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• SCLEROSTIN - a biomarker for predicting the onset of frailty

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

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

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

 

SCLEROSTIN – a biomarker for predicting the onset of frailty

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

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

SCLEROSTIN – a biomarker for predicting the onset of frailty

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

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

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

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

 

Literature

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

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Exciting research news! The BIOMEDICA bioactive Sclerostin and Periostin ELISA kits were used in a groundbreaking study evaluating the association of these bone proteins related to cardiovascular disease (CVD), with the main vascular risk scales in patients with type 2 diabetes.

All Biomedica ELISA assays are fully validated following international quality guidelines.

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

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• LOW sample volume – 20µl sample /well 

 

Sclerostin ELISA (cat. no. BI-20492)

• TRUSTED – most referenced Sclerostin ELISA (+280 citations)
• LOW sample volume – 20µl sample /well

 

Periostin ELISA (cat. no. BI-20433)

• LOW sample volume – 20µl sample /well
• SPECIFIC – Characterized, epitope mapped capture and detection antibodies:

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier, E et al.

 

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Type 2 diabetes is linked to an elevated risk of cardiovascular disease (CVD), affecting approximately 35% of patients with the condition (1). As a result, assessing cardiovascular risk is essential for effective disease management in individuals with type 2 diabetes. Various risk scores have been developed to estimate CVD in the general population, including the Framingham Risk Score (FRS), the REGICOR and more recently, the SCORE2-Diabetes was introduced, specifically tailored for individuals with type 2 diabetes (2).

While these computational tools are utilized in clinical practice, there remains a need to investigate new biomarkers that could enhance cardiovascular risk stratification for patients with type 2 diabetes.

Typical bone proteins, including Sclerostin and Periostin, have been linked to cardiovascular disease (CVD). Concurrently, various risk scores have been created to forecast CVD in the general population. The objective of the following study was to examine the relationship between these bone proteins connected to CVD and key vascular risk scales:

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

Key findings:

• Sclerostin and Periostin are associated with vascular risk in the SCORE2-Diabetes algorithm.
• This suggests that Sclerostin and Periostin may serve as useful diagnostic biomarkers for vascular risk in patients with type 2 diabetes.
• Future prospective studies are needed to validate the significance of these bone proteins in assessing vascular risk in the diabetic population.

 

Abstract

Background: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population.

Methods: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed.

Results: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity.

Conclusions: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.

 

Literature

1. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB. Cardiovasc Diabetol. 2022 May 14;21(1):74. doi: 10.1186/s12933-022-01516-6. PMID: 35568946.
2. Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S, García-Martín A, García-Fontana B, Martínez-Heredia L, García-Fontana C, Muñoz-Torres M. Cardiovasc Diabetol. 2024 Aug 24;23(1):311. doi: 10.1186/s12933-024-02406-9. PMID: 39182106.

 

 

November is Diabetes Awareness Month bringing attention to diabetes and its impact on millions of individuals.

Diabetes mellitus has emerged as the third most significant non-communicable disease, following cardiovascular diseases and cancer. This condition encompasses a group of metabolic disorders marked by chronic hyperglycemia resulting from various causes, along with inadequate insulin secretion and impaired insulin action. According to the most recent statistics from the International Diabetes Federation, the global number of individuals with diabetes reached 530 million in 2021, with projections suggesting it could exceed 780 million by 2045. Due to the long-term nature of the disease, diabetes can lead to damage across multiple body systems or organs, resulting in various complications (1, 2). Beyond the more commonly known complications of diabetes such as heart disease, diabetes can also affect the skeletal system. This severe complication of diabetes leads to bone loss potentially resulting in osteoporosis and increased fracture risk.

Identifying biomarkers that may predict fracture risk in individuals with diabetes is crucial for improving patient care.

Sclerostin and Fracture Risk Prediction in Diabetes

Sclerostin (SOST) is a bone-related protein that is mainly produced by osteocytes, bone cells embedded in the bone matrix. Sclerostin is considered to be one of the major regulators of bone formation. It is a soluble antagonist of the Wnt signaling pathway and its inactivation leads to bone degradation, while the  of Wnt signaling promotes bone formation (3). Sclerostin has been a target of therapeutic antibodies for osteoporosis treatment due to its role in inhibiting bone formation.

Bone as an endocrine organ

Research indicates that bone, which is involved in lipid and glucose metabolism, is increasingly recognized as an endocrine organ. Recent findings suggest that sclerostin contributes to disorders related to lipid and glucose metabolism (4). Studies have shown that Sclerostin levels are increased in individuals with prediabetes and correlated with insulin resistance in the skeletal muscle, liver, and adipose tissue (5). In addition, Sclerostin levels have been shown to be negatively associated with insulin sensitivity in obese but not in lead woman (6).

Further studies have revealed that increased serum Sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus (7, 8). Sclerostin, has also been suggested to have predictive value for fracture risk in patients with diabetes (9).

Sclerostin – a promising circulating marker of diabetic bone disease

Sclerostin has emerged as a promising circulating marker of diabetic bone disease. It may not only reflect the degree of osteocyte dysfunction and the suppression of bone formation that occurs in this disease, but it may also potentially reflect the vascular alterations that are associated with specific bone alterations such as cortical porosity (10).

Additional research is essential to enhance the understanding of biochemical markers in the assessment of diabetic bone disease. Specifically, the ability of bone markers to forecast fracture risk needs further examination.

Circulating Sclerostin levels can reliably be measured in human serum and plasma samples with a conventional SCLEROSTIN ELISA Assay Kit.

Sclerostin ELISA (cat. no. BI-20492)

• MOST referenced in more than 300 citations
• LOW sample volume – 20µl sample /well
• For SERUM & PLASMA samples
• RELIABLE – full validation package

 

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

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• RIGOROUSLY validated for clinical samples
• LOW sample volume – 20µl sample /well
• RELIABLE – full validation package

 

Literature

1. International Diabetes Federation – Facts and Figures
2. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Hossain MJ, Al-Mamun M, Islam MR. Health Sci Rep. 2024; 7(3):e2004. doi: 10.1002/hsr2.2004. PMID: 38524769.
3. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F, Giusti F, Palmini G, Brandi ML. Osteoporos Int. 2023; 34(2):213-238. doi: 10.1007/s00198-022-06523-7. PMID: 35982318.
4. The role of sclerostin in lipid and glucose metabolism disorders. Jiang H, Li D, Han Y, Li N, Tao X, et al., Biochem Pharmacol. 2023; 215:115694. doi: 10.1016/j.bcp.2023.115694. PMID: 37481136.
5. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, Tripathy D, Jenkinson C, Folli F. Diabetes Care. 2015; 38(8):1509-17. doi: 10.2337/dc14-2989. PMID: 26084344.
6. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A, Meijer R, van Raalte D, den Heijer M, Heijboer A, de Jongh R. Endocr Connect. 2021; 10(2):131-138. doi: 10.1530/EC-20-0535. PMID: 33480863.
7. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. M.S. Ardawi, D.H. Akhbar, A. Alshaikh, M.M. Ahmed, M.H. Qari, A.A. Rouzi, et al. Bone, 56 (2013), pp. 355-362
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; 98(10):4030-7. doi: 10.1210/jc.2013-2143. PMID: 23894157.
9. Fracture risk assessment in diabetes mellitus. Front Endocrinol (Lausanne). Chen W, Mao M, Fang J, Xie Y, Rui Y. 2022; 13:961761. doi: 10.3389/fendo.2022.961761. PMID: 36120431.
10. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, El-Hajj Fuleihan G, Ferrari S. J Clin Endocrinol Metab. 2023; 108(10):e923–36. doi: 10.1210/clinem/dgad255. PMID: 37155585.

 

 

The Biomedica SCLEROSTIN ELISA Assay Kit (# BI-20492) was utilized in a recent publication assessing the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. Read more: Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy.

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

• Most referenced Sclerostin ELISA in over 290 citations
• Low sample volume – 20µl / well
• Validation following international guidelines

 

Sclerostin a biomarker in renal pediatric bone disease

Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy. Laster M. et al., Nutrients. 2023 Sep 25;15(19):4127. doi: 10.3390/nu15194127. PMID: 37836411; PMCID: PMC10574198 . link to full text

Abstract

The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not well understood. Specific factors secreted by osteocytes are elevated in the serum of adults and pediatric patients with CKD-MBD, including FGF-23 and sclerostin, a known inhibitor of the Wnt signaling pathway. The molecular mechanisms that promote bone disease during the progression of CKD are incompletely understood. In this study, we performed a cross-sectional analysis of 87 pediatric patients with pre-dialysis CKD and post-dialysis (CKD 5D). We assessed the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. We report that serum sclerostin levels were elevated in both early and late CKD. Higher circulating and bone sclerostin levels were associated with histomorphometric parameters of bone turnover and mineralization. Immunofluorescence analyses of bone biopsies evaluated osteocyte staining of antibodies towards the canonical Wnt target, β-catenin, in the phosphorylated (inhibited) or unphosphorylated (active) forms. Bone sclerostin was found to be colocalized with phosphorylated β-catenin, which suggests that Wnt signaling was inhibited. In patients with low serum sclerostin levels, increased unphosphorylated “active” β-catenin staining was observed in osteocytes. These data provide new mechanistic insight into the pathogenesis of CKD-MBD and suggest that sclerostin may offer a potential biomarker or therapeutic target in pediatric renal osteodystrophy.

 

Related Literature

FGF-23 and sclerostin in serum and bone of CKD patients. Lima F, Monier-Faugere MC, Mawad H, David V, Malluche HH. Clin Nephrol. 2023 May;99(5):209-218. doi: 10.5414/CN111111. PMID: 36970967; PMCID: PMC10286735. (Biomedica Sclerostin ELISA Assay Kit, cat. no. BI-20492 citation)

Sclerostin and Dickkopf-1 in renal osteodystrophy. Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH. Clin J Am Soc Nephrol. 2011 Apr;6(4):877-82. doi: 10.2215/CJN.06550810. Epub 2010 Dec 16. PMID: 21164019; PMCID: PMC3069382. (Biomedica Sclerostin ELISA Assay Kit, cat. no. BI-20492 citation)

Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review. Capossela L, Ferretti S, D’Alonzo S, Di Sarno L, Pansini V, Curatola A, Chiaretti A, Gatto A.Biology (Basel). 2023 Nov 2;12(11):1395. doi: 10.3390/biology12111395. PMID: 37997994; PMCID: PMC10669025.

 

Type 2 diabetes mellitus (T2DM) is characterized by a persistent state of elevated blood sugar levels and glucose intolerance, resulting from the body´s incomplete response to insulin, accompanied by an increase in insulin production and a subsequent insulin deficiency. Individuals suffering from T2DM have an increased risk of cardiovascular disease (CVD). High glucose levels, insulin resistance, and chronic inflammation, contribute to endothelial dysfunction (ED) and atherosclerosis (1). ED refers to an impairment of the endothelium, the inner lining of blood vessels, which play an important role in regulating vascular health.

Sclerostin is associated with endothelial dysfunction in patients with type 2 diabetes

Sclerostin is a protein known primarily for its role in bone metabolism. It has also been identified of being linked to endothelial dysfunction in individuals diagnosed with type 2 diabetes (2). Sclerostin is predominantly secreted by osteocytes, cells that are embedded in the bone. However, vascular endothelial cells have also been observed to produce sclerostin leading to the discovery of its significant anti-calcifying role (3).

Sclerostin is associated with endothelial dysfunction in patients with type 2 diabetes: In an investigation in individuals with T2DM, researchers measured endothelial dysfunction by digital thermal monitoring (2). This method is a valid and noninvasive technique to evaluate endothelial function using temperature change on finger as a surrogate measure of the magnitude of vascular reactivity index (VRI) (4) . Serum Sclerostin levels were measured in the T2DM cohort with the Biomedica ELISA.  The prospective cross-sectional study revealed that serum sclerostin levels are positively associated with endothelial dysfunction measured in patients with T2DM.

A previous cross-sectional study in patients with T2DM, with/without cardiovascular disease, determined Sclerostin levels and its expression by RT-qPCR and immunohistochemistry in calcified and non-calcified artery of the lower limb from T2D. Serum Sclerostin was measured with an ELISA from Biomedica. Moreover, in vitro experiments were performed in vascular smooth muscle cells under calcifying conditions investigating the cardioprotective function of Sclerostin (5). The study provided evidence that supports the protective function of Sclerostin in the development of vascular calcification. The findings suggest that Sclerostin could potentially reduce the susceptibility to atherosclerosis by decreasing atherosclerotic plaque formation and underscore the significance of the bone-vascular axis when developing therapeutic strategies for treating impaired bone metabolism or vascular diseases (5).

Features and Benefits when measuring Sclerostin with the Biomedica ELISA kits

Sclerostin ELISA, #BI-20492

• TRUSTED – most referenced Sclerostin ELISA (+280 citations)
• LOW sample volume – 20µl sample /well
• For SERUM & PLASMA samples
• RELIABLE – fully validated  following international quality guidelines

 

 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. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Garcia-de Los Ríos C, Medina-Casado M, Díaz-Chamorro A, Sierras-Jiménez M, Lardelli-Claret P, Sclerostin as a biomarker of cardiovascular risk in women with systemic lupus erythematosus. Cáliz-Cáliz R, Sabio JM. Sci Rep. 2022 Dec 14;12(1):21621. doi: 10.1038/s41598-022-25651-y. PMID: 36517533; PMCID: PMC9749620. Gimbrone MA Jr, García-Cardeña G. Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301. PMID: 26892962; PMCID: PMC4762052.
2. Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study. Hsu BG, Wu DA, Yang HY, Chen MC.Medicine (Baltimore). 2023 Sep 8;102(36):e34649. doi: 10.1097/MD.0000000000034649. PMID: 37682176; PMCID: PMC10489308.
3. Sclerostin Protects Against Vascular Calcification Development in Mice. De Maré A, Opdebeeck B, Neven E, D’Haese PC, Verhulst A J Bone Miner Res. 2022 Apr;37(4):687-699. doi: 10.1002/jbmr.4503. Epub 2022 Feb 15. PMID: 35038187; PMCID: PMC9303214.
4. Digital thermal monitoring techniques to assess vascular reactivity following finger and brachial occlusions. Heath M, Gourley D, Naghavi M, Klies S, Tanaka H. J Clin Hypertens (Greenwich). 2020 Dec 7;23(1):122–7. doi: 10.1111/jch.14115. PMCID: PMC8030097.
5. Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells. González-Salvatierra S, García-Fontana C, Lacal J, Andújar-Vera F, Martínez-Heredia L, Sanabria-de la Torre R, Ferrer-Millán M, Moratalla-Aranda E, Muñoz-Torres M, García-Fontana B. Cardiovasc Diabetol. 2023 Nov 2;22(1):301. doi: 10.1186/s12933-023-02043-8. PMID: 37919715; PMCID: PMC10623848.

November is “Diabetes Awareness Month” raising attention to this fast growing and life-threating epidemic. Patients suffering from diabetes have a risk of additional health complications, including heart disease, strokes, and diabetic kidney disease (DKD). People who develop DKD mostly have few symptoms in the early stage of the disease, although the risk of developing severe kidney damage is very high. High blood sugar levels may damage the small blood vessels in the kidney leading to kidney damage, kidney failure, and high blood pressure (1). 

FGF23 and Sclerostin – novel biomarkers in diabetic kidney disease

Traditionally, the bone is regarded as a structural organ that gives the human body support and facilitates physical movement. However, bone is also a source of various hormones including fibroblast growth factor 23 and sclerostin that play an important role in regulating glucose metabolism and DKD (2).

FGF23 and Sclerostin  – novel biomarkers in diabetic kidney disease

 

FGF23 and Sclerostin – bone derived hormones regulate glucose metabolism

 

Fibroblast growth factor 23 (FGF23) is a bone-derived protein that regulates phosphate metabolism, by inhibiting renal phosphate reabsorption. There is increasing evidence that FGF23 plays a role in type 2 diabetes (T2DM), as FGF23 levels are elevated in these patients, even in individuals with preserved kidney function when compared to the general population (3). Phosphate independent effects on FGF23 following glucose loading were shown in a recent study demonstrating that FGF23 is associated with glucose, insulin and proinsulin levels, as well as obesity (4 ). Furthermore, FGF23 has also been shown to be associated with the development of gestational diabetes mellitus (5).

Sclerostin is a protein that is produced by bone cells that inhibits bone formation. Recent research suggests that Sclerostin also plays a role in lipid and glucose metabolism as serum sclerostin is negatively associated with insulin sensitivity as measured in obese, but not lean women (5). Sclerostin levels have also been shown to be increased in individuals with prediabetes (6).

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

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

• RELIABLE – validated following international quality guidelines
• CITED in over 60 publications
• EASY – 8 standards and 2 controls included
• For SERUM & PLASMA samples
• HIGH QUALITY guaranteed!

 

Sclerostin ELISA, #BI-20492

• MOST referenced in more than 280 citations
• LOW sample volume – 20µl sample /well
• For SERUM & PLASMA samples
• RELIABLE – full validation package

 

Bioactive Sclerostin ELISA, BI-20472

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

 

Literature

1. Renal microvascular disease predicts renal function in diabetes. Futrakul N, Futrakul P. Ren Fail. 2012;34(1):126-9. doi: 10.3109/0886022X.2011.623490. Epub 2011 Oct 20. PMID: 22010784.
2. The Emerging Role of Bone-Derived Hormones in Diabetes Mellitus and Diabetic Kidney Disease. Li Y, Gu Z, Wang J, Wang Y, Chen X, Dong B. Front Endocrinol (Lausanne). 2022 Jul 11;13:938830. doi: 10.3389/fendo.2022.938830. PMID: 35966090; PMCID: PMC9367194.
3. Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease Wahl P., Xie H., Scialla J., Anderson C.A.M., Bellovich K., Brecklin C.et al.. (2012)  Diabetes Care 35, 994–1001 10.2337/dc11-2235 
4. Fibroblast Growth Factor 23, Glucose Homeostasis, and Incident Diabetes: Findings of 2 Cohort Studies, Amarens van der Vaart, Coby Eelderink, André P van Beek, Stephan J L Bakker, Peter R van Dijk, Martin H de Borst, The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 10, October 2023, Pages e971–e978, https://doi.org/10.1210/clinem/dgad246.
5. Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus. Hocher CF, Chen X, Zuo J, Horvathova K, Hocher B, Krämer BK, Chu C. Diabetes Metab Res Rev. 2023 Aug 8:e3704. doi: 10.1002/dmrr.3704. Epub ahead of print. PMID: 37553983.
6. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A, Meijer R, van Raalte D, den Heijer M, Heijboer A, de Jongh R. Endocr Connect. 2021 Feb;10(2):131-138. doi: 10.1530/EC-20-0535. PMID: 33480863; PMCID: PMC7983521.
7. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, Tripathy D, Jenkinson C, Folli F. Diabetes Care. 2015 Aug;38(8):1509-17. doi: 10.2337/dc14-2989. Epub 2015 Jun 17. PMID: 26084344.

Bone markers are currently used to monitor skeletal diseases and treatments. The proteins Sclerostin and Dickkopf-1 (DKK-1) reflect distinct biological processes and have gained attention as potential biomarkers for bone-related conditions. They may provide valuable information for diagnosis, prognosis, and monitoring of bone diseases and treatments.

Sclerostin and DKK-1 emerging biomarkers for bone disease

Sclerostin and Dickkkopf-1 are two important osteocyte proteins that are involved in the regulation of bone metabolism, particularly through their interactions with the Wnt signaling pathway.

SCLEROSTIN (SOST) is a glycoprotein that is primarily secreted by osteocytes, the most abundant cells in bone tissue. It inhibits Wnt signaling, which is a critical pathway regulating bone formation and remodeling. Sclerostin acts as a negative regulator of bone formation by binding to the LRP5/6 co-receptors (low-density lipoprotein receptor protein), which activate Wnt signaling. By binding to LRP5/6, sclerostin inhibits the interaction between Wnt ligands and the Frizzled receptor, thereby inhibiting Wnt signaling and suppressing bone formation. Inhibition of Sclerostin has led to the development of a novel anabolic therapy for osteoporosis.

DICKKOPF-1 (DKK-1) is a protein that also inhibits the Wnt signaling pathway. DKK-1 binds to the LRP5/6 co-receptors thereby preventing Wnt ligand interaction thus inhibiting bone formation and promoting bone resorption.

The Wnt-signaling pathway is one of the most important pathways controlling bone metabolism. Sclerostin and Dickkopf-1 act as Wnt inhibitors and play a crucial role in controlling bone formation and resorption.

Sclerostin and DKK-1 can easily be measured in blood samples with an ELISA assay

BIOMEDICA offers two kits to measure Sclerostin

Bioactive Sclerostin ELISA cat. no. BI-20472

• serum, plasma, cell-culture
• characterized antibodies
• day test
• 20µl sample volume
• sample values provided
• full validation package

 

The epitope of the monoclonal capture antibody is in loop 2 of the Sclerostin molecule, which is the binding site for the LRP5/6 complex.

All Sclerostin molecules including potential fragments containing this receptor binding region can be detected.

Bioactive Sclerostin ELISA – antibody binding sites

 

Sclerostin ELISA cat. no. BI-20492

• most referenced more than 280 citations
• 20µl sample volume
• for serum, plasma
• full validation package

 

DKK-1 ELISA cat. no. BI-20413

• widely cited
• day test
• no sample dilution
• full validation package

 

All assays are developed and manufactured by BIOMEDICA

Related Publications

New Emerging Biomarkers for Bone Disease: Sclerostin and Dickkopf-1 (DKK1). Dincel AS, Jørgensen NR; IOF-IFCC Joint Committee on Bone Metabolism (C-BM). Calcif Tissue Int. 2023 Feb;112(2):243-257. doi: 10.1007/s00223-022-01020-9. Epub 2022 Sep 27. PMID: 36165920.

Abstract

A healthy skeleton depends on a continuous renewal and maintenance of the bone tissue. The process of bone remodeling is highly controlled and consists of a fine-tuned balance between bone formation and bone resorption. Biochemical markers of bone turnover are already in use for monitoring diseases and treatment involving the skeletal system, but novel biomarkers reflecting specific biological processes in bone and interacting tissues may prove useful for diagnostic, prognostic, and monitoring purposes. The Wnt-signaling pathway is one of the most important pathways controlling bone metabolism and consequently the action of inhibitors of the pathway such as sclerostin and Dickkopf-related protein 1 (DKK1) have crucial roles in controlling bone formation and resorption. Thus, they might be potential markers for clinical use as they reflect a number of physiological and pathophysiological events in bone and in the cross-talk with other tissues in the human body. This review focuses on the clinical utility of measurements of circulating sclerostin and DKK1 levels based on preanalytical and analytical considerations and on evidence obtained from published clinical studies. While accumulating evidence points to clear associations with a number of disease states for the two markers, and thus, the potential for especially sclerostin as a biochemical marker that may be used clinically, the lack of standardization or harmonization of the assays still hampers the clinical utility of the markers.

 

Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration. Nelson AL, Fontana G, Miclau E, Rongstad M, Murphy W, Huard J, Ehrhart N, Bahney C. J Tissue Eng Regen Med. 2022 Nov;16(11):961-976. doi: 10.1002/term.3349. Epub 2022 Sep 16. PMID: 36112528; PMCID: PMC9826348.

Decrease of bone biomarker Sclerostin in women with anorexia nervosa during nutrition therapy – indication of reduced bone loss

Anorexia nervosa (AN) is an eating disorder and has one of the highest mortality rates of any mental illness.  It affects roughly 2.9 million people and many experience bone loss and increased fracture risk. In a 3-year prospective study, Swedish researchers looked into the long-term effects of nutrition therapy. They  investigated bone and mineral metabolism and biomarkers young women with AN. Their results showed that body mass index (BMI) and fat mass was increased. The regulatory bone biomarker Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss.

Read more: Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.

Biomedica Sclerostin ELISA kit 

• The internationally most referenced Sclerostin ELISA with more than 270 citations!
• Rigorously validated according to international quality guidelines
• Low sample volume

 

Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.

Svedlund A, Pettersson C, Tubic B, Ellegård L, Elfvin A, Magnusson P, Swolin-Eide D. J Bone Miner Metab. 2022 Aug 12. doi: 10.1007/s00774-022-01359-x. Epub ahead of print. PMID: 35960382.

Abstract

Introduction: Anorexia nervosa (AN) increases the risk of impaired bone health, low areal bone mineral density (aBMD), and subsequent fractures. This prospective study investigated the long-term effects of bone and mineral metabolism on bone and biomarkers in 22 women with AN.

Materials and methods: Body composition and aBMD were measured by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography. Total and free 25-hydroxyvitamin D (25OHD), C-terminal collagen cross-links (CTX), osteocalcin, bone-specific alkaline phosphatase (BALP), leptin, sclerostin, and oxidized/non-oxidized parathyroid hormone (PTH) were analyzed before and after 12 weeks of intensive nutrition therapy and again 3 years later. An age-matched comparison group of 17 healthy women was recruited for the 3-year follow-up.

Results: Body mass index (BMI) and fat mass increased from baseline to 3 years in women with AN. Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss. CTX was elevated at baseline and after 12 weeks but decreased over 3 years. BALP increased during nutrition therapy and stabilized over 3 years. Free 25OHD was stable during treatment but decreased over 3 years. Non-oxidized PTH was stable during treatment but increased over 3 years. Trabecular volumetric BMD in AN patients decreased during the first 12 weeks and over 3 years despite stable BMI and bone biomarkers implying increased BMD.

Conclusion: Our findings highlight the importance of early detection and organized long-term follow-up of bone health in young women with a history of AN.

Keywords: DXA; Eating disorder; Osteoporosis; Sclerostin; Vitamin D

Related publications

Anorexia nervosa: 30-year outcome.

Dobrescu SR, Dinkler L, Gillberg C, Råstam M, Gillberg C, Wentz E. Br J Psychiatry. 2020 Feb;216(2):97-104. doi: 10.1192/bjp.2019.113. PMID: 31113504; PMCID: PMC7557598.

Abstract

Background: Little is known about the long-term outcome of anorexia nervosa.

Aims: To study the 30-year outcome of adolescent-onset anorexia nervosa. 

Method: All 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971-1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed. 

Results: At the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism.

Conclusions: This long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.

Anorexia Nervosa.

Mitchell JE, Peterson CB. N Engl J Med. 2020 Apr 2;382(14):1343-1351. doi: 10.1056/NEJMcp1803175. PMID: 32242359.

 

Effect of Sclerostin Inhibition on Cardiovascular Safety for the Treatment of Severe Osteoporosis

Osteoporosis is a skeletal disorder characterized by diminished bone strength that is responsible for an increased fracture risk. The glycoprotein sclerostin acts as an inhibitor of bone formation. Therapies directed against this molecule have been developed. A humanized antibody against sclerostin has been approved for the treatment of severe osteoporosis in postmenopausal women in many parts of the world. A recent review by Langdahl BL and colleagues sumarizes the current knowledge of the effect of sclerostin inhibition on cardiovascular safety.

Cardiovascular Safety and Sclerostin Inhibition – a mini-review.
Langdahl BL, Hofbauer LC, Forfar JC. J Clin Endocrinol Metab. 2021 Mar 23:dgab193. doi: 10.1210/clinem/dgab193. Epub ahead of print. PMID: 33755157. 

Biomedica´s Sclerostin ELISA kit:
• The internationally most referenced Sclerostin ELISA!
• Rigorously validated according to FDA/ICH/EMEA guidelines
• Low sample volume

 

RELATED Publications – Sclerostin Inhibition and Cardiovascular Safety

 

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics.

Bovijn J, Krebs K, Chen CY, Boxall R, Censin JC, Ferreira T, Pulit SL, Glastonbury CA, Laber S, Millwood IY, Lin K, Li L, Chen Z, Milani L, Smith GD, Walters RG, Mägi R, Neale BM, Lindgren CM, Holmes MV. Sci Transl Med. 2020 Jun 24;12(549):eaay6570. doi: 10.1126/scitranslmed.aay6570. PMID: 32581134; PMCID: PMC7116615.

Abstract

The glycoprotein Sclerostin is mainly secreted by osteocytes and acts as a negative regulator of bone mass and strength by inhibiting bone formation. Studies have shown that high intensity exercise induces an increase in serum Sclerostin levels suggesting that it may be a key protein involved in muscle and bone interaction.
A recent study by Śliwicka E and colleagues https://buff.ly/3qx6V4U evaluated the effects of a marathon race on selected myokines and Sclerostin in male recreational runners. Results show that in response to the marathon run, a complex network of endocrine interactions is initiated. Further research is needed to fully elucidate the long-term impact of prolonged high intensity exercise on the human body.
Exercise-induced increase in sclerostin- related finding: https://buff.ly/3atiBA4

Check out the Biomedica Sclerostin ELISA kit https://buff.ly/2N4iVsK

• The internationally most referenced Sclerostin ELISA!

• Rigorously validated according to FDA/ICH/EMEA guidelines

• Low sample volume

Biomedica’s Sclerostin ELISA:  

√ HIGH QUALITY – fully validated assay according to ICH/FDA/EMEA guidelines

√ LOW SAMPLE VOLUME – only 20 µl sample / well

√ EASY – convenient ready to use protocol 

√ MOST REFERENCED

 

Also available: Bioactive Sclerostin ELISA

√ specific antibodies targeting the receptor binging region 

 

Complete ready to use ELISA kits for superior performance and reproducibility.

Related ELISAs: free soluble RANKL, OPG, DKK-1, FGF23 – Analytical Service Measurements

Planning your study? Contact us by e-mail or phone to receive your special study quote.

Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis. Sclerostin, a glycoprotein secreted mainly by osteocytes, regulates bone mass by decreasing bone formation.

In patients with hepatic cirrhosis, areal bone mineral density (aBMD) is decreased especially at the lumbar spine. aBMD alone can be insufficient to explain increased fracture risk and bone microarchitecture can provide additional information. However, since assessment of bone microarchitecture is complex, biomarkers could help assess fracture risk. In a study of several biomarkers, Wakolbinger et al. found a correlation between sclerostin and altered bone microarchitecture in hepatic cirrhosis https://link.springer.com/article/10.1007/s00508-019-01595-8.

Biomedica´s bioactive sclerostin ELISA  measures bioactive sclerostin by using a monoclonal antibody directed at the LRP5/6 binding region, capturing all circulating sclerostin forms containing the free-receptor binding site. It is validated in depth according to FDA quality standards, to ensure the ELISA reliability.

Researchers have identified the soluble WNT pathway inhibitor SCLEROSTIN as an independent risk factor for all-cause #mortality in patients after kidney transplantation.
600 stable renal transplant recipients were followed for all-cause mortality for 3 years.

Sclerostin is an independent risk factor for all-cause mortality in kidney transplant recipients.
Zeng S et al., Clin Exp Nephrology (2020). Click link for full text.

Biomedica Sclerostin ELISA: https://www.bmgrp.com/product/cardiovascular/sclerostin-elisa-human-sost-biomedica/

√ HIGH QUALITY – fully validated assay according to ICH/FDA/EMEA guidelines
√ LOW SAMPLE VOLUME – only 20 µl sample / well
√ EASY – convenient ready to use protocol
√ MOST REFERENCED Sclerostin ELISA

Also available: Bioactive Sclerostin ELISA https://www.bmgrp.com/product/cardiovascular/biomedica-bioactive-sclerostin-elisa-human-sost/
√ specific antibodies targeting the receptor binging region

The only Sclerostin ELISA that utilizes specific EPITOPE MAPPED ANTIBODIES enabling the analysis of bioactive Sclerostin in clinical samples. 

Bioactive Sclerostin ELISA (cat.no. BI-20472) Assay Highlights:

• HIGHLY SPECIFIC and DEFINED: capture antibody directed against Sclerostin’s bioactive site. Learn more
• RELIABLE: human serum based calibrators and controls, rigorously validated
• LOW SAMPLE VOLUME: 20 µl / well
• QUICK: total incubation time 3.5 h

First bioactive Sclerostin ELISA for clinical samples

 

Areas of interest: osteoporosis, cancer induced bone diseases, rheumatoid arthritis, chronic inflammation, kidney diseases, therapy monitoring of anabolic treatment.

 

For detailed information please click corresponding links:

BI-20472 bioactive Sclerostin product website
BI-20472 bioactive Sclerostin ELISA IFU
BI-20472 bioactive Sclerostin ELISA Validation Data
BI-20472 bioactive Sclerostin ELISA MSDS

 

RELATED PUBLICATIONS

Circulating bioactive sclerostin levels in an Austrian population-based cohort. Kerschan-Schindl K, Föger-Samwald U, Gleiss A, Kudlacek S, Wallwitz J, Pietschmann P. Wien Klin Wochenschr. 2022 Jan;134(1-2):39-44. doi: 10.1007/s00508-021-01815-0. Epub 2021 Feb 5. PMID: 33544208; PMCID: PMC8813720.

Abstract

Sclerostin ELISA | BI-20492 Highlights:

• 
  The internationally most referenced human Sclerostin ELISA!
• 
  Rigorously validated according to FDA/ICH/EMEA guidelines
• 
  Low sample volume 
• New finding: Sclerostin in Alzheimer´s Disease

Bioactive Sclerostin ELISA Kit (Human SOST):

• 
  Specific antibodies targeting the receptor binding region
• 
  Rigorously validated for clinical samples according to FDA/ICH/EMEA guidelines
• 
  Low sample volume – 20 µl of serum/plasma per well 

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

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

FGF23 ELISA kits available for the US & CA

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

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

💡 What makes them a game-changer?

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

Biomedica offers world-leading quality products at competitive pricing.

FGF23 ELISA kits available for the US & CA

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

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

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

 

Literature

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

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

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

Kidney dysfunction causes disruptions in bone and mineral metabolism and changes in the regulators of the renal-bone axis through various mechanisms. Studies have demonstrated that fibroblast growth factor 23 (FGF23) and inflammatory markers rise, while iron status may decline (1, 2). In healthy individuals, FGF23 is regulated by phosphate, Vitamin D (1,25(OH)₂D), and parathyroid hormone (PTH). However in the early stages of chronic kidney disease (CKD), FGF23 levels begin to increase even before plasma phosphate levels increase (3).

Thus, CKD causes disruptions in bone and mineral metabolism that also includes the regulatory hormones, resulting chronic kidney disease-mineral bone disorder (CKD-MBD).

Bone biomarkers in early renal impairment

A recent study investigated the effects of Vitamin D supplementation in a cohort of healthy community-dwelling older people. Baseline blood concentrations of bone regulatory markers including Sclerostin (SOST), Dickkopf-related Protein 1 (DKK1); Osteoprotegerin (OPG) and soluble RANKL (sRANKL), Fibroblast growth factor 23 (intact and c-terminal FGF23) and TNF-alpha, Interleukin-6 (IL-6) were analysed. The results showed that SOST, cFGF23, iFGF23, PTH and TNF-alpha were elevated in the group of individuals with early kidney impairment compared to those with normal kidney function. Following Vitamin D supplementation, only cFGF23, 25(OH)D, and IL-6 showed differences between the groups.

The study identified alterations in the renal bone-axis that occur prior to clinical monitoring of patients. Early diagnosis in the initial stages of renal impairment may offer opportunities for preventing the progression of renal disease and chronic kidney disease-mineral bone disorder (CKD-MBD).

Learn more: Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation. Christodoulou M et al., Age Ageing. 2024; 53(5):afae096. doi: 10.1093/ageing/afae096. PMID: 38770543.

Bone biomarkers in early renal impairment

Biomedica offers quality ELISA Assay Kits for bone regulatory biomarkers

Sclerostin (SOST; cat.no. BI-20492)

Bioactive Sclerostin (bioSOST; cat. no. BI-20472)

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)

 

Key Features

• TRUSTED – cited in over 1000 publications
• Kit validations follows international quality guidelines
• Ready to use standards and controls included
• Developed & manufactured by Biomedica in Austria

 

Literature

1. Iron Deficiency Anemia in Chronic Kidney Disease. Gafter-Gvili A, Schechter A, Rozen-Zvi B. Acta Haematol. 2019;142(1):44-50. doi: 10.1159/000496492. Epub 2019 Apr 10. PMID: 30970355.
2. Iron-Deficiency Anemia in CKD: A Narrative Review for the Kidney Care Team. Hain D, Bednarski D, Cahill M, Dix A, Foote B, Haras MS, Pace R, Gutiérrez OM. Kidney Med. 2023 May 25;5(8):100677. doi: 10.1016/j.xkme.2023.100677. PMID: 37415621; PMCID: PMC10319843.
3. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Danziger J. Nephrol Dial Transplant. 2008 Sep;23(9):2733-7. doi: 10.1093/ndt/gfn260. Epub 2008 May 9. PMID: 18469306.

 

Join us at the ASBMR (American Society of Bone and Mineral Research) Conference at booth number 145. The annual meeting is taking place in Toronto, ON, Canada from September 27-30, 2024.

The American Society of Bone and Mineral Research (ASBMR) meeting is considered to be the largest event worldwide covering fields in bone, mineral and musculoskeletal research. The meeting attracts over 2,500 participants across the globe, including both clinicians and researchers working in different disciplines and at all career levels. The meeting provides attendees with exciting opportunities to exchange knowledge and to learn about the latest scientific and medical advances in the field.

Discover some of our biomarker assays for clinical research in bone and mineral disorders

–FGF23 intact and c-terminal

–Sclerostin and bioactive Sclerostin

–Osteoprotegerin(OPG)  and soluble RANKL

–Dickkopf-1 and Periostin

 

 

Exploring Biomarkers in Bone Biology

During the process of bone remodeling, bone cells release biomarkers that can aid in the evaluation of bone diseases and serve as valuable therapeutic targets. These bone biomarkers can be readily detected in serum and plasma samples using immunoassays.

A recent review by Nicolas H Hart et al., provides researchers and clinicians involved in bone and mineral metabolism with a comprehensive contemporary update on the Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskelet Neuronal Interact. 2020; ;20(3):347-371.

Abstract

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.

 

 

 

September is Blood Cancer Awareness Month raising awareness about the various types of blood cancers, including leukemia, lymphoma, myeloma, and other hematologic malignancies. The goal of this month-long initiative is to educate the public about the signs, symptoms, and the risks that are associated with these cancers, as well as the importance of early detection and treatment.

Some cancer treatments may lead to bone loss and increases the risk of osteoporosis and fractures. Learn more about the impact of intensive chemotherapy and glucocorticoid treatment on bone remodeling markers in children with acute lymphoblastic leukemia in the study described below (1).

The campaign also focuses on highlighting the latest advancements in blood cancer research and treatment, emphasizing that ongoing research is essential for improved outcomes and quality of life for patients.

September is Blood Cancer Awareness Month

Acute lymphoblastic leukemia (ALL) is a type of cancer that affects the blood and bone marrow. ALL is the most common cancer in children. Intensive chemotherapy has improved the 5-year survival rate for ALL patients up to 90%. However, this improved survival has resulted in long-term complications associated with chemotherapy, including negative effects on bone health including osteopenia/osteoporosis, osteonecrosis, and increased fragility fractures.

Skeletal health relies on a balance between bone resorption and bone formation

The health of the skeleton relies on a balance between bone resorption and bone formation, a process known as “bone remodeling,” which is regulated by the RANKL/RANK/osteoprotegerin (OPG) and Wnt/β-catenin signaling pathways.

Currently, there is a lack of data regarding the impact of intensive chemotherapy on bone remodeling markers in children with ALL. In a recent study, researchers in Italy investigated the role of bone remodeling markers in children with acute lymphoblastic leukemia after intensive chemotherapy and glucocorticoid (GC) treatment (1). The bone remodeling markers such as RANKL, OPG and the WNT signaling molecules Sclerostin and DKK-1 were also measured with ELISA kits from BIOMEDICA.

The researchers found “higher levels of RANKL and OPG in ALL children compared to the controls, with a balance of RANKL/OPG ratio, whereas the levels of sclerostin and DKK-1, the main inhibitors of osteoblastogenesis, were similar in the two groups of subjects. These results suggest that in our cohort of ALL subjects, the intensive chemotherapy and GCs increased osteoclastic activity and, thereby, bone resorption” (1).

About the RANK/RANKL/OPG system

The receptor-ligand duo, RANK and RANKL are crucial regulators of bone metabolism and osteoclast development. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL. It competitively binds to RANKL and interferes with the interaction of RANKL–RANK, thus blocking bone resorption. Beyond its role as a regulator of bone remodeling, the RANK/RANKL/OPG system has direct effects on the development of tumor cells, as it is implicated in the progression of breast and prostate cancer as well as leukemia.

About the WNT signaling molecules Sclerostin and DKK-1

Sclerostin (SOST) is mainly produced by osteocytes and is considered as the major regulator of bone formation. It is a soluble antagonist of the Wnt signaling pathway. Inactivating this pathway leads to bone degradation, while induction of Wnt signaling promotes bone formation.

Dickkopf-1 (DKK-1) is an extracellular protein. DKK-1 plays a role in the regulation of bone metabolism, and is a secreted inhibitor of the Wnt signaling pathway. DKK-1 inhibits the differentiation of osteoblasts and thereby bone formation. The dysregulation of DKK1 can lead to cancer progression.  

Biomedica offers quality kits for the measurement of these bone biomarkers

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

-Soluble free RANKL ELISA (cat. no. BI-20462)

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

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

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

 

• Widely cited in + 1000 publications
• Validated kits following international quality guidelines

 

Literature

1. Bone Remodeling Markers in Children with Acute Lymphoblastic Leukemia after Intensive Chemotherapy: The Screenshot of a Biochemical Signature. Muggeo P, Grassi M, D’Ascanio V, Brescia V, Fontana A, Piacente L, Di Serio F, Giordano P, Faienza MF, Santoro N. Cancers (Basel). 2023 Apr 29;15(9):2554. doi: 10.3390/cancers15092554. PMID: 37174020; PMCID: PMC10177249.
2. The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer. Medicina (Kaunas). De Leon-Oliva D, Barrena-Blázquez S, Jiménez-Álvarez L, Fraile-Martinez O, García-Montero C, López-González L, Torres-Carranza D, García-Puente LM, Carranza ST, Álvarez-Mon MÁ, Álvarez-Mon M, Diaz R, Ortega MA. 2023 Sep 30;59(10):1752. doi: 10.3390/medicina59101752. PMID: 37893470; PMCID: PMC10608105.
3. Understanding the Wnt Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Feasible Key against Relapses. Biology (Basel). Láinez-González D, Alonso-Aguado AB, Alonso-Dominguez JM. 2023 May 5;12(5):683. doi: 10.3390/biology12050683. PMID: 37237497; PMCID: PMC10215262.

We are present in over 60 countries, ensuring global availability and customer support through partnerships with selected local distributors on almost every continent. Regardless of your location, we are here to help you reach your goals.

With over 30 years of experience, we specialize in developing and manufacturing high-quality ELISA assay kits for biomarkers in clinical research.

Check out our ELISA Assay product brochure

Our ELISA Kits Travel Worldwide – contact us or your local representative 

About us

BIOMEDICA develops and manufactures high quality and widely cited immunoassays for clinical and pre-clinical applications in bone and cardiorenal diseases. For specific biomarkers, Biomedica has become a world-wide leader, e.g. Sclerostin, free sRANKL, OPG, DKK-1, and NT-proCNP.   

All Biomedica ELISA assays are fully validated following international quality guidelines. The assays include ready-to-use serum-based calibrators and controls enabling researchers to collect biologically reliable data.

This year’s ELISA assay highlights  

Cardiac Safety Biomarkers : Rat NT-proBNP, NT-proANP ELISA kits

FGF23  : FGF23 intact , FGF23 (C-terminal) ELISA kits

Cytokines  : VEGF, Angiopoietin-2, IL-6   

Discover our PROMOTION : Take 15% OFF of the human IL-6 ELISA Assay now through end of 2024! Making IL-6 ELISA Kits more affordable!

 

Features & Benefits of BIOMEDICA ELISA Assay Kits

• Highly Specific – many of our kits employ  characterized epitope-mapped antibodies
• Excellent Quality – our kits are validated according to international quality guidelines (ICH, FDA..)
• Convenient Use  –offering ready to use and color coded reagents – controls are included in all kits! 

 

Other Products

EZ4U – Cell Proliferation & Cytotoxicity Assay (cat. no. BI-5000) for reliable testing of cell viability in 96-well microtiter plates.

 Features & Benefits EZ4U Assay

-easy and convenient singe-step incubation for use on living cells

-non-radioactive

-cultivation can be continued after cell numbers are determined

-widely cited in more than 240 publications e.g.

• BRD4-targeting PROTACs Synergize With Chemotherapeutics Against Osteosarcoma Cell Lines
  Lang et al., Anticancer Res; 2024; 44 (3), 971-980.  PMID: 38423674
• Expression of cytokines in pleural effusions and corresponding cell lines of small cell lung cancer
  Rath et al., Transl Lung Cancer Res; 2024; 13 (1), 5-15. PMID: 38405004

July is acknowledged as Bone Cancer and Sarcoma Awareness Month, focusing on increasing awareness about rare and challenging cancers affecting children and adolescents. Sarcoma is a type of cancer that originates in the bones and soft tissues. Soft tissues include muscle, fat, blood vessels, fibrous tissues such as tendons and ligament. More than 70 different subtypes of sarcomas have been reported. However, all sarcomas can be divided into two main groups: soft tissue sarcomas and bone cancers.

Soft Tissue Sarcomas is a rare type of cancer that originates from the growth of cells within the body´s soft tissue. More than 50 different soft tissue sarcomas have been reported (3 ) Soft tissue sarcoma can occur anywhere in the body, but it most frequently develops in arms, legs, and abdomen (4).

Osteosarcoma is the most prevalent type of bone cancer in children and adolescents with and incidence of around 4.4. cases per million children reported each year (1). Genomic alterations, particularly the inactivation of TP53 and RB, are present in most cases of osteosarcoma.

Ewing sarcoma is the second most common bone tumor occurring most frequently in teenagers, with a median age of 15 years. Ewing sarcomas is an aggressive tumor that develops usually in bone, but sometimes in soft tissue, most commonly affecting the lower extremity and pelvis. At diagnosis, up to 25% of patients , commonly found in the lung, bones, and bone marrow (2). This condition is biologically driven by a chromosomal translocation, typically involving the EWS and FLI1 genes.

July is Sarcoma and Bone Cancer Awareness Month

• 5 Things to Know About Bone Cancer and Sarcoma Awareness Month- link

 

Wnt Signalling molecules Sclerostin (SOST) and Dickkopf-1 (DKK-1) in Sarcoma

 

SCLEROSTIN has been shown to be expressed in bone and cartilage forming skeletal tumors. Sclerostin is widely localized to areas in osteoblastic differentiation and ossification (5). In a study using an osteosarcoma mouse model, the administration of sclerostin resulted in inhibited tumor growth and extended survival periods (6).

DKK-1 is a wnt inhibitor that has been shown to partially improve osteosarcoma survival by upregulating aldehyde-dehydrogenase-1A1, neutralizing reactive oxygen species originating from nutritional stress and chemotherapeutic challenge (7). In a mouse model researches demonstrated the use of a DKK-1 targeting vivo morpholino that reduces tumour progression (7).

FGF23 in uterine sarcoma

Human FGF23 has been shown to be highly expressed in uterine sarcoma highlighting its potential as a biomarker for the diagnosis and prognosis of the disease (8).

Sclerostin, DKK-1 and FGF23 can easily be measured in blood, urine and cell culture supernatants with an ELISA assay.

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

– DKK-1 ELISA (cat. no. BI-20413)

– FGF23 ELISAs (cat. no. BI-20700, BI-20702)

Literature

1. Osteosarcoma. Pediatr Blood Cancer. Eaton BR, Schwarz R, Vatner R, Yeh B, Claude L, Indelicato DJ, Laack N. 2021 May;68 Suppl 2:e28352. doi: 10.1002/pbc.28352. Epub 2020 Aug 11. PMID: 32779875.
2. Ewing sarcoma. Pediatr Blood Cancer. Eaton BR, Claude L, Indelicato DJ, Vatner R, Yeh B, Schwarz R, Laack N. 2021 May;68 Suppl 2:e28355. doi: 10.1002/pbc.28355. PMID: 33818887.
3. More Than 50 Subtypes of Soft Tissue Sarcoma: Paving the Path for Histology-Driven Treatments. Katz D, Palmerini E, Pollack SM. Am Soc Clin Oncol Educ Book. 2018 May 23;38:925-938. doi: 10.1200/EDBK_205423. PMID: 30231352.
4. Malignant Soft-Tissue Sarcomas. Hematol Oncol Clin North Am. Brownstein JM, DeLaney TF. 2020 Feb;34(1):161-175. doi: 10.1016/j.hoc.2019.08.022. Epub 2019 Oct 28. PMID: 31739942.
5. Sclerostin expression in skeletal sarcomas. Shen J, Meyers CA, Shrestha S, Singh A, LaChaud G, Nguyen V, Asatrian G, Federman N, Bernthal N, Eilber FC, Dry SM, Ting K, Soo C, James AW. Hum Pathol. 2016 Dec;58:24-34. doi: 10.1016/j.humpath.2016.07.016. Epub 2016 Aug 3. PMID: 27498059; PMCID: PMC6560186.
6. Antitumor Effect of Sclerostin against Osteosarcoma. Ideta H, Yoshida K, Okamoto M, Sasaki J, Kito M, Aoki K, Yoshimura Y, Suzuki S, Tanaka A, Takazawa A, Haniu H, Uemura T, Takizawa T, Sobajima A, Kamanaka T, Takahashi J, Kato H, Saito N. Cancers (Basel). 2021 Nov 29;13(23):6015. doi: 10.3390/cancers13236015. PMID: 34885123; PMCID: PMC8656567.
7. Morpholino-driven blockade of Dkk-1 in osteosarcoma inhibits bone damage and tumour expansion by multiple mechanisms. Pan S, Cesarek M, Godoy C, Co CM, Schindler C, Padilla K, Haskell A, Barreda H, Story C, Poole R, Dabney A, Gregory CA. Br J Cancer. 2022 Jul;127(1):43-55. doi: 10.1038/s41416-022-01764-z. Epub 2022 Mar 11. PMID: 35277659; PMCID: PMC9276700.
8. Fibroblast Growth Factor 23 is a Potential Prognostic Biomarker in Uterine Sarcoma. Yang L, Cai Y, Wang Y, Huang Y, Zhang C, Ma H, Zhou JG. Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241245924. doi: 10.1177/15330338241245924. PMID: 38613349; PMCID: PMC11015760.

We are excited to be soon exhibiting at the International Conference on Children’s Bone Health (ICCBH) in Salzburg, Austria from June 22-25, 2024.

Join us at booth number 4 and explore our widely trusted Biomarker ELISA Assay Kits including Fibroblast Growth Factor (FGF23), Sclerostin, Periostin, NT-proCNP, and many others.

We look forward to connecting with you!

Join us at the International Conference on Children’s Bone Health

Click here for more information about the conference for anyone who is interested in 

bone metabolism and bone mass in children, adolescents and young adults.

The ICCBH conference aims to unite researchers, clinicians, health professionals, and others from different fields to gain an understanding of the developing skeleton with regards to childhood health and disease. Latest advancements, innovative therapies, and genetic discoveries will be discussed.

More about Biomarkers in Bone Biology  

Bone cells release biomarkers during bone remodeling. They can be used in assessing bone diseases and represent useful therapeutic targets. Bone biomarkers can easily be detected in serum and plasma samples by immunoassay.  

A recent review by Ponds-Belda OD et al., Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23 focuses on various aspects of FGF23 metabolism in children, reference values,  and other key variables involved in mineral homeostasis. 

BIOMEDICA offers quality kits to measure various bone biomarkers 

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

Machine Learning for Bone Biomarker Profiling in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder which can lead to severe joint damage and disability. In 2019, an estimated 18 million people worldwide were living with this disease (1). Untreated RA can lead to destruction of the joints as well as heart, lung or nervous system problems (2). Skeletal bone loss, referred to as osteopenia or osteoporosis, is a key feature of RA. 

Sclerostin and Dickkopf-1 (DKK-1) are Wnt signaling proteins that are secreted by osteocytes, bone cells embedded in the bone matrix. They are inhibitors of bone formation and play a key role in the pathogeneses of systemic and localized bone loss in RA (3, 4). Serum levels of Sclerostin and DKK-1 have shown to be elevated in patients with RA compared to controls and correlate with bone erosions and inflammation (4, 5, 6). Findings in mice have demonstrated that DKK-1 triggers inflammatory bone degradation and neutralization of DKK-1 protects from systemic bone loss during inflammation (7). Interestingly, blocking the bone destruction molecule Sclerostin with an anti-sclerostin antibody has shown to be effective for the treatment of osteoporosis but may not be safe for patients suffering from inflammatory RA: in a rodent RA model, Weymeyer et al. demonstrated that Sclerostin inhibition did not stop bone loss and worsened clinical RA outcome by promoting TNF-dependent inflammatory joint destruction (8).

Controlling inflammation by biological therapies targeting pro-inflammatory cytokines has shown to have a positive effect in RA patients (5). Interleukin-6 is a key immunomodulatory cytokine that plays an important role in the development of RA. Inhibition of IL-6 has proven to be effective in treating patients with RA (9). A study by Briot et al showed that DKK-1 levels decreased in RA patients treated with an anti-IL-6 inhibitor (6).

Machine Learning for Bone Biomarker Profiling in Rheumatoid Arthritis

A recent cross-sectional study by Adami G et al., with over 1800 enrolled participants diagnosed with RA, Psoriatic Arthritis (PsA), and Systemic Sclerosis (SSc), employed machine learning techniques to assess the capability of biomarker profiles in differentiating RA patients from individuals with PsA and SSc. The Wnt signaling antagonists Sclerostin and Dickkopf-1 (DKK-1) were among the biomarkers measured. The study provided an in-depth understanding into the bone signature of RA that is marked by changes in bone mineral density and by unique biomarker profiles (6). Serum Sclerostin and DKK-1 levels were measured with ELISA assay kits from Biomedica.

SCLEROSTIN ELISA (#BI-20492) and DKK-1 (#BI-20403) ELISA kits

Biomedica´s Sclerostin ELISA Assay

• TRUSTED – cited in more than 290 publications!
• QUALITY – validated according to international guidelines
• EFFICIENT – only 20µl sample / well
• CONVENIENT – ready to use standards and controls included

 

Biomedica´s DKK-1 ELISA assay 

• TRUSTED – cited in more than 180 publications!
• QUALITY – validated according to international guidelines
• EFFICIENT – only 20µl sample / well
• CONVENIENT – direct measurement – no sample pre-dilution. Ready to use standards and controls included

 

Also available from Biomedica : Bioactive Sclerostin ELISA (cat. no. BI-20472), Interleukin-6 ELISA (BI-IL6)

 

Complete ready-to use ELISA kits

 

Literature

1. GBD 2019: Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. https://vizhub.healthdata.org/gbd-results
2. WHO- Rheumatoid arthritis, June 2023
3. Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis. Cici D, Corrado A, Rotondo C, Cantatore FP. Int J Mol Sci. 2019 Nov 7;20(22):5552. doi: 10.3390/ijms20225552. PMID: 31703281; PMCID: PMC6888549.
4. Study of correlation of level of expression of Wnt signaling pathway inhibitors sclerostin and dickkopf-1 with disease activity and severity in rheumatoid arthritis patients. Singh A, Gupta MK, Mishra SP.Drug Discov Ther. 2019;13(1):22-27. doi: 10.5582/ddt.2019.01011. PMID: 30880318.
5. The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis. Briot K, Rouanet S, Schaeverbeke T, Etchepare F, Gaudin P, Perdriger A, Vray M, Steinberg G, Roux C. Joint Bone Spine. 2015 Mar;82(2):109-15. doi: 10.1016/j.jbspin.2014.10.015. Epub 2014 Dec 31. PMID: 25557658.
6. Machine learning to characterize bone biomarkers profile in rheumatoid arthritis. Adami G, Fassio A, Rossini M, Benini C, Bixio R, Rotta D, Viapiana O, Gatti D. Front Immunol. 2023 Nov 9;14:1291727. doi: 10.3389/fimmu.2023.1291727. PMID: 38022514; PMCID: PMC10665911.
7. Neutralisation of Dkk-1 protects from systemic bone loss during inflammation and reduces sclerostin expression. Heiland GR, Zwerina K, Baum W, Kireva T, Distler JH, Grisanti M, Asuncion F, Li X, Ominsky M, Richards W, Schett G, Zwerina J. Ann Rheum Dis. 2010 Dec;69(12):2152-9. doi: 10.1136/ard.2010.132852. Epub 2010 Sep 21. PMID: 20858621.
8. Sclerostin inhibition promotes TNF-dependent inflammatory joint destruction. Wehmeyer C, Frank S, Beckmann D, Böttcher M, Cromme C, König U, Fennen M, Held A, Paruzel P, Hartmann C, Stratis A, Korb-Pap A, Kamradt T, Kramer I, van den Berg W, Kneissel M, Pap T, Dankbar B. Sci Transl Med. 2016 Mar 16;8(330):330ra35. doi: 10.1126/scitranslmed.aac4351. Epub 2016 Mar 16. PMID: 27089204.
9. Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned? Avci AB, Feist E, Burmester GR. BioDrugs. 2024 Jan;38(1):61-71. doi: 10.1007/s40259-023-00634-1. Epub 2023 Nov 21. PMID: 37989892; PMCID: PMC10789669.

 

Kidney disease is estimated to affect more than 800 million people worldwide (1). Taking action for prevention, early diagnosis and treatment can reduce the risk and the burden of kidney disease.

Role of the kidneys, kidney disease and risk factors

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 (2), whereas acute kidney disease – acute kidney injury (AKI) is characterized by a sudden loss of excretory kidney function (3).

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). GN is a group of diseases characterized by inflammation of the glomeruli, the filtration units of the kidney (4).

The most common risk factors for the development and progression of CKD are diabetes and high blood pressure. Managing blood sugar and blood pressure can help keep kidneys healthy. Other risk factors of CKD include heart disease, obesity, family history and genetic background as well as age, smoking and nutrition (5).

Consequences of kidney disease include heart disease, high blood pressure, bone and mineral disorders, and anemia (6).

Keep Your Kidneys Healthy

Regular exercise, weight control, a balanced diet (7) and sufficient fluid intake are only some of the ways to keep your kidney healthy.

World Kidney Day – about kidney health download here and check out the 6-Step Guide to Protecting Kidney Health here .

BIOMEDICA – Biomarker ELISA kits for clinical research in kidney disease

• HIGH QUALITY ASSAYS – Fully validated according to international quality guidelines
• TRUSTED – Widely cited in over 1500 publications

 

ELISA kits for: FGF23 (Fibroblast growth factor 23), Vanin-1, Endostatin, Sclerostin, Osteoprotegerin (OPG), Angiopoietin-2 (ANG-2), IL-6 (Interleukin-6) , VEGF (Vascular Endothelial Growth Factor)

Check out our brochure on Biomarkers in Clinical Nephrology  

 

 

Literature

1. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). Kovesdy CP. 2022 Apr;12(1):7-11. doi: 10.1016/j.kisu.2021.11.003. Epub 2022 Mar 18. PMID: 35529086; PMCID: PMC9073222.
2. 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.
3. Acute kidney injury. Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Nat Rev Dis Primers. 2021 Jul 15;7(1):52. doi: 10.1038/s41572-021-00284-z. PMID: 34267223.
4. Glomerulonephritis: immunopathogenesis and immunotherapy. Anders HJ, Kitching AR, Leung N, Romagnani P.Nat Rev Immunol. 2023 Jul;23(7):453-471. doi: 10.1038/s41577-022-00816-y. Epub 2023 Jan 12. PMID: 36635359; PMCID: PMC9838307.
5. Risk factors for chronic kidney disease: an update. Kazancioğlu R Kidney Int Suppl (2011). 2013 Dec;3(4):368-371. doi: 10.1038/kisup.2013.79. PMID: 25019021; PMCID: PMC4089662.
6. Cardiorenal Syndrome and the Role of the Bone-Mineral Axis and Anemia. Charytan DM, Fishbane S, Malyszko J, McCullough PA, Goldsmith D Am J Kidney Dis. 2015 Aug;66(2):196-205. doi: 10.1053/j.ajkd.2014.12.016. Epub 2015 Feb 26. PMID: 25727384; PMCID: PMC4516683.
7. The Effect of Diet on the Survival of Patients with Chronic Kidney Disease. Rysz J, Franczyk B, Ciałkowska-Rysz A, Gluba-Brzózka A.Nutrients. 2017 May 13;9(5):495. doi: 10.3390/nu9050495. PMID: 28505087; PMCID: PMC5452225.

 

 

 

Rare Disease Day is a global initiative held on the last day of February. It raises awareness for rare diseases to improve accessibility to medical treatment and representation for individuals diagnosed with rare diseases. It is estimated that around 300 million people worldwide are living with rare diseases.

Rare metabolic bone diseases are caused by genetic disorders that may directly or indirectly have an impact on bone structure or function (1). Other factors like hormones, tumors, diet or certain medications may also lead to abnormal growth and development of the skeleton. Some of the diseases are inherited many caused by genetic mutations. Other bone disorders are not inherited and can develop after birth.In some cases, the precise cause remains unknown.

Rare bone diseases

Rare bone diseases account for 5% of all birth defects and are an important cause of disability worldwide, yet they remain a difficult group of conditions to treat (2). It is estimated that more than 400 developmental abnormalties of the skeletal system exist (3).

The main rare metabolic bone diseases include Hypophosphatemia, Osteogenesis Imperfecta, Tumor-Induced Osteomalacia, X-Linked Hypophashatemia, and other Rare Bone Diseases (Fibrous Dysplasia, Osteopetrosis, High Bone Mass..) (4).

Biomarkers in Rare Bone Diseases

Biomarkers in Rare Bone Diseases provide a way to accelerate medical research by providing valuable insights into disease mechanisms. They play an important role in monitoring disease progression, optimizing treatments. and developing novel therapies.

NT-proCNP  

C-natriuretic peptide (CNP) and its receptor, natriuretic peptide receptor-B (NPR-B) are important regulators of endochondral ossification and longitudinal bone growth (5, 6)  The discovery and understanding of their physiological functions in promoting longitudinal bone growth have created opportunities for a specific targeted strategy in achondroplasia, the most common form of human dwarfism (7).

RANKL and OPG

Receptor activator of nuclear factor (NF-kappaβ) ligand (RANKL), its cellular receptor, receptor activator of NF-kappaβ (RANK), and the decoy receptor osteoprotegerin (OPG) are part of a cytokine system that regulate bone formation and resorption (8) . Denosumab is a bone anti-resorptive drug, a monoclonal antibody that binds RANKL and disrupts bone resorption. It has been approved for the treatment of osteoporosis and other bone-related disorders. The use of Denosumab in pediatric patients with Osteogenesis Imperfecta (OI), a genetic bone disorder, also known as brittle bone disease, shows decreased fractures and improved bone growth (9). A clinical trial at the National Institutes of Health found that Denosumab, significantly reduced abnormal bone turnover in adults with fibrous dysplasia, a rare disease characterized by weak, oddly shaped, or broke bones.

SCLEROSTIN

Sclerostin is a secreted protein that decreases bone formation. It binds to LRP-5 receptor on the surface of osteoblasts and consequently interferes with WNT signalling. Genetic sclerostin deficiency leads to increased bone formation and sclerotic bone disorders. Sclerostin inhibition is being evaluated as a potential approach to increase bone mass in Osteogenesis Imperfecta (10).

FGF23

Fibroblast growth factor 23 (FGF23) is a hormone that is produced by bone. It regulates serum phosphate levels by suppressing phosphate reabsorption in the kidney. Excessive actions of FGF23 are responsible for different kinds of hypophosphatemic rickets as found in X-linked hypophosphatemia (XLH) and osteomalacia. XLH is characterized by deformities of the lower limb and short stature. An anti-fibroblast growth factor-23 (FGF23) monoclonal antibody (Burosumab) has been approved as a novel treatment for hypophopshatemic rickets (11).

Measurement of FGF23 is a critical tool to assist in the evaluation and diagnosis of hypophosphatemic conditions (12, 13).

The second most common genetic form of hypophosphatemic rickets after XLH, is autosomal-dominant hypophosphatemic rickets (ADHR). ADHR is caused by specific mutations in the FGF23 gene.

FGF23 can reliably be measured with an immunoassay (14).

FGF23 ELISAs (c-term FGF23, cat. no BI-20702) (intact FGF23, cat. no. BI-20700)

• MULTI-USE for serum and plasma samples
• TRUSTED in over 60 citations

 

FGF23 – Test

 

Biomarker ELISA assay kits from BIOMEDICA

Complete ready-to use ELISA kits 

 

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

• CONVENIENT – low sample volume – 20 µl / well
• RELIABLE – validated following international quality guidelines
• TRUSTED – widely cited in over 40 publications (click here for full list)
• MULTI-USE – for human serum and plasma samples; protocols for non-human samples (e.g. rat). 

 

Citations Selection of NT-proCNP ELISA citations related to skeletal disorders:

• Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth. Espiner E et al.,Horm Res Paediatr. 2018. 90(6):345-357. doi: 10.1159/000496544. PMID: 30844819.
• Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death. Fujii T et al., PLoS One. 2018. 22;13(3):e0194812. doi: 10.1371/journal.pone.0194812. PMID: 29566041.
• Serum NT-proCNP levels increased after initiation of GH treatment in patients with achondroplasia/hypochondroplasia. Kubota T etal., Clin Endocrinol (Oxf). 2016 Jun;84(6):845-50. doi: 10.1111/cen.13025. Epub 2016 Feb 25. PMID: 26814021.
• Acromesomelic dysplasia, type maroteaux caused by novel loss-of-function mutations of the NPR2 gene: Three case reports. Wang W et al., 2016. Am J Med Genet A 170A, 426–434.
• Skeletal overgrowth syndrome caused by overexpression of C-type natriuretic peptide in a girl with balanced chromosomal translocation, t(1;2)(q41;q37.1). Ko J et al., 2015. Am J Med Genet A 167A, 1033–1038. 

 

RANKL ELISA (cat. no. BI-20462)

• Highly sensitive – measurable concentrations in healthy subjects
• Only assay that measures free, uncomplexed, soluble RANK Ligand
• TRUSTED in over 300 citations 

 

OPG ELISA (BI-20403)

• CONVENIENT- ready to use liquid calibrators and controls
• EFFICIENT – low sample volume 20µl / well
• TRUSTED in over 250 citations 

 

Literature 

1. Genetic approaches to metabolic bone diseases. Hannan FM, Newey PJ, Whyte MP, Thakker RV. Br J Clin Pharmacol. 2019. 85(6):1147-1160. doi: 10.1111/bcp.13803. PMID: 30357886; PMCID: PMC6533455.
2. The evolving therapeutic landscape of genetic skeletal disorders. Sabir, A.H., Cole, T. Orphanet J Rare Dis 14, 300 (2019).
3. Changes in skeletal dysplasia nosology. Jurcă MC, Jurcă SI, Mirodot F, Bercea B, Severin EM, Bembea M, Jurcă AD. Rom J Morphol Embryol. 2021. 2(3):689-696. doi: 10.47162/RJME.62.3.05. PMID: 35263396; PMCID: PMC9019670.
4. Atlas of rare genetic metabolic bone diseases. IOF, 2024.
5. Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway. Yasoda A, Ogawa Y, Suda M, Tamura N, Mori K, Sakuma Y, Chusho H, Shiota K, Tanaka K, Nakao K J Biol Chem.1998. 8;273(19):11695-700. doi: 10.1074/jbc.273.19.11695. PMID: 9565590.
6. Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. Miyazawa T, Ogawa Y, Chusho H, Yasoda A, Tamura N, Komatsu Y, Pfeifer A, Hofmann F, Nakao K. Endocrinology. 2002. 143(9):3604-10. doi: 10.1210/en.2002-220307. PMID: 12193576.
7. Optimal management of complications associated with achondroplasia. Ireland PJ, Pacey V, Zankl A, Edwards P, Johnston LM, Savarirayan R Appl Clin Genet. 2014. 7:117-25. doi: 10.2147/TACG.S51485. PMID: 25053890; PMCID: PMC4104450.
8. C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and -independent pathways. Agoston H, Khan S, James CG, Gillespie JR, Serra R, Stanton LA, Beier F BMC Dev Biol. 2007. 7:18. doi: 10.1186/1471-213X-7-18. PMID: 17374144; PMCID: PMC1847438.
9. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. Hofbauer LC, Heufelder AE. J Mol Med (Berl). 2001 Jun;79(5-6):243-53. doi: 10.1007/s001090100226. PMID: 11485016.
10. Effect of denosumab on the growing skeleton in osteogenesis imperfecta. Hoyer-Kuhn H, Semler O, Schoenau E.J Clin Endocrinol Metab. 2014. 99(11):3954-5. doi: 10.1210/jc.2014-3072. PMID: 25148238.
11. Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta. Marulanda J, Tauer JT, Boraschi-Diaz I, Bardai G, Rauch F. Sci Rep. 2023. 13(1):5010. doi: 10.1038/s41598-023-32221-3. PMID: 36973504; PMCID: PMC10043013.
12. Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management. Charoenngam N, Nasr A, Shirvani A, Holick MF.Genes (Basel). 2022. 13(10):1880. doi: 10.3390/genes13101880. PMID: 36292765; PMCID: PMC9601711.
13. Determination of FGF23 Levels for the Diagnosis of FGF23-Mediated Hypophosphatemia. Hartley IR, Gafni RI, Roszko KL, Brown SM, de Castro LF, Saikali A, Ferreira CR, Gahl WA, Pacak K, Blau JE, Boyce AM, Salusky IB, Collins MT, Florenzano P. J Bone Miner Res. 2022. 37(11):2174-2185. doi: 10.1002/jbmr.4702. PMID: 36093861; PMCID: PMC9712269.
14. The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Heijboer AC, Cavalier E Calcif Tissue Int. 2023. 112(2):258-270. doi: 10.1007/s00223-022-00987-9. PMID: 35665817; PMCID: PMC9859838.

 

 

 

The enzyme-linked immunosorbent assay (ELISA or EIA) is a laboratory method to detect and quantify the presence of a protein in biological samples (1, 2).

When selecting an ELISA kit, researchers are often confronted with the question which assay to choose of the many commercially available kits.

It can be a challenge! Here are a few hints that may help.

HOW TO CHOOSE THE RIGHT ELISA KIT

As a general rule, before purchasing an assay, always read the protocol booklet (instructions for use – IFU or package insert) in detail. This should ensure that the kit will be suitable for your requirements. Check out the following:

1. ANALYTE

Which protein biomarker will you be measuring? Be sure to use the correct term during your search. Some biomarkers have alternative names (e.g. Sclerostin or SOST ELISA (SOST is actually the name for the gene that encodes Sclerostin).

2. SPECIES – SPECIFICITY – CROSS REACTIVITY

Verify if the assay can be used in the respective model such as e.g. human, rat, or mouse. Due to high homology between species, some ELISA kits work both in humans and in different animal species. As an example the biomarker ELISA kit for NT-proANP was developed for human use but 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

What is the sample type (matrix) you´ll be using (e.g. serum, EDTA-plasma, heparin-plasma, citrate-plasma, cell culture supernatants, urine..) ?

Verify if the assay is compatible for your sample type: check the package insert and, if available, check if there are validation data showing results (often found on the manufacturers website).

Of note: analysis of some biomarkers in the “wrong” matrix can lead to “false” results due to a matrix effect.

4. SAMPLE VOLUME

Check the amount of sample required per well (calculate volume to measure your samples in duplicates). Low sample volumes and precious samples are often a selection criterium.  

5. SENSITIVTY – BIOMARKER CONCENTRATIONS TO BE EXPECTED

Before choosing an assay, look into the validation data of the kit (often documented in the ELISA protocol booklet or in the validation data files).  

Reference values and pathological values in serum and/or plasma of the biomarker of interest are sometimes documented as well. These data can be helpful in selecting an appropriate assay. In some cases samples may require a pre-dilution. Therefore, always verify if the dilution buffer (assay buffer) is included in the kit or ask the assay developer for their input.

Of note: assays offering high sensitivity offer a different dynamic range than assays with a lower sensitivity. The dynamic range of an assay indicates the range of concentrations over which an assay can accurately quantify the analyte.

6. ASSAY PERFORMANCE – ASSAY VALIDATION

Careful evaluation of the assay´s performance characteristics is important in selecting an ELISA kit.

Choose an assay that has gone through a rigorous validation process. Check out if you can find data on the following performance characteristics:

• Accuracy- detection of a protein biomarker in clinical samples.
• Dilution linearity and parallelism  – recovery of the analyte of interest in diluted samples
• Specificity & cross-reactivity – making sure that you detect only the analyte of interest
• Precision – within-run and in-between run precision – ensuring precise and reproducible results within an across assay lots
• 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..).

 

7. KIT COMPONENTS

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

8. CITATIONS & REFERENCES

Check if there are citations on the manufacturers website for the specific ELISA kit. Look into publications and seek feedback from researchers who have used the assay you are considering.

9. PRODUCT ORIGIN

Verify if the kit supplier is the kit manufacturer. More and more kits are repacked and are sold under different names, although it is always the same kit.

ELISA kit manufacturers 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..).

10. CUSTOMER SUPPORT

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

 

Related Literature

1.Enzyme-Linked Immunosorbent Assay: Types and Applications. Hayrapetyan H, Tran T, Tellez-Corrales E, Madiraju C. Methods Mol Biol. 2023;2612:1-17. doi: 10.1007/978-1-0716-2903-1_1. PMID: 36795355.

2. Enzyme Immunoassay (EIA)/Enzyme-Linked Immunosorbent Assay (ELISA). Lequin RM, Clinical Chemistry. 2005; 51, 12:  2415-2418.

 

Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disease that leads to progressive muscle fiber degeneration and weakness. There is no cure for this disease and current therapy consists on treatment with glycocorticoids (GC). GC therapy is linked to risk of bone loss and increased fracture risk. Despite their adverse effects GC remain the standard care to slow down disease progression (2).

Steroid therapy and fracture prevention in Duchenne Muscular Dystrophy

This recent study explored factors that are associated with incident fracture risk in glucocorticoid (GC)-treated patients with Duchenne muscular dystrophy (DMD): Risk Factors Associated with Incident Vertebral Fractures in Steroid-treated Males with Duchenne Muscular Dystrophy. Brief, vertical fractures (VF) were prospectively evaluated in 38 males with Duchenne muscular dystrophy at study baseline and 12 months . The authors concluded the following: ” The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.”

Steroid therapy and fracture prevention in Duchenne Muscular Dystrophy – The Biomedica IL-6 and Sclerostin ELISA were highlighted in this study.

High Sensitivity IL-6 ELISA  (cat. no. BI-IL6) – measurable values in serum and plasma samples.

• Format: 12×8 wells
• Sensitivity: 0.28 pg/ml
• Dynamic Range: 0-200 pg/ml
• Assay Time: 4 hours 30 minutes
• Sample Type: Serum, Plasma, Cell Culture Supernatants, Urine
• Sample Volume: 100 µl
• Alternative Name: Interleukin 6
• Kit includes 7 pre-diluted calibrators and 2 controls

 

Sclerostin ELISA (cat. no. BI-20492) 

• Format: 12×8 wells
• Sensitivity: 3.2 pmol/l (= 72 pg/ml)
• Dynamic Range: 0 to 240 pmol/l (=0-5400 pg/ml)
• Assay Time: 18-25h (overnight incubation) / 1 h /30 min
• Sample Type: Serum, Plasma, Cell Culture Supernatants, Urine
• Sample Volume: 20 µl
• Alternative Name: SOST
• Kit includes 6 pre-diluted calibrators and 1 control

 

Are you planning a study? Contact us to learn about our promotions info@bmgrp.com

Literature

1.Risk Factors Associated with Incident Vertebral Fractures in Steroid-treated Males with Duchenne Muscular Dystrophy. Phung K, McAdam L, Ma J, McMillan HJ, Jackowski S, Scharke M, Matzinger MA, Shenouda N, Koujok K, Jaremko JL, Wilson N, Walker S, Hartigan C, Khan N, Page M, Robinson ME, Saleh DS, Smit K, Rauch F, Siminoski K, Ward LM.J Clin Endocrinol Metab. 2023 Aug 23:dgad435. doi: 10.1210/clinem/dgad435. Epub ahead of print. PMID: 37610420.

Abstract

Purpose: Prevention of fractures is an unmet need in glucocorticoid (GC)-treated Duchenne muscular dystrophy. This study explored factors associated with incident vertebral fractures (VFs) to inform future fracture prevention efforts. Methods: VFs were evaluated prospectively at study baseline and 12 months on lateral spine radiographs in participants aged 4 to 25 years with Duchenne muscular dystrophy. Clinical factors were analyzed for their association with the change in Spinal Deformity Index (sum of the Genant-defined VF grades from T4 to L4) between baseline and 12 months. Results: Thirty-eight males were evaluated (mean ± SD age at baseline 11.0 ± 3.6 years; mean ± SD GC duration at baseline 4.1 ± 3.1 years; 74% ambulatory). Nine of 38 participants (24%) had 17 incident VFs, of which 3/17 VFs (18%) were moderate/severe. Participants with 12-month incident VF had lower mean ± SD baseline lumbar spine areal bone mineral density Z-scores (-2.9 ± 1.0 vs -1.9 ± 1.1; P = .049) and lower total body less head areal bone mineral density Z-scores (-3.1 ± 1.2 vs -1.6 ± 1.7; P = .036). Multivariable linear regression showed that at least 1 VF at baseline (P < .001), a higher number of antecedent non-VF (P < .001), and greater bone age delay at baseline (P = .027) were significant predictors of an increase in the Spinal Deformity Index from baseline to 12 months. Conclusion: The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.

2. Emerging therapies for Duchenne muscular dystrophy. Markati T, Oskoui M, Farrar MA, Duong T, Goemans N, Servais L. Lancet Neurol. 2022 Sep;21(9):814-829. doi: 10.1016/S1474-4422(22)00125-9. Epub 2022 Jul 15. PMID: 35850122.

 

 

 

Bone Health & Osteoporosis – Biomarkers of Bone Regulation

Maintaining strong and healthy bones is essential for our well-being. Bone not only provides structural support for the body but also protects vital organs and serves as a provider for minerals such as calcium and phosphorus. Bone density and bone strength are key components of bone health.

Osteoporosis is a condition of weakened and fragile bones. It is the most common metabolic bone disease in the world (1) that can affect individuals of various ages, but is more commonly associated with aging. Both men and women can be affected, but postmenopausal women are at higher risk to develop Osteoporosis due to the decline of hormonal estrogen levels which plays a protective role in bone. Prevention of Osteoporosis includes a balanced diet and exercise.

Bone remodeling is a continuous process that is tightly regulated between bone resorption of old or damaged bone and the formation of new bone. Various hormones and factors are involved in bone metabolism. The bone cycle consists of different phases and markers of bone metabolism can be categorized as markers of bone formation, markers of bone resorption and markers of the regulation of  bone metabolism.

Bone Health & Osteoporosis – biomarkers of bone regulation

Protein biomarkers are often used in clinical research or clinical settings to assess bone health and to monitor the effectiveness of Osteoporosis treatments. Some of these biomarkers provide information about the regulatory processes involved in bone metabolism and turnover.

Monitoring these biomarkers can provide information on the overall health of bones. Some of these regulatory biomarkers include:

• Sclerostin (SOST) – is produced by osteocytes, bone cells embedded in the bone. Sclerostin is a bone specific Wnt pathway inhibitor, that negatively regulates bone formation, by promoting osteoclastogenesis and bone resorption (3). Elevated Sclerostin levels may indicate decreased bone formation.

 

• Dickkopf-1 (DKK-1) – is like Sclerostin an inhibitor of Wnt signaling, which is crucial for bone formation. Elevated serum DKK-1 promote bone resorption (4). DKK-1 levels may indicated suppressed bone formation.

 

• Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL) – is a key regulator of osteoclast activation and formation. RANKL promotes bone resorption by activating the bone osteoclasts. RANKL is secreted by osteocytes and is the most important factor of osteoclast formation (5).  

 

• Osteoprotegerin (OPG) – is the decoy receptor for RANKL. OPG regulates bone resorption (6). Changes in the OPG / RANKL ratio can affect bone remodeling.

 

• Fibroblast growth factor (FGF23) – is a hormone that regulates phosphate homeostasis and vitamin D metabolism. Abnormal FGF23 levels are associated with disorders affecting bone health e.g. hypophosphatemic rickets (7). 

   

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

   

  BIOMEDICA´s Bone Marker ELISA kits

  

• Sclerostin (SOST) ELISA  (BI-20492)

  • Most referenced Sclerostin ELISA +290 citations
  • Low sample volume – 20µl / well
  • Validation following international guidelines

   

• Bioactive Sclerostin ELISA (BI-20472)

  • Targets the receptor binding region
  • Rigorously validated for clinical samples according to FDA/ICH/EMEA guidelines
  • Low sample volume – 20 µl of serum/plasma per well 

   

• Dickkopf-1 (DKK-1) ELISA  (BI-20413)

  • Widely cited +170 publications
  • Direct measurement
  • Validated following international guidelines

   

• Osteoprotegerin (OPG) ELISA (BI-20403)

  • most referenced human OPG ELISA in +250 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 ELISA that measures free, uncomplexed soluble RANKL
  • Cited in over +300 citations 

   

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

  • for serum and plasma samples
  • full validation 
  • cited in +50 publications

   

• FGF23 intact ELISA (BI-20700)

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

  

  Literature

  1. The clinician’s guide to prevention and treatment of osteoporosis. LeBoff MS et al., Osteoporos Int. 2022 Oct;33(10):2049-2102. doi: 10.1007/s00198-021-05900-y.
  2. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F et al., Osteoporos Int. 2023 Feb;34(2):213-238. doi: 10.1007/s00198-022-06523-7.
  3. Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments. Maeda K et al., Int J Mol Sci. 2022 Mar 6;23(5):2871. doi: 10.3390/ijms23052871.
  4. Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption. Kitaura H et al., Int J Mol Sci. 2020 Jul 21;21(14):5169. doi: 10.3390/ijms21145169.
  5. The Role of Osteoprotegerin in Vascular Calcification and Bone Metabolism: The Basis for Developing New Therapeutics. Rochette L et al., Calcif Tissue Int. 2019 Sep;105(3):239-251. doi: 10.1007/s00223-019-00573-6.
  6. FGF23-related hypophosphatemic rickets/osteomalacia: diagnosis and new treatment. Fukumoto S. J Mol Endocrinol. 2021 Feb;66(2):R57-R65. doi: 10.1530/JME-20-0089.

   

 

With advancing age, the human body´s natural capacity to consistently renew bones and maintain their resilience diminishes. This decline is enhanced by conditions like osteoporosis. This poses a significant health concern for the elderly and is becoming a growing economic challenge on society. In an effort to address this problem, scientists are actively seeking novel therapeutic strategies to enhance bone regeneration.

 

Building bone with bioinspired molecules

By employing computer models and simulations, a Dresden-based team created innovative bio-inspired compounds that enhance bone regeneration in mice. These compounds can be incorporated into biomaterials, allowing for their localized introduction into bone defects. These newly developed molecules derive from glycosaminoglycans, which are extended sugar chains like hyaluronic acid or heparin. These molecules could be used to turn-off proteins like DKK-1 and Sclerostin that block bone regeneration that could lead to new and more effective therapies for bone diseases.

DKK-1 and SCLEROSTIN are two important proteins that play significant roles in regulating bone health and development.

DKK-1 (Dickkopf-1) acts as an inhibitor of the Wnt signaling pathway. This pathway is crucial for bone formation. Overexpression of DKK-1 leads to a decrease in bone formation characterized by conditions with impaired bone density and increased fragility, such as osteoporosis.

SCLEROSTIN (SOST) is a Wnt signaling inhibitor and a negative regulator of bone formation. Sclerostin is primarily produced by osteocytes, which are bone cells embedded within the bone matrix.

Sclerostin and DKK-1 can be measured in human serum samples with an ELISA assay.

 

Biomedica´s DKK-1 ELISA assay (cat. no. BI-20413)

• 20µl sample volume
• Widely cited
• No sample dilution
• Fully validated

 

Biomedica´s Sclerostin ELISA assay (cat. no. 20492)

• The internationally most referenced Sclerostin ELISA!
• Rigorously validated according to FDA/ICH/EMEA guidelines
• 20µl sample volume

 

also available: Bioactive Sclerostin ELISA (cat. no. BI-20472)

Rational engineering of glycosaminoglycan-based Dickkopf-1 scavengers to improve bone regeneration. Ruiz-Gómez G, Salbach-Hirsch J, Dürig JN, Köhler L, Balamurugan K, Rother S, Heidig SL, Moeller S, Schnabelrauch M, Furesi G, Pählig S, Guillem-Gloria PM, Hofbauer C, Hintze V, Pisabarro MT, Rademann J, Hofbauer LC. Biomaterials. 2023 Jun;297:122105. doi: 10.1016/j.biomaterials.2023.122105. Epub 2023 Mar 31. PMID: 37031548.

Abstract

The WNT signaling pathway is a central regulator of bone development and regeneration. Functional alterations of WNT ligands and inhibitors are associated with a variety of bone diseases that affect bone fragility and result in a high medical and socioeconomic burden. Hence, this cellular pathway has emerged as a novel target for bone-protective therapies, e.g. in osteoporosis. Here, we investigated glycosaminoglycan (GAG) recognition by Dickkopf-1 (DKK1), a potent endogenous WNT inhibitor, and the underlying functional implications in order to develop WNT signaling regulators. In a multidisciplinary approach we applied in silico structure-based de novo design strategies and molecular dynamics simulations combined with synthetic chemistry and surface plasmon resonance spectroscopy to Rationally Engineer oligomeric Glycosaminoglycan derivatives (_REGAG) with improved neutralizing properties for DKK1. In vitro and in vivo assays show that the GAG modification to obtain _REGAG translated into increased WNT pathway activity and improved bone regeneration in a mouse calvaria defect model with critical size bone lesions. Importantly, the developed _REGAG outperformed polymeric high-sulfated hyaluronan (sHA3) in enhancing bone healing up to 50% due to their improved DKK1 binding properties. Thus, rationally engineered GAG variants may represent an innovative strategy to develop novel therapeutic approaches for regenerative medicine