value of NT-proANP levels on major cardiovascular outcomes in a 31-year follow-up study depends on baseline morbidity. Sakko S, Perkiömäki J, Ylitalo A, Huikuri H, Ukkola O, Koivunen P, Tapio J. Sci Rep. 2025 May 28;15(1):18660. doi: 10.1038/s41598-025-03819-6. PMID: 40436983; PMCID: PMC12119872.
3. Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure. Wang J, Feng J, Tse G, Zhai M, Huang Y, Zhou Q, Zhuang X, Liu H, Zhang Y, Zhang J. Korean Circ J. 2025 Aug;55(8):705-717. doi: 10.4070/kcj.2024.0354. Epub 2025 Apr 11. PMID: 40345830; PMCID: PMC12314060.
4. Network Interactions of Circulating FGF23, HRG-HMGB1, and Cardiac Disease in CKD. Perwad F, Akwo EA, Singhal A, Vartanian N, Suva LJ, Friedman PA, Robinson-Cohen C. J Am Soc Nephrol. 2025 Apr 16. doi: 10.1681/ASN.0000000710. Epub ahead of print. PMID: 40238264.
5. Leucine-rich alpha-2 glycoprotein as a potential biomarker for large vessel vasculitides. Umezawa N, Mizoguchi F, Maejima Y, Kimura N, Hasegawa H, Hosoya T, Fujimoto M, Kohsaka H, Naka T, Yasuda S. Front Med (Lausanne). 2023 May 5;10:1153883. doi: 10.3389/fmed.2023.1153883. PMID: 37215715; PMCID: PMC10196172.

Our EZ4U (easy for you) cell proliferation and cytotoxicity assay was highlighted in a recent study that investigated the use of peptidomimetics, selected synthetic small-molecule compounds, as a therapeutic approach for the targeted treatment of neurodegenerative conditions such as Alzheimer’s disease.

The use of selected peptidomimetics has shown strong inhibitory effects on amyloid protein aggregation, highlighting their potential as promising therapeutic candidates.

Alzheimer´s Research with EZ4U Cell Viability Assay

Protective Effect of a Hexapeptide Derived from Rotifer-Specific SCO-Spondin Against Beta-Amyloid Toxicity. Datki Z, Sinka R, Dingmann BJ, Galik B, Szabo A, Galik-Olah Z, Toth GK, Bozso Z. Int J Mol Sci. 2025 May 26;26(11):5109. doi: 10.3390/ijms26115109. PMID: 40507923; PMCID: PMC12154537.

Abstract

The Rotimer (rotifer-specific biopolymer) like SCO-spondin (R-SSPO/1), predicted as the main component of this biopolymer, is an adequate base for the design of functional small peptides. This macromolecule is interactive and protective against neurotoxic human-type beta-amyloid 1-42 aggregates (agg-Aβ). The current work presents biological investigations and predictable molecular interaction analysis of DSSNDL and PNCRDGSDE peptides that were synthesized based on the sequences of R-SSPO/1. Viability assays (NADH-dependent cellular reduction capacity, intracellular esterase activity, and motility) were performed on differentiated neuro-type cell cultures (SH-SY5Y and PC12) and on Rotimer-depleted rotifers (Euchlanis dilatata and Lecane bulla). A control peptide (STTRPTGTT), not found in Rotimer, was also included in the study. All three peptides are present in both rotifer and human proteomes. Among these small molecules, DSSNDL showed a significant protective effect against the toxicity of agg-Aβ both in vitro and in vivo and presumably interacted with its aggregates. The stagogram analysis of amyloid-peptide complexes and the possible bonding competition of these small molecules against aggregation-specific dyes on agg-Aβ surface suggest that DSSNDL affects the properties of these neurotoxic macromolecules. This effective hexapeptide can serve as a promising candidate for further investigations into the inactivation of beta-amyloid toxicity.

Analysis of Cell Viability

The toxicity of aggregated Aβ and the impact of potential antagonistic peptides were examined. Mitochondrial and cytoplasmic reduction capacities were assessed using the EZ4U kit, which measures soluble formazan produced after 4 hours of incubation; the absorbance at 490/630 nm correlates with cell viability in the samples.

 

Alzheimer´s Research with EZ4U Cell Viability Assay

EZ4U Kit (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

 

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!

 

Discover our Biomarker ELISA Kit Collection

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)
• FULL VALIDATION PACKAGE – assays are optimized for clinical samples following high level international quality standards.
• HIGH QUALITY GUARANTEED – results you can rely on
• 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. 

 

Biomedica also offers Custom Analytical Service Measurements

• ELISA & LUMINEX
• NEXT-GENERATION SEQUENCING
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“ We have been using the Biomedica ELISA kits for measurements of OPG and soluble RANKL in several contexts and are very pleased with how well they perform both in terms of specificity and reproducibility. For the RANKL kit the measurements are validated by no measurable free soluble RANKL when analyzing culture media where a RANKL inhibitor has been added. Furthermore, we have measured the proteins in a range of human body fluids as well as in tissue and cell culture media and the kits work both when larger and smaller concentrations are measured and when samples are diluted. Martin Blomberg Jensen, MD, DMSc, Andrologist, Dept.Growth and Reproduction 5064, Rigshospitalet, Denmark.”

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Our custom sample testing services are designed to meet the unique needs of your business by providing accurate, reliable, and comprehensive testing solutions tailored to your specific requirements.

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• Tailored Testing Protocols:  testing procedures customized to your specifications
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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.