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Type 2 Diabetes Mellitus (T2DM) and Cardiovascular (CV) diseases

Patients with T2DM have an elevated risk of developing CV diseases due to multiple factors. Chronic hyperglycemia, or elevated blood sugar levels, can cause damage to blood vessels promoting the development of atherosclerosis (1). Insulin resistance, a hallmark of T2DM, contributes to abnormal lipid profiles, such as increased triglycerides and low HDL cholesterol, both of which are risk factors for cardiovascular disease. Additionally, high blood sugar levels impair endothelial function, reducing the blood vessels’ ability to dilate properly and increasing the likelihood of plaque formation. T2DM is also associated with increased systemic inflammation, which accelerates the process of atherosclerosis. Moreover, patients with T2DM often develop increased arterial stiffness, further elevating cardiovascular risk (2).

Measuring Arterial Stiffness

Arterial stiffness is commonly measured using several non-invasive techniques, including Pulse Wave Velocity (PWV). PWV it the most widely used and regarded as the gold standard. It measures the speed at which the blood pressure pulse propagates through the arteries. A higher PWV indicates increased arterial stiffness. In patients with T2DM, arterial stiffness has been demonstrated to predict cardiovascular events independently of traditional risk factors, including glycemic control and 24-hour ambulatory blood pressure (3).

Sclerostin – A Biomarker for Vascular Risk in Diabetes

Sclerostin and DKK-1 in Type 2 Diabetes Mellitus (T2DM)

Sclerostin and DKK-1 are proteins that act as inhibitors of the Wnt signaling pathway, which is crucial for bone formation and remodeling (4).

In cardiovascular diseases, elevated levels of these proteins are associated with increased vascular calcification and atherosclerosis (5, 6). They influence the functioning of vascular cells and contribute to the development and progression of vascular damage.

In a recent study, researchers investigated the relationship of the biomarkers Sclerostin and DKK-1with peripheral arterial stiffness in patients with Type 2 Diabetes Mellitus (T2DM) (7). Sclerostin and DKK-1 were both successfully measured in serum samples using the ELISA assays from BIOMEDICA.

Key findings:

• Sclerostin, but not DKK-1 is independently associated with increased arterial stiffness in T2DM patients. 
• Circulating sclerostin may represent a potential biomarker of arterial stiffness in this population

 

The study highlights the potential of sclerostin as a biomarker for arterial stiffness and cardiovascular risk in diabetes.

SCLEROSTIN ELISA Assay | BI-20492

• most referenced in over 340 publications
• full validation package
• 20µl sample/well – serum and plasma – sample volume: 20µl / well

 

DKK-1 ELISA Assay | BI-20413

• highly cited in over 180 publications 
• full validation package
• 20µl sample/well – for serum  – sample volume: 20µl / well
• no sample pre-dilution – direct measurment

 

 

Positive Correlates of Sclerostin and Association with Peripheral Arterial Stiffness in Patients with Type 2 Diabetes Mellitus. Hsu B-G et al., Medicina. 2026

Abstract

Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate the correlation between sclerostin and DKK1 levels and PAS in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Biochemical data and sclerostin and DKK1 levels were analyzed in the fasting blood samples of 125 patients with T2DM. baPWV measurements using the VaSera VS-1000 automatic pulse wave analyzer classified patients with values > 18.0 m/s on either side into the PAS group. Results: Among patients with T2DM, 47 (37.6%) were classified as having PAS. These patients exhibited higher hypertension prevalence (p = 0.002); greater age (p < 0.001); elevated systolic (p < 0.001) and diastolic blood (p = 0.012) pressures; and increased fasting glucose (p = 0.001), glycated hemoglobin (p = 0.008), triglyceride (p = 0.001), blood urea nitrogen (p < 0.001), and creatinine (p = 0.001) levels, urine albumin-to-creatinine ratio (p = 0.039), and C-reactive protein (p = 0.024) and serum sclerostin (p < 0.001) levels, but decreased estimated glomerular filtration rate (p < 0.001). Multivariate logistic regression analysis identified serum sclerostin level (odds ratio, 1.127; 95% confidence interval, 1.058–1.200; p < 0.001) as an independent PAS predictor in patients with T2DM. Serum log-transformed sclerostin levels were positively correlated with left (p = 0.005) and right (p = 0.001) baPWV via Spearman’s rank-order correlation coefficient analysis. Conclusions: Serum sclerostin levels, but not DKK1 levels, are positively correlated with PAS in patients with T2DM.

Literature

1. 2-Fold More Cardiovascular Disease Events Decades Before Type 2 Diabetes Diagnosis: A Nationwide Registry Study. Gyldenkerne C, Kahlert J, Thrane PG, Olesen KKW, Mortensen MB, Sørensen HT, Thomsen RW, Maeng M.J Am Coll Cardiol. 2024 Dec 3;84(23):2251-2259. doi: 10.1016/j.jacc.2024.06.050. PMID: 39603746.
2. The Interplay Between Diabetes, Cardiovascular Disease, and Kidney Disease. Usman MS, Khan MS, Butler J. In: Chronic Kidney Disease and Type 2 Diabetes. Arlington (VA): American Diabetes
3. Association; 2021 Jun. PMID: 34279879.Prognostic impact of aortic stiffness in high-risk type 2 diabetic patients: the Rio deJaneiro Type 2 Diabetes Cohort Study. Diabetes Care. Cardoso CR, Ferreira MT, Leite NC, Salles GF. 2013 Nov;36(11):3772-8. doi: 10.2337/dc13-0506. Epub 2013 Jul 22. PMID: 23877987; PMCID: PMC3816863.
4. Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease. Ivanova MM, Dao J, Kasaci N, Friedman A, Noll L, Goker-Alpan O.Front Endocrinol (Lausanne). 2022 Nov 24;13:1029130. doi: 10.3389/fendo.2022.1029130. PMID: 36506070; PMCID: PMC9730525.
5. Sclerostin and Cardiovascular Disease. Tobias JH.Curr Osteoporos Rep. 2023 Oct;21(5):519-526. doi: 10.1007/s11914-023-00810-w. Epub 2023 Jul 25. PMID: 37490188; PMCID: PMC10543142.
6. Dickkopf-1, a potential target for heart disease. Xu P, Cao Y, Zhang S, Liu X, Zhang M, Zhang C.Int J Cardiol. 2024 Aug 1;408:132146. doi: 10.1016/j.ijcard.2024.132146. Epub 2024 May 9. PMID: 38729311.
7. Positive Correlates of Sclerostin and Association with Peripheral Arterial Stiffness in Patients with Type 2 Diabetes Mellitus. Hsu B-G, Li J-C, Wu D-A, Chen M-C. Medicina. 2026; 62(4):643.

 

 

 

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

Standardizing Sclerostin Measurement

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

Sclerostin and Type 2 Diabetes Mellitus

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

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

Key highlights:

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

 

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

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

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

 

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

 

 

Sclerostin ELISA (cat. no. BI-20492)

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

 

 

 

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

Abstract

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

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

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

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

Literature

1. Sclerostin: From Molecule to Clinical Biomarker. Omran A, Atanasova D, Landgren F, Magnusson P. Int J Mol Sci. 2022 Apr 26;23(9):4751. doi: 10.3390/ijms23094751. PMID: 35563144; PMCID: PMC9104784.
2. A practical approach for anabolic treatment of bone fragility with romosozumab. Cianferotti L, Cipriani C, Palermo A, Viapiana O, Zavatta G, Mazziotti G.J Endocrinol Invest. 2024 Nov;47(11):2649-2662. doi: 10.1007/s40618-024-02395-2. Epub 2024 May 24. PMID: 38789679.
3. Romosozumab. Krupa KN, Parmar M, Delo LF. 2024 Jul 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 36256789.
4. Skeletal Fragility in Type 2 Diabetes Mellitus. Starup-Linde J, Hygum K, Langdahl BL.Endocrinol Metab (Seoul). 2018 Sep;33(3):339-351. doi: 10.3803/EnM.2018.33.3.339. PMID: 30229573; PMCID: PMC6145952.
5. The association between sclerostin and incident type 2 diabetes risk: a cohort study. Yu OH, Richards B, Berger C, Josse RG, Leslie WD, Goltzman D, Kaiser SM, Kovacs CS, Davison KS. Clin Endocrinol (Oxf). 2017 Apr;86(4):520-525. doi: 10.1111/cen.13300. Epub 2017 Jan 26. PMID: 28090669.
6. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. García-Martín A, Rozas-Moreno P, Reyes-García R, Morales-Santana S, García-Fontana B, García-Salcedo JA, Muñoz-Torres M. J Clin Endocrinol Metab. 2012 Jan;97(1):234-41. doi: 10.1210/jc.2011-2186. Epub 2011 Oct 26. PMID: 22031520.
7. Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, Capodarca C, Franci MB, Campagna MS, Calabrò A, Cataldo D, Stolakis K, Dotta F, Nuti R. J Clin Endocrinol Metab. 2012 May;97(5):1737-44. doi: 10.1210/jc.2011-2958. Epub 2012 Mar 7. PMID: 22399511.
8. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. Yamamoto M, Yamauchi M, Sugimoto T. J Clin Endocrinol Metab. 2013 Oct;98(10):4030-7. doi: 10.1210/jc.2013-2143. Epub 2013 Jul 26. PMID: 23894157.
9. Association of total and bioactive serum sclerostin levels with bone metabolism in type 2 diabetes mellitus. Traechslin C, Sewing L, Baumann S, Grize L, Vavanikunnel J, Kraenzlin M, Henzen C, Meier C.J Clin Transl Endocrinol. 2025 Apr 8;40:100393. doi: 10.1016/j.jcte.2025.100393. PMID: 40275939; PMCID: PMC12019839.

 

 

 

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

Sclerostin is associated with risk for arterial stiffness

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

Sclerostin levels were measured with the

Biomedica SCLEROSTIN ELISA Assay | BI-20492

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

 

 

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

Literature:

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

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

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

Bone derived SCLEROSTIN is associated with Alzheimer´s Disease

Alzheimer’s disease and Wnt Signaling

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

Alzheimer’s disease and Sclerostin

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

Proposed Mechanism

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

Therapeutic Implications

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

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

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

 

 

Also available:

 Bioactive Sclerostin ELISA, BI-20472

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

 

Literature

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

 

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

Abstract

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

 

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

 

Sclerostin decreases through exercise and omega-3s

Key findings

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

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

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

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

 

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

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

 

About Sclerostin  

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

 

Literature

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

 

Abstract

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

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

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

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

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

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

 

 

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 

Blood Cancer Awareness – Exploring Multiple Myeloma and Bone Disease

Multiple myeloma is a hematological cancer, that disrupts normal hematopoiesis and bone marrow function. It is commonly associate with anemia, renal impairment, hypercalcemia, immunodeficiency, and osteolytic bone lesions. Bone disease is a hallmark of multiple myeloma and results from an imbalance in bone remodeling, with increased osteoclast-mediated bone resorption and suppressed osteoblast activity. 

In myeloma, bone disease is a serious problem that often causes pain and pathological bone fractures at different locations (1). Despite significant advances in therapeutic strategies that have improved outcomes and prolonged survival for patients with multiple myeloma, the disease remains largely incurable (2).

In multiple myeloma, tumor progression and associated bone disease are strongly influenced by interactions within the bone marrow microenvironment. However, not all cytokines or biomarker pathways contribute equally to the pathogenesis, progression, or prognosis of the disease. Among the most relevant mediators are IL-6, a key growth and survival factor for malignant plasma cells; RANKL, a central regulator of osteoclast activation and myeloma-related bone destruction; TNF-α, a pro-inflammatory cytokine involved in tumor–microenvironment interactions; and β-crosslaps (β-CTx), a marker of bone resorption that reflects increased osteoclast activity and skeletal turnover in multiple myeloma (3).

Blood Cancer Awareness – Exploring Multiple Myeloma and Bone Disease

The RANK/RANKL/OPG Axis in Bone Remodeling

The RANK/RANKL signaling axis plays a central role in bone metabolism and osteoclast differentiation. RANKL binds to its receptor, RANK, promoting osteoclast formation, activation, and bone resorption. Osteoprotegerin (OPG) functions as a soluble decoy receptor for RANKL, competitively binding RANKL and preventing its interaction with RANK. In this way, OPG helps inhibit osteoclast-mediated bone resorption and maintain bone remodeling balance (4).

A study on “ Bone Remodeling Markers in Children with Acute Lymphoblastic Leukemia after Intensive Chemotherapy” highlights how intensive chemotherapy can affect bone metabolism in pediatric Acute Lymphoblastic Leukemia (ALL) patients (5). A key focus is the OPG/RANKL pathway, which regulates osteoclast activity and bone resorption. By assessing osteoprotegerin (OPG) and RANKL, the study helps characterize a biochemical signature of altered bone remodeling after chemotherapy. These markers are especially relevant for understanding treatment-related bone fragility and long-term skeletal health in children with ALL.

The Role of Sclerostin and DKK-1 in Bone Remodeling

Sclerostin, also known as SOST, is primarily produced by osteocytes and is recognized as an important regulator of bone formation. It acts as a soluble antagonist of the Wnt signaling pathway, a pathway that plays a central role in bone homeostasis. Suppression of Wnt signaling is associated with reduced bone formation and increased bone degradation, whereas activation of this pathway promotes osteoblast activity and bone formation.

Dickkopf-1, or DKK-1, is a secreted extracellular protein that also functions as an inhibitor of the Wnt signaling pathway. By suppressing Wnt signaling, DKK-1 inhibits osteoblast differentiation and thereby reduces bone formation. Dysregulated DKK-1 expression has been linked to disturbed bone metabolism and may contribute to cancer progression (6).

Recent research highlights DKK-1 as a key mediator in multiple myeloma-associated bone disease. The study “Multi-Targeting DKK1 and LRP6 Prevents Bone Loss and Improves Fracture Resistance in Multiple Myeloma” shows that targeting the Wnt signaling pathway, including inhibition of DKK-1, may help protect against myeloma-induced bone loss and improve bone strength in preclinical models (7). These findings underline the importance of DKK-1 as a biomarker and research target in understanding bone remodeling, skeletal complications, and potential therapeutic strategies in multiple myeloma.

Biomedica offers quality kits for the measurement of 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)

 

 

Key highlights

• Trusted – cited in 1,000+ publications
• Reliable – validated kits following international quality guidelines
• Easy to use – color-coded, ready-to-use reagents

 

Literature

1. An overview of multiple myeloma: A monoclonal plasma cell malignancy’s diagnosis, management, and treatment modalities. Abduh MS. Saudi J Biol Sci. 2024 Feb;31(2):103920. doi: 10.1016/j.sjbs.2023.103920. Epub 2023 Dec 30. PMID: 38283805; PMCID: PMC10818257.
2. Redefining multiple myeloma treatment: Advances, challenges, and future directions in immunotherapy. Fu C, Zhai Y, Yan L, Jin S, Shang J, Shi X, Wu D. Chin Med J (Engl). 2025 Oct 5;138(19):2399-2410. doi: 10.1097/CM9.0000000000003655. Epub 2025 Aug 8. PMID: 40784898; PMCID: PMC12487921.
3. The Impact of Modern Bone Markers in Multiple Myeloma: Prospective Analyses Pre and Post-First Line Treatment. Pop VS, Iancu M, Țigu AB, Adam A, Tomoaia G, Farcas AD, Bojan AS, Parvu A. Curr Issues Mol Biol. 2024 Aug 24;46(9):9330-9341. doi: 10.3390/cimb46090552. PMID: 39329904; PMCID: PMC11430338.
4. 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.
5. 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.
6. Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma. Gerov V, Gerova D, Micheva I, Nikolova M, Mihaylova G, Galunska B. J Clin Med. 2023 Jul 1;12(13):4440. doi: 10.3390/jcm12134440. PMID: 37445475; PMCID: PMC10342782
7. Multi-Targeting DKK1 and LRP6 Prevents Bone Loss and Improves Fracture Resistance in Multiple Myeloma. Simic MK, Mohanty ST, Xiao Y, Cheng TL, Taylor VE, Charlat O, Croucher PI, McDonald MM. J Bone Miner Res. 2023 Jun;38(6):814-828. doi: 10.1002/jbmr.4809. Epub 2023 May 25. PMID: 36987921; PMCID: PMC10947379.

With more than 40 years of expertise in developing and manufacturing high-quality ELISA kits, we support scientists and healthcare professionals with reliable tests that drive discovery and help translate research into diagnostics.

All kits are developed and manufactured by Biomedica Immunoassays — Austrian quality you can trust.

Explore Our Biomarker ELISA Assays

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

Biomedica ELISA Kits: Features & Benefits

-Easy to use: Ready-to-use calibrators and controls included, with color-coded reagents

-Comprehensive validation package: Assays optimized for clinical samples in accordance with high-level international quality standards

-Guaranteed high quality: Reliable results you can trust

-Widely cited: Referenced in more than 2,500 publications

 

Biomedica provides high-quality ELISA kits for key bone biomarkers

Explore Our Biomarker ELISA Assays

 

BONE & MINERAL METABOLISM

 Biomedica provides high-quality ELISA kits for key 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. BI-20702)

PERIOSTIN ELISA – POSTN (cat. no. BI-20433)

 related citations:

• Sclerostin ELISA (BI-20492) and DKK-1 ELISA (BI-20413): Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4.
• FGF23 C-terminal (BI-20702) and FGF intact ELISA (BI-20700): C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival.  

 

CARDIOVASCULAR

NT-proBNP ELISA (cat.no. SK-1204)

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

NT-proANP,  ELISA human, rodent  (cat.no. BI-20892)

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

Big Endothelin-1 ELISA (cat. no. BI-20082H)

Endostatin ELISA (cat. no. BI-20742)

Leucine-rich alpha-2-glycoprotein (LRG) ELISA (cat. no. BI-LRG)

 related citations:

•  Big Endothelin-1 ELISA (cat. no. BI-20082H) : Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure.
• NT-proBNP ELISA (cat.no. SK-1204): Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model
• NT-proANP ELISA : Acute and Short‐Term Hemodynamic and Echocardiography Changes During and After Left Atrial Appendage Closure
• NT-proCNP ELISA (cat.no. BI-20812) : C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis

 

KIDNEY & TRANSPLANT

Vanin-1 (urine) ELISA  (cat. no. BI-VAN1U)

FGF23 intact ELISA – Fibroblast Growth Factor-23 intact (cat. no. BI-20700)

FGF23 C-terminal ELISA – Fibroblast Growth Factor-23 C-terminal (cat. no. BI-20702)

Human IL-6 ELISA Kit (cat. no.  BI-IL6)

Human Endostatin ELISA (cat. no. BI-20742)

Anti-C4d Antibody (cat. no. BI-RC4D)

related citations:

• Human Vanin-1 (urine) ELISA (cat. no. BI-VAN1U): Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease
• Vanin-1 ELISA (BI-VAN1U) and PERIOSTIN ELISA POSTN (cat. no. BI-20433): The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study

• Anti-C4d Antibody (cat. no. BI-RC4D): Thirty-year follow-up of immunosuppression modulation: Impact on graft fibrosis and anti-HLA antibodies after pediatric liver transplantation

 

ONCOLOGY

FREE soluble RANKL HS ELISA | BI-20462

Human Periostin ELISA | BI-20433

Human DKK1 ELISA Kit | BI-20413

Leucine-rich alpha-2-glycoprotein (LRG1) ELISA | BI-LRG

related citations:

• LRG-1 ELISA (BI-LRG): High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. 
• FREE soluble RANKL HS ELISA | BI-20462: Retrospective Evaluation of Bone Turnover Markers in Serum for the Prediction of Metastases Development in Breast Cancer Patients: A Cohort Study

 

OXIDATIVE STRESS 

 oLAB (Anti-Oxidized LDL Autoantibodies) ELISA | BI-20032

OxyStat Assay – detection of biological peroxides | BI-5007

related citations:

•  oxLDL – oLAB ELISA (BI-20032): Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology
• OxyStat Assay – The role of seminal reactive oxygen species assessment in the setting of infertility and early pregnancy loss

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About us

BIOMEDICA Immunoassays develops and manufactures high-quality, widely cited immunoassays for clinical and pre-clinical applications in bone and cardiorenal diseases. For selected biomarkers, BIOMEDICA has become a global leader, including Sclerostin, free sRANKL, OPG, and NT-proCNP.

All BIOMEDICA ELISA assays are fully validated according to international quality guidelines. The assays include ready-to-use serum-based calibrators and controls, helping researchers generate biologically reliable data.

 

Features & Benefits of BIOMEDICA ELISA Assay Kits

Trusted – cited in more than 2,500 publications

Highly specific – developed with well-characterized, epitope-mapped antibodies

Fully validated – comprehensive validation according to international quality guidelines

Convenient – ready-to-use, color-coded reagents with controls included

 

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

 –Intact FGF23 ELISA Kit | BI-20700

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

–Sclerostin ELISA | BI-20492

–FREE soluble RANKL HS ELISA | BI-20462

–Periostin ELISA | BI-20433

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

–NT-proBNP ELISA | SK-1204

–Rat NT-proBNP ELISA | BI-1204R

–NT-proANP ELISA | BI-20892

 

Selected citations

 Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort. Rasmussen, Kvist, Bech, Lykkeboe, Starup-Linde, Handberg, van den Bergh, Vestergaard; Osteoporos Int (2026) .

Endocrine Functions of Bone Are Suppressed by Orally Administered Glucose Regardless of Bodyweight. Jalava, Heino, Nuutila, Virtanen, Ivaska; Clin Endocrinol (Oxf) (2026) 104 (2), 130-138 .

Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth. Espiner, E., Prickett, T., Olney, R., 2018. Horm Res Paediatr 90, 345–357.

Subclinically low BMD in young men is associated with compromised bone microarchitecture and lower lean mass. Goulart, Kargl, Sterczala, Sekel, Wunderlich, Mroz, Lovalekar, Martin, Fazeli, Cauley, O’Leary, Greeves, Koltun, Nindl. J Endocr Soc (2026) 10 (3), bvag003.

 

 

 

 

The link between type 2 diabetes mellitus (T2DM) and bone fragility is complex. While individuals with type 2 diabetes often have normal to elevated bone mineral density, their risk of fractures is up to three times higher (1, 2).

Understanding Bone Health in Type 2 Diabetes

Recent research has shed new light on the complex relationship between Type 2 diabetes mellitus (T2DM) and bone health. The study, titled “Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort. Rasmussen NH et al., Osteoporos Int. 2026, provides valuable insights into how diabetes affects bone metabolism and fracture risk.

In this matched cross-sectional study, the researchers profiled Bone Status Indices (BSIs), which are biochemical markers of bone remodeling, in individuals with type 2 diabetes (T2D).

The BIOMEDICA assays bioactive Sclerostin and intact FGF23 were included in the study.

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

• Characterized antibodies that target the Sclerostin receptor binding region
• The assay is  validated for clinical samples  (validation data file)
• Only  20µl sample /well (protocol booklet)
• Widely cited

 

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

• Extensively validated according to international quality guidelines
• Correlates with existing methods (validation data file)
• One-step ELISA  (protocol booklet)
• Cited in top-tier journals

 

Key findings:

-Individuals with T2D have an increased risk of #fractures compared to those without diabetes.

-The elevated fracture risk persists even when bone mineral density (BMD) is normal or only slightly reduced.

-The researchers uncovered an altered bone remodeling processes in T2D, which could impact fracture risk and treatment strategies. 

Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort. Rasmussen NH, Kvist AV, Bech AA, Lykkeboe S, Starup-Linde J, Handberg A, van den Bergh JP, Vestergaard P. Osteoporos Int. 2026 Mar;37(3):703-716. doi: 10.1007/s00198-026-07850-9. Epub 2026 Jan 21. PMID: 41563408; PMCID: PMC13083425.

Abstract

People with type 2 diabetes have increased fracture risk despite preserved bone density. In this matched cross-sectional study, suppressed Bone Status Indices and exploratory sex-related hormonal associations were observed in T2D, indicating altered bone remodeling that is not captured by aBMD alone. These findings support the need for fracture risk assessment approaches that incorporate biochemical markers and potential sex-related differences.

Introduction/aim: People with type 2 diabetes (T2D) experience increased fracture risk despite preserved or higher areal bone mineral density (aBMD). We evaluated Bone Status Indices (BSIs) and their relationships with aBMD in T2D, with exploratory evaluation of sex-related hormonal influences.

Methods: In this matched cross-sectional study from the DiaFALL cohort, 105 adults with T2D were compared 1:1 with age- and sex-matched controls. aBMD was assessed at lumbar spine, femoral neck, arms, and legs using DXA. BSIs included intact PINP (i-PINP), β-CTX-I, osteocalcin (OCN), sclerostin, TRACP5b, IGF-1, OPN, PTH, and vitamin-D metabolites. Group differences and associations with aBMD were evaluated using multivariable regression and Spearman correlations, with exploratory sex-stratified analyses.

Results: Femoral-neck aBMD was higher in people with T2D (men: + 0.070 g/cm², 95%CI + 0.026 to + 0.114, p = 0.002; women: + 0.089, 95%CI + 0.039 to + 0.139, p = 0.001) and lumbar-spine aBMD was higher in women (+ 0.137 g/cm², 95%CI + 0.072 to + 0.202, p < 0.001). In contrast, multiple BSIs were suppressed in T2D, including i-PINP (men: Δ-12.8 µg/L, 95%CI -19.4 to -6.2, p = 0.002; women: Δ-13.6 µg/L, 95%CI -25.9 to -1.3, p = 0.002), osteocalcin (men: Δ-6.36 µg/L, 95%CI -9.15 to -3.57, p < 0.001; women: Δ-6.66 µg/L, 95%CI -11.0 to -2.20, p < 0.001), and β-CTX-I (men: Δ-40.5 ng/L, 95%CI -62 to -18, p = 0.012; women: Δ-110 ng/L, 95%CI -180 to -44, p = 0.014). Sclerostin was higher in men with T2D (Δ + 24.6 pmol/L, 95%CI + 1.5 to + 47.7, p = 0.019) and correlated positively with lumbar-spine aBMD (r = 0.411; p = 0.007). Furthermore, 1,25(OH)₂D (men p = 0.013; women p = 0.001) and magnesium (p = 0.002 both sexes) were lower in T2D despite similar PTH. No significant T2D-sex interactions were observed for any BSI (all p > 0.05).

Conclusion: T2D was characterized by higher aBMD together with broadly suppressed BSIs, consistent with a low-turnover skeletal phenotype not captured by DXA alone. Osteocalcin og sclerostin appeared most informative. These findings support longitudinal studies to determine whether BSIs can enhance identification of skeletal fragility in T2D.

 

Literature

1. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Picke AK, Campbell G, Napoli N, Hofbauer LC, Rauner M. Endocr Connect. 2019 Mar 1;8(3):R55-R70. doi: 10.1530/EC-18-0456. PMID: 30772871; PMCID: PMC6391903.
2. Bone Health in Patients With Type 2 Diabetes. Forner P, Sheu A. J Endocr Soc. 2024 Jun 6;8(7):bvae112. doi: 10.1210/jendso/bvae112. PMID: 38887632; PMCID: PMC11181004.

 

Related Reviews

Bone fragility in diabetes: novel concepts and clinical implications. Hofbauer LC, Busse B, Eastell R, Ferrari S, Frost M, Müller R, Burden AM, Rivadeneira F, Napoli N, Rauner M.Lancet Diabetes Endocrinol. 2022 Mar;10(3):207-220. doi: 10.1016/S2213-8587(21)00347-8. Epub 2022 Jan 31. PMID: 35101185.

Contributors to impaired bone health in type 2 diabetes. Sheu A, Greenfield JR, White CP, Center JR. Trends Endocrinol Metab. 2023 Jan;34(1):34-48. doi: 10.1016/j.tem.2022.11.003. Epub 2022 Nov 23. PMID: 36435679.

Approximately 1 in 10 people are affected by chronic kidney disease (CKD), impacting over 800 million individuals globally (1-3). CKD is a progressive condition where the kidneys gradually lose their ability to function properly.

Early intervention is essential to preserving kidney health, slowing the progression of kidney disease and its complications, decreasing the risk of risk of cardiovascular disease, and preventing early death related to kidney and cardiovascular conditions (4).

World Kidney Day – March 12, 2026

What are the contributing factors to CKD?

Age over 60, diabetes, high blood pressure, heart disease, obesity, and certain medications are some of the known risk factors for kidney disease. 

 How can we maintain healthy kidneys?

Good nutrition, regular exercise, and adequate fluid intake are some of the ways to support kidney health.

Are your kidneys healthy? Take the quiz

 

 BIOMEDICA´s Biomarker ELISA Kits in Clinical Nephrology

• FGF23 (C-terminal) |BI-20700 and FGF23 intact ELISA |BI-20700
• Vanin-1 (urine) ELISA | BI-VAN1U  
• Endostatin ELISA | BI-20742
• Periostin ELISA | BI-20422
• Sclerostin ELISA |BI-20492 and Bioactive Sclerostin ELISA |BI-20472

 

 

Related Products:

Osteoprotegerin ELISA, NT-proBNP ELISA, Anti-C4d Antibody

Why laboratories choose BIOMEDICA ELISA kits

• ROBUST & RELIABLE ASSAYS
• Widely cited in over 1700 peer-reviewed publications
• Validated according to international guidelines
• High specificity, enabling reliable biomarker measurement in healthy individuals

 

Are you planning a clinical study ELISA kits for clinical research in kidney disease

Biomarkers in Clinical Nephrology – check out our broshure

 More information on kidney health can be found on the following websites:

1. ISN, World Kidney Day 2026 – International Society of Nephrology
2. Are your kidneys healthy- Quiz – 20 years World Kidney Day
3. Detect early, protect kidney health: World Kidney Day 2025. Waith FM, Bresolin NL, Antwi S. Pediatr Nephrol. 2025 May;40(5):1511-1514. doi: 10.1007/s00467-025-06714-4. Epub 2025 Feb 17. PMID: 39960639. For full publication- click here 
4. Are your kidneys ok? Detect early to protect kidney health. Vassalotti JA, Francis A, Soares Dos Santos AC Jr, Correa-Rotter R, Abdellatif D, Hsiao LL, Roumeliotis S, Haris A, Kumaraswami LA, Lui SF, Balducci A, Liakopoulos V; World Kidney Day Joint Steering Committee. Ren Fail. 2025 Dec;47(1):2503514. PMID: 40394853

 

Abstract

Early identification of kidney disease can protect kidney health, prevent kidney disease progression and related complications, reduce cardiovascular disease risk and decrease mortality. We must ask “Are your kidneys ok?” using serum creatinine to estimate kidney function and urine albumin to assess for kidney and endothelial damage. Evaluation for causes and risk factors for chronic kidney disease (CKD) includes testing for diabetes and measurement of blood pressure and body mass index. This World Kidney Day we assert that case-finding in high-risk populations, or even population level screening, can decrease the burden of kidney disease globally. Early-stage CKD is asymptomatic, simple to test for and recent paradigm shifting CKD treatments such as sodium glucose co-transporter-2 inhibitors dramatically improve outcomes and favor the cost-benefit analysis for screening or case-finding programs. Despite this, numerous barriers exist, including resource allocation, healthcare funding, healthcare infrastructure and healthcare-professional and population awareness of kidney disease. Coordinated efforts by major kidney non-governmental organizations to prioritize the kidney health agenda for governments and aligning early detection efforts with other current programs will maximize efficiencies.

Additonal publications:

IPNA’s commitment to world kidney day 2026: caring for little kidneys and protecting the planet. Shroff R, Sivaram P, Tarter A, Phiri EM, Antwi S, Ocheke I, Penido MG, Mccarthy F, Lou-Meda R, Adalat S, He G, Kermond R, Bayazit AK, Raina R; IPNA Green Nephrology Taskforce, IPNA Special Projects Committee. Pediatr Nephrol. 2026 Feb 24. PMID: 41733668.

Children and adolescents with type 1 diabetes (T1D) frequently encounter issues related to bone health. Research consistently shows that young individuals with T1D have lower bone mineral density (BMD) than their healthy counterparts. Moreover, children with T1D exhibit compromised bone microarchitecture and decreased bone turnover. Together, these factors heighten the risk of fractures throughout their lifetime (1). In addition, advanced imaging techniques have revealed that the negative impact of T1D on the growing skeleton goes beyond reduced bone density, affecting bone size, shape, and strength (2).

Type 1 diabetes in adolescents linked to low bone mass and altered bone biomarkers

In a recent study, researchers investigated whether adolescents with well-controlled, long-duration type 1 diabetes (T1D) have differences in bone mass and bone biomarkers in comparison with healthy individuals (3). The researchers measured various biomarkers including receptor activator nuclear factor κB ligand (RANKL*), Osteoprotegerin (OPG*), Sclerostin (SOST*), and C-terminal telopeptide of type I collagen (CTX).

Highlights

• Type 1 diabetes (T1D) is linked to a higher risk of fractures.
• Prolonged T1D leads to low bone mass and impaired microarchitecture.
• The T1D group showed decreased levels of RANKL and CTX.

 

In summary: young people with long-term T1D show decreased gain in bone mass, impaired microarchitecture, and suppressed RANKL-driven osteoclast formation, leading to decreased bone resorption. Monitoring bone health is recommended for adolescents with T1D.

*Biomedica ELISA kits were used in this study.

BIOMEDICA´s ELISA kit highlights:
• Widely cited in clinical studies
• Reliable – validated according to international guidelines
• High sensitivity – measurable concentrations in healthy subjects
• HIGH quality guaranteed 

FREE soluble RANKL HS ELISA | BI-20462

•  High sensitivity – measurable concentrations in healthy subjects
• Only ELISA that measures free, uncomplexed soluble RANKL

 

 

Literature

1. Bone Health in Children and Adolescents with Type 1 Diabetes: Optimizing Bone Accrual and Preventing Fractures. Levran N, Shalev-Goldman E, Levy-Shraga Y. Nutrients. 2025 Jul 23;17(15):2400. doi: 10.3390/nu17152400. PMID: 40805986; PMCID: PMC12348532.
2. Bone accrual in children and adolescents with type 1 diabetes: current knowledge and future directions. Weber DR Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):340-347. doi: 10.1097/MED.0000000000000638. PMID: 33965967.
3. Adolescents with long-duration type 1 diabetes have low bone mass and reduced levels of bone indices reflecting altered bone resorption. Swolin-Eide D, Pundziute Lyckå A, Novak D, Andersson B, Forsander G, Magnusson P.Bone. 2025 Oct;199:117560. doi: 10.1016/j.bone.2025.117560. Epub 2025 Jun 4. PMID: 40480641.

Intense exercise and load carriage can lead to high mechanical and metabolic stress on the skeleton, disrupting calcium metabolism (1). Studies have shown that load carriage exercise increases calcium absorption and retention in healthy young women (2). Integrating women into military service necessitates research on gender-specific effects of military training and operational activities (3). In a randomized controlled crossover trial researchers investigated the effect of calcium supplementation on calcium and bone metabolism in women during load carriage (1).  

The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomized controlled crossover trial. Coombs CV et al., 2025.

Study details:

• a total of 48 women volunteered for the study, including 38 military personnel and 10 civilians.
• each participant completed two load carriage exercise sessions in a randomized order:

•  One session after taking a 1000 mg calcium supplement, 60 minutes prior to load carriage
•  One session without any supplement (control)

• during each session, participants walked 12.8 km on a treadmill at a speed of 6.4 km/h for 120 minutes while carrying a 20 kg rucksack.

Calcium supplementation and bone health in woman during load carriage

Key findings:

• Intense exercise stresses the skeleton and disrupts calcium metabolism.
• Calcium supplementation leads to increased serum ionized calcium, reduced PTH levels, and decreased bone resorption.
• Calcium supplementation had no effect on markers of bone formation, including Sclerostin.
• Taking 1000 mg of calcium 60 minutes before load carriage helps protect bone health and calcium balance.

 

SCLEROSTIN was measured with the BIOMEDICA Sclerostin assay:

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

• Most referenced Sclerostin ELISA in over 330 citations
• Low sample volume – 20µl / well
• Full validation package – download here

 

 

Related products:

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

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

FREE soluble RANKL HS ELISA (cat. no BI-20462)

 

Literature:

1. The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomized controlled crossover trial. Coombs CV, Greeves JP, Young CD, Irving AS, Eisenhauer A, Kolevica A, Heuser A, Tang JCY, Fraser WD, O’Leary TJ. J Bone Miner Res. 2025 Jun 3;40(6):753-765. doi: 10.1093/jbmr/zjaf004. PMID: 39804018.
2. Load carriage exercise increases calcium absorption and retention in healthy young women. Gaffney-Stomberg E, Nakayama AT, Lutz LJ, McClung JP, O’Brien KO, Staab JS. J Bone Miner Res. 2024 Mar 4;39(1):39-49. doi: 10.1093/jbmr/zjad003. PMID: 38630876.
3. Load carriage changes tibiofemoral arthrokinematics during ambulatory tasks in recruit-aged women. Johnson CC, Dzewaltowski AC, Dever DE, Krajewski KT, Rai A, Ahamed NU, Allison KF, Flanagan SD, Graham SM, Lovalekar M, Anderst WJ, Connaboy C. Sci Rep. 2024 Apr 25;14(1):9542. doi: 10.1038/s41598-024-60187-3. PMID: 38664550; PMCID: PMC11045865.

 

 

 

Nearly 10% of the world’s population suffer from lower back pain (LBP) (1, 2). Lumbar traction therapy is a non-invasive treatment for LBP that involves gently stretching the spine to relieve pressure on the vertebral discs and nerves (3). In a first-time study, researchers investigated the influence of long-term application of traction forces on the size of vertebrae, bone mineral density (BMD), and bone turnover markers in women LBP (4).

Impact of traction therapy on bone in women with chronic back pain

The BIOMEDICA free soluble RANKL (sRANKL) ELISA assay and bioactive Sclerostin ELISA assay were utilized in the study to quantify soluble RANKL and bioactive Sclerostin levels in human serum.

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

• Highly sensitive – measurable concentrations in healthy individuals
• Only ELISA that measures free, uncomplexed soluble RANKL
• Widely cited in more than 325 publications

 

Bioactive SCLEROSTIN ELISA assay kit (cat.no. BI-20472) 

• Reliable – validated according to international guidelines
• Specific – high quality antibodies targeting the receptor binding region
• Low sample volume – 20 µl of serum/plasma per well 
• Citations

 

Bone remodelling after application of traction forces to the lumbar spine in women with chronic low back pain. Ratajczak M, Kusy K, Skrypnik D, Waszak M, Krutki P. Bone Joint Res. 2025 Aug 4;14(8):674-684. doi: 10.1302/2046-3758.148.BJR-2024-0465.R1. PMID: 40754314; PMCID: PMC12318618.

Abstract

Aims: The aim of the study was to investigate the effect of systematic lumbar traction, applied in 20 sessions over four weeks, on the size of vertebrae, bone mineral density (BMD), and bone turnover markers in women with chronic low back pain (LBP).

Methods: A total of 30 women with low back pain underwent 20 sessions of lumbar traction with a load of 25% to 30% of their body weight. Total body and lumbar spine BMD was measured using dual-energy X-ray absorptiometry, and bone turnover markers were determined using enzyme-linked immunosorbent assay (ELISA) with serum samples collected before the first traction session and 72 hours after the last traction session.

Results: After traction, decreased BMD and T-scores, a decreased mean vertebra width, and an increased mean height of L1-L4 segments were observed. The concentration of cross-linked C-telopeptide of type I collagen (CTXI) increased, while the concentration of receptor activator for nuclear factor κ B ligand (RANKL) decreased significantly after four weeks of traction. Sclerostin and procollagen 1 N-terminal propeptide (P1NP) concentrations remained unchanged.

Conclusion: Our study is the first to show the influence of traction forces on BMD and markers of bone metabolism. Future research with a longer follow-up period after traction is needed to better explore the direction of change.

 

Literature

1. The global epidemic of low back pain. Lancet Rheumatol. 2023 Jun;5(6):e305. doi: 10.1016/S2665-9913(23)00133-9. PMID: 38251593.
2. Low back pain, WHO, 2023.
3. What Is Traction Therapy, and How Does it Work? ERA Health.
4. Bone remodelling after application of traction forces to the lumbar spine in women with chronic low back pain. Ratajczak M, Kusy K, Skrypnik D, Waszak M, Krutki P. Bone Joint Res. 2025 Aug 4;14(8):674-684. doi: 10.1302/2046-3758.148.BJR-2024-0465.R1. PMID: 40754314; PMCID: PMC12318

Type 1 diabetes mellitus is an autoimmune disorder marked by the destruction of pancreatic islet cells, resulting in an absolute deficiency of insulin. Multiple mechanisms have been recognized to explain the skeletal fragility observed in T1DM, including reductions in bone mineral density (BMD), alterations in bone geometry, impaired bone microarchitecture, and compromised biomechanical properties, as evidenced in both humans and animal models of T1DM. Previous meta-analyses have shown that individuals with T1DM face a four- to sevenfold higher risk of hip fractures compared to controls (1, 2).

How Type 1 Diabetes affects Bone Health

In a recent cross-sectional clinical study researchers explored the differences in bone turnover markers (BTMs) and their correlations with areal mineral density (aBMD) in people with type 1 diabetes (T1D), to gain deeper insights into the mechanisms of skeletal fragility, including differences related to sex and hormonal factors (3).

Both the Biomedica BIOACTIVE SCLEROSTIN ELISA Assay and the FGF23 INTACT ELISA Assay were featured in this study.  

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

• Characterized antibodies that target the Sclerostin receptor binding region
• The assay is  validated for clinical samples  (validation data file)
• Only  20µl sample /well (protocol booklet)
• Widely cited

 

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

• Extensively validated according to international quality guidelines
• Correlates with existing methods (validation data file)
• One-step ELISA  (protocol booklet)
• Cited in top-tier journals

 

Bone turnover markers and mineral density in type 1 diabetes – A cross-sectional study: DIAFALL. Rasmussen NH et al., Bone. 2025.

Abstract

Introduction/aim: This study investigated differences in bone turnover markers (BTMs) and their associations with areal bone mineral density (aBMD) in people with type 1 diabetes (T1D) to better understand the mechanisms underlying skeletal fragility, including sex- and hormone-related variations.

Methods: A cohort of 110 Caucasian participants with T1D were matched 1: 1 with age- and sex-matched controls. aBMD at the lumbar spine, femoral neck, legs, and arms was assessed using DXA. BTMs included P1NP, osteocalcin (OC), sclerostin, CTX-1, TRAcP, IGF-1, BASP, and osteopontin (OPN). Group comparisons were conducted using t-tests, and associations between BTMs and aBMD were examined using regression and Spearman correlations. Exploratory subgroup analyses stratified women by menopausal status.

Results: Bone formation markers (P1NP, OC) were significantly lower in T1D men compared to controls (P1NP: p = 0.046; OC: p = 0.002), reflecting suppressed bone formation. IGF-1 was reduced in both sexes (p < 0.001) and correlated positively with aBMD in women (p < 0.05), but not in men. Sclerostin levels were elevated in both sexes (p = 0.002-<0.001) without correlating with aBMD. CTX-1 was reduced in T1D men (p = 0.004), while TRAcP was elevated in both sexes (p = 0.044), correlating negatively with aBMD in women. Men with T1D had significantly lower leg aBMD (p = 0.032) and reduced femoral neck bone mineral content (p = 0.041). No overall differences were observed among women; however, exploratory analyses revealed that postmenopausal women with T1D had higher TRAcP and sclerostin levels and lower femoral neck aBMD compared to premenopausal counterparts.

Conclusion: T1D was associated with significant alterations in certain BTMs and reduced aBMD in men, while skeletal effects in women appeared to be influenced by menopausal status. The weak and mostly non-significant correlations between BTMs and aBMD suggest that impaired bone quality, rather than bone mass alone, may be the primary driver of skeletal fragility in T1D. Hormonal status may further modify these effects in women.

 

Literature

1. Fracture risk in young and middle-aged adults with type 1 diabetes mellitus: A systematic review and meta-analysis. Thong EP, Herath M, Weber DR, Ranasinha S, Ebeling PR, Milat F, Teede H. Clin Endocrinol (Oxf). 2018 Sep;89(3):314-323. doi: 10.1111/cen.13761. Epub 2018 Jul 3. PMID: 29876960; PMCID: PMC6105385.
2. Bone fragility in diabetes: novel concepts and clinical implications. Hofbauer LC, Busse B, Eastell R, Ferrari S, Frost M, Müller R, Burden AM, Rivadeneira F, Napoli N, Rauner M. Lancet Diabetes Endocrinol. 2022 Mar;10(3):207-220. doi: 10.1016/S2213-8587(21)00347-8. Epub 2022 Jan 31. PMID: 35101185.
3. Bone turnover markers and mineral density in type 1 diabetes – A cross-sectional study: DIAFALL. Rasmussen NH, Kvist AV, Lykkeboe S, Starup-Linde J, Handberg A, van den Bergh JP, Vestergaard P. Bone. 2025