Standardizing Sclerostin Measurement

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.