Download biomedica product listSclerostin ELISA | BI-20492
- New finding: Sclerostin in Alzheimer´s Disease
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Method
Sandwich ELISA, HRP/TMB, 12×8-well detachable strips
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Sample type
Serum, EDTA plasma, citrate plasma, heparın plasma, urine, cell culture supernatant
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Sample volume
20 µl / well
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Assay time
18-24 h / 1 h / 30 min
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Sensitivity
3.2 pmol/l (= 72 pg/ml)
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Standard range
0 – 240 pmol/l (= 0 – 5,400 pg/ml)
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Conversion factor
1 pmol/l = 22.5 pg/ml (MW: 22.5 kDa)
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Precision
In-between-run (n=6): ≤ 10 % CV
Within-run (n=8): ≤ 7 % CV
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Specificity
Endogenous and recombinant human Sclerostin.
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Cross-reactivity
The assay does not cross-react with Wise (Sostdc1) or Noggin. The assay does not cross-react with rat or mouse Sclerostin.
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Use
Research use only
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Validation Data
See validation data tab for: precision, accuracy, dilution linearity, values for healthy donors, etc
Sclerostin ELISA Product Overview
The human Sclerostin ELISA kit is an overnight, 96-well sandwich ELISA for the quantitative determination of human Sclerostin in serum, plasma, urine and cell culture supernatant. The Sclerostin ELISA employs human serum-based standards to ensure the measurement of biologically reliable data.
The Sclerostin ELISA assay uses highly purified, epitope mapped antibodies.
Sclerostin ELISA Assay Principle
The Sclerostin ELISA kit is a sandwich enzyme immunoassay for the quantitative determination of Sclerostin (SOST) in human serum, plasma, urine and cell culture supernatnat samples.
The figure below explains the principle of the Sclerostin sandwich ELISA:
Capture antibody: polyclonal goat anti-human Sclerostin antibody
Detection antibody: monoclonal mouse anti-human Sclerostin antibody, biotin labeled
Target antigen: human Sclerostin
In a first step, assay buffer is pipetted into the wells of the microtiter strips. Thereafter, standard/control/sample and detection antibody (biotinylated monoclonal mouse anti-human Sclerostin) are pipetted into the wells, which are pre-coated with polyclonal goat anti-human Sclerostin antibody. Any Sclerostin present in the standard/control/sample binds to the pre-coated antibody in the well and forms a sandwich with the detection antibody. In a washing step, all non-specific unbound material is removed. In a next step, the conjugate (strepdavidin-HRP) is pipetted into the wells and reacts with the detection antibody. After another washing step, the substrate (tetramethylbenzidine, TMB) is pipetted into the wells. The enzyme-catalyzed color reaction of the substrate is directly proportional to the amount of Sclerostin present in the sample. This color change is detectable with a standard microtiter plate reader. A dose response curve of the absorbance (optical density, OD, at 450 nm) versus standard concentration is generated, using the values obtained from the standards. The concentration of human Sclerostin in the sample is determined directly from the dose response curve.
Sclerostin ELISA Typical Standard Curve
The figure below shows a typical standard curve for the human Sclerostin ELISA. The immunoassay is calibrated against human recombinant Sclerostin peptide:
Sclerostin ELISA Kit Components
|
Contents |
Description |
Quantity |
|
PLATE |
Polyclonal goat anti-human Sclerostin antibody pre-coated microtiter strips in a strip holder, packed in an aluminum bag with desiccant |
12 x 8 tests |
|
WASHBUF |
Wash buffer concentrate 20 x, natural cap |
1 x 50 ml |
|
STD |
Standards 1-6, (0; 15; 30; 60; 120; 240 pmol/l), recombinant human Sclerostin in human serum, white caps, lyophilized |
6 vials |
|
CTRL |
Control, yellow cap, lyophilized, exact concentration on the label |
1 vial |
|
ASYBUF |
Assay buffer, red cap, ready to use |
1 x 20 ml |
|
AB |
Monoclonal mouse anti-human Sclerostin antibody, biotinylated, green dye, green cap, ready to use |
1 x 7 ml |
|
CONJ |
Conjugate (streptavidin-HRP), amber bottle, amber cap, ready to use |
1 x 22 ml |
|
SUB |
Substrate (TMB solution), amber bottle, blue cap, ready to use |
1 x 22 ml |
|
STOP |
Stop solution, white cap, ready to use |
1 x 7 ml |
Storage instructions: all reagents of the Sclerostin ELISA kit are stable at 4°C (2-8°C) until the expiry date stated on the label of each reagent.
Serum, EDTA plasma, heparın plasma, citrate plasma, cell culture supernatant and urine are suitable for use in this Biomedica Sclerostin assay. Do not change sample type during studies. We recommend duplicate measurements for all samples, standards and controls. The sample collection and storage conditions listed are intended as general guidelines.
Serum & Plasma
Collect venous blood samples in standardized serum separator tubes (SST) or standardized blood collection tubes using EDTA, heparın or citrate as an anticoagulant. For serum samples, allow samples to clot for 30 minutes at room temperature. Perform separation by centrifugation according to the tube manufacturer’s instructions for use. Assay the acquired samples immediately or aliquot and store at -25°C or lower. Lipemic or haemolyzed samples may give erroneous results. Samples can undergo at least four freeze-thaw cycles.
Cell Culture Supernatant
Note: the experiments performed to measure Sclerostin in cell culture supernatant samples did not undergo a full validation according to FDA/ICH/EMEA guidelines. However, our performance check suggests that cell culture supernatant samples can be measured with this ELISA.
Remove particulates by centrifugation and assay immediately or aliquot and store samples at -25°C or lower.
Urine
Note: the experiments performed to measure bioactive Sclerostin in urine samples did not undergo a full validation according to FDA/ICH/EMEA guidelines. However, our performance check suggests that urine samples can be measured with this ELISA. For more information please see our validation data file.
Aseptically collect the first urine of the day (mid-stream), voided directly into a sterile container. Centrifuge to remove particulate matter, assay immediately or aliquot and store at -25°C or lower.
Reagent Preparation
Wash Buffer
|
1. |
Bring the WASHBUF concentrate to room temperature. Crystals in the buffer concentrate will dissolve at room temperature. |
|
2. |
Dilute the WASHBUF concentrate 1:20, e.g. 50 ml WASHBUF + 950 ml distilled or deionized water. Only use diluted WASHBUF when performing the assay. |
The diluted WASHBUF is stable up to one month at 4°C (2-8°C).
Standards
|
1. |
Pipette 400 µl of distilled or deionized water into each standard (STD) and control (CTRL) vial. The exact concentration is printed on the label of each vial. |
|
2. |
Leave at room temperature (18-26°C) for 15 min. Vortex gently. |
Reconstituted STDs and the CTRL are stable at -25°C or lower until expiry date stated on the label. Avoid repeated freeze-thaw cycles.
Sample Preparation
Bring samples to room temperature and mix samples gently to ensure the samples are homogeneous. We recommend duplicate measurements for all samples.
Samples for which the OD value exceeds the highest point of the standard range can be diluted with ASYBUF (assay buffer).
Sclerostin ELISA Assay Protocol
Read the entire protocol before beginning the assay.
|
1. |
Bring samples and reagents to room temperature (18-26°C). |
|
2. |
Mark positions for STD/CTRL/SAMPLE (standard/control/sample) on the protocol sheet. |
|
3. |
Take microtiter strips out of the aluminum bag. Store unused strips with desiccant at 4°C in the aluminum bag. Strips are stable until expiry date stated on the label. |
|
4. |
Pipette 150 µl ASYBUF (assay buffer, red cap) into each well. |
|
5. |
Add 20 µl STD/CTRL/SAMPLE into the respective wells. |
|
6. |
Add 50 µl AB (biotinylated anti-Sclerostin antibody, green cap, green dye) into each well. Swirl gently. |
|
7. |
Cover tightly and incubate overnight (18-24 h) at room temperature (18-24°C) in the dark. Attention: Incubation higher than room temperature reduces the top OD. |
|
8. |
Aspirate and wash wells 5 x with 300 µl diluted WASHBUF (wash buffer). After the final wash, remove the remaining WASHBUF by strongly tapping plate against a paper towel. |
|
9. |
Add 200 µl CONJ (conjugate, amber cap) into each well. |
|
10. |
Cover tightly and incubate for 1 hour at room temperature in the dark. |
|
11. |
Aspirate and wash wells 5 x with 300 µl diluted WASHBUF. After the final wash, remove remaining WASHBUF by strongly tapping plate against a paper towel. |
|
12. |
Add 200 µl SUB (substrate, blue cap) into each well. |
|
13. |
Incubate for 30 min at room temperature in the dark. |
|
14. |
Add 50 µl STOP (stop solution, white cap) into each well. |
|
15. |
Measure absorbance immediately at 450 nm with reference 630 nm, if available. |
Calculation of Results
Read the optical density (OD) of all wells on a plate reader using 450 nm wavelength (reference wavelength 630 nm). Construct a standard curve from the absorbance read-outs of the standards using commercially available software capable of generating a four-parameter logistic (4-PL) fit. Alternatively, plot the standards’ concentration on the x-axis against the mean absorbance for each standard on the y-axis and draw a best fit curve through the points on the graph. Curve fitting algorithms other than 4-PL have not been validated and will need to be evaluated by the user.
Obtain sample concentrations from the standard curve. If required, pmol/l can be converted into pg/ml by applying a conversion factor (1 pg/ml = 0.044 pmol/l (MW: 22.5 kD)). Respective dilution factors must be considered when calculating the final concentration of the sample.
The quality control protocol supplied with the kit shows the results of the final release QC for each kit at production date. Data for OD obtained by customers may differ due to various influences including the normal decrease of signal intensity throughout shelf life. However, this does not affect validity of results as long as an OD of 1.00 or higher is obtained for the standard with the highest concentration and the control value is in range (target range see label).
Sclerostin Protein
Sclerostin is a 22.5 kDa secreted glycoprotein that functions as a potent inhibitor of Wnt signaling. It acts by binding to the Wnt-coreceptor LRP5/6 thus inhibiting bone formation by regulating osteoblast function and promoting osteoblast apoptosis. The Sclerostin protein consists of two flexible N- and C-terminal arms and a cystine-knot with three loops, whereas the second loop binds to the LRP5/6 complex. Sclerostin is classically considered to be a monomeric protein, but data from Hernandez and colleagues (Hernandez et al., 2014) postulate that circulating sclerostin has a dimeric configuration. In addition, it is not yet well documented if also Sclerostin fragments circulate, but the comparison of different Sclerostin ELISAs suggest that fragments exist as well (Dallas et al., 2013).
|
Molecular weight |
22.5 kDa |
|
Cellular localization |
Extracellular |
|
Post-translational modifications |
Glycosylation |
|
Sequence similarities |
Sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists |
|
Alternative names |
CDD, VBCH, DAND6, SOST1, SOST |
|
Entrez/NCBI ID |
|
|
Genecards |
|
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OMIM |
|
|
Protein Atlas |
|
|
Uniprot ID |
Sclerostin Function
Sclerostin is nearly exclusively produced in osteocytes (van Bezooijen et al., 2009). Mutations in the Sclerostin (SOST) gene can cause sclerosteosis and van Buchem disease which are bone dysplasia disorders characterized by progressive skeletal overgrowth (Wergedal et al., 2003). Sclerostin levels are altered in response to hormonal stimuli or due to pathophysiological conditions. Sclerostin concentrations are increased in disorders such as hypoparathyroidism (Costa et al., 2011), Paget’s disease (Yavropoulou et al., 2012), multiple myeloma (Terpos et al., 2012) and in cancer induced bone diseases (Yavropoulou et al., 2012). Sclerostin levels are decreased in primary hyperparathyroidism (Lierop et al., 2010), as well as by the mechanical stimulation of bone (Robling et al., 2008). Several studies have found a positive association between sclerostin and bone mineral density (Amrein et al., 2012; Garnero et al., 2013). Sclerostin levels in chronic kidney disease (CKD) patients are increased up to 4-fold compared to patients without CKD and increase with CKD stage and declining kidney function (Cejka et al., 2012; Pelletier et al., 2013). In CKD patients, renal elimination of sclerostin increases with decreasing renal function (Cejka et al., 2014). In dialysis patients, sclerostin is an independent predictor of bone loss (Malluche et al., 2014). Numerous studies have shown that serum sclerostin levels are also associated with cardiovascular events (Kanbay et al., 2014; Viaene et al., 2013). The FDA authorization of a humanized monoclonal Sclerostin antibody for the treatment of osteoporosis in patients at high risk is currently under investigation (McClung, 2017). For reviews please refer to the following references: Costa et al., 2017; Drake and Khosla, 2017.
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Cardiovascular Diseases
- Vascular calcification in chronic kidney disease patients
- Peripheral artery disease
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Endocrine disorders
- Primary hyperparathyroidism
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Inflammation
- Chronic inflammation
- Rheumatoid arthritis
- Ankylosing spondylitis
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Kidney Disease
- Chronic kidney disease
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Oncology
- Multiple myeloma
- Bone metastatic breast cancer
- Bone metastatic prostate cancer
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Other
- Therapy monitoring of anabolic treatment
Literature
Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis. Hamar A., Szekanecz Z., Pusztai A., Czókolyová M., Végh E., Pethő Z., Bodnár N., Gulyás K., Horváth Á., Soós B., et al., 2021. Osteoporos Int doi: 10.1007/s00198-021-05871-0. Epub ahead of print. PMID: 33559714.
Relationship between sclerostin and coronary tortuosity in postmenopausal females with non-obstructive coronary artery disease. Ibrahim IM., Farag EM., Tabl MAE., Abdelaziz M., 2021. Int J Cardiol 322:29-33.
Serum sclerostin and glucose homeostasis: No association in healthy men. Cross-sectional and prospective data from the EGIR-RISC study. Lauterlein JL., Hermann P., Konrad T., Wolf P., Nilsson P., Sánchez RG., Ferrannini E., Balkau B., Højlund K, Frost M., 2021. Bone 143:115681.
Diffuse Idiopathic Skeletal Hyperostosis (DISH) in Type 2 Diabetes: A New Imaging Possibility and a New Biomarker. Fassio, A., Adami G., Idolazzi L., Giollo A., Viapiana O., Bosco E., Negrelli R., Sani E., Sandri D., Mantovani A., Targher G., Rossini M., Gatti D., 2021. Calcified Tissue Int 108(2): 231–39.
Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism. Turner ME., White CA., Taylor SM., Neville K., Rees-Milton K., Hopman WM., Adams MA., Anastassiades T., Holden RM., 2021. Calcif Tissue Int 108(3):354-363.
Sclerostin measurement in human disease: Validity and current limitations.
Costa, A.G., Cremers, S., Bilezikian, J.P., 2017. Bone 96, 24–28.
PMID: 27742501
Hormonal and systemic regulation of sclerostin.
Drake, M.T., Khosla, S., 2017. Bone 96, 8–17.
Clinical utility of anti-sclerostin antibodies.
McClung, M.R., 2017. Bone 96, 3–7.PMID: 28115281
Renal elimination of sclerostin increases with declining kidney function.
Cejka, D., Marculescu, R., Kozakowski, N., Plischke, M., Reiter, T., Gessl, A., Haas, M., 2014. J. Clin. Endocrinol. Metab. 99, 248–255.PMID: 24187403
New insights into the location and form of sclerostin.
Hernandez, P., Whitty, C., John Wardale, R., Henson, F.M.D., 2014. Biochem. Biophys. Res. Commun. 446, 1108–1113.PMID: 24667598
Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients.
Kanbay, M., Siriopol, D., Saglam, M., Kurt, Y.G., Gok, M., Cetinkaya, H., Karaman, M., Unal, H.U., Oguz, Y., Sari, S., Eyileten, T., Goldsmith, D., Vural, A., Veisa, G., Covic, A., Yilmaz, M.I., 2014. J. Clin. Endocrinol. Metab. 99, E1854-1861.PMID: 25057883
Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis.
Malluche, H.H., Davenport, D.L., Cantor, T., Monier-Faugere, M.-C., 2014. Clinical Journal of the American Society of Nephrology 9, 1254–1262.
The osteocyte: an endocrine cell ... and more.
Dallas, S.L., Prideaux, M., Bonewald, L.F., 2013. Endocr. Rev. 34, 658–690.PMID: 23612223; PMCID: PMC3785641
Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study.
Garnero, P., Sornay-Rendu, E., Munoz, F., Borel, O., Chapurlat, R.D., 2013. Osteoporos Int 24, 489–494.PMID: 22525978
The relation between renal function and serum sclerostin in adult patients with CKD.
Pelletier, S., Dubourg, L., Carlier, M.-C., Hadj-Aissa, A., Fouque, D., 2013. Clin J Am Soc Nephrol 8, 819–823.PMID: 23430206; PMCID: PMC3641616
Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis?
Viaene, L., Behets, G.J., Claes, K., Meijers, B., Blocki, F., Brandenburg, V., Evenepoel, P., D’Haese, P.C., 2013. Nephrol. Dial. Transplant. 28, 3024–3030.PMID: 23605174
Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults.
Amrein, K., Amrein, S., Drexler, C., Dimai, H.P., Dobnig, H., Pfeifer, K., Tomaschitz, A., Pieber, T.R., Fahrleitner-Pammer, A., 2012. J. Clin. Endocrinol. Metab. 97, 148–154.PMID: 21994959
Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients.
Cejka, D., Jager-Lansky, A., Kieweg, H., Weber, M., Bieglmayer, C., Haider, D.G., Diarra, D., Patsch, J.M., Kainberger, F., Bohle, B., Haas, M., 2012. Nephrology Dialysis Transplantation 27, 226–230.
Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy.
Terpos, E., Christoulas, D., Katodritou, E., Bratengeier, C., Gkotzamanidou, M., Michalis, E., Delimpasi, S., Pouli, A., Meletis, J., Kastritis, E., Zervas, K., Dimopoulos, M.A., 2012. Int. J. Cancer 131, 1466–1471.PMID: 22052418
Serum sclerostin levels in Paget’s disease and prostate cancer with bone metastases with a wide range of bone turnover.
Yavropoulou, M.P., van Lierop, A.H., Hamdy, N.A.T., Rizzoli, R., Papapoulos, S.E., 2012. Bone 51, 153–157.PMID: 22579776
Circulating Sclerostin in Disorders of Parathyroid Gland Function.
Costa, A.G., Cremers, S., Rubin, M.R., McMahon, D.J., Sliney, J., Lazaretti-Castro, M., Silverberg, S.J., Bilezikian, J.P., 2011. J Clin Endocrinol Metab 96, 3804–3810.PMID: 21937621; PMCID: PMC3232608
Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls.
Lierop, A.H. van, Witteveen, J.E., Hamdy, N. a. T., Papapoulos, S.E., 2010. European Journal of Endocrinology 163, 833–837.
Sclerostin in mineralized matrices and van Buchem disease.
van Bezooijen, R.L., Bronckers, A.L., Gortzak, R.A., Hogendoorn, P.C.W., van der Wee-Pals, L., Balemans, W., Oostenbroek, H.J., Van Hul, W., Hamersma, H., Dikkers, F.G., Hamdy, N. a. T., Papapoulos, S.E., Löwik, C.W.G.M., 2009. J. Dent. Res. 88, 569–574.PMID: 19587164
Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin.
Robling, A.G., Niziolek, P.J., Baldridge, L.A., Condon, K.W., Allen, M.R., Alam, I., Mantila, S.M., Gluhak-Heinrich, J., Bellido, T.M., Harris, S.E., Turner, C.H., 2008. J. Biol. Chem. 283, 5866–5875.PMID: 18089564
Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal.
Wergedal, J.E., Veskovic, K., Hellan, M., Nyght, C., Balemans, W., Libanati, C., Vanhoenacker, F.M., Tan, J., Baylink, D.J., Van Hul, W., 2003. J. Clin. Endocrinol. Metab. 88, 5778–5783.PMID: 14671168
From skeletal to cardiovascular disease in 12 steps—the evolution of sclerostin as a major player in CKD-MBD.
Brandenburg, V.M., D’Haese, P., Deck, A., Mekahli, D., Meijers, B., Neven, E., Evenepoel, P., 2016. Pediatric Nephrology 31, 195–206.
Sclerostin and DKK1: new players in renal bone and vascular disease.
Evenepoel, P., D’Haese, P., Brandenburg, V., 2015. Kidney International 88, 235–240.
Sclerostin and its significance for children and adolescents with type 1 diabetes mellitus (T1D).
Wędrychowicz, A., Sztefko, K., Starzyk, J.B., 2018. Bone 120, 387-392.PMID: 30120991
Biochemical bone turnover markers in diabetes mellitus - A systematic review.
Starup-Linde, J., Vestergaard, P., 2016. Bone 82, 69–78.PMID: 25722065
All Biomedica ELISAs are validated according to international FDA/ICH/EMEA guidelines. For more information about our validation guidelines, please refer to our quality page and published validation guidelines and literature.
- ICH Q2(R1) Validation of Analytical Procedures: Text and Methodology.
- EMEA/CHMP/EWP/192217/2009 Guideline on bioanalytical method validation.
- Bioanalytical Method Validation, Guidance for Industry, FDA, May 2018
Calibration
The Sclerostin ELISA immunoassay is calibrated against recombinant human Sclerostin protein (Q9BQB4 (Uniprot ID)).
Sclerostin ELISA Detection Limit & Sensitivity
To determine the sensitivity of the Sclerostin ELISA, experiments measuring the lower limit of detection (LOD) and the lower limit of quantification (LLOQ) were conducted.
The LOD, also called the detection limit, is the lowest point at which a signal can be distinguished above the background signal, i.e. the signal that is measured in the absence of Sclerostin, with a confidence level of 99%. It is defined as the mean back calculated concentration of standard 1 (0 pmol/l of Sclerostin, five independent measurements) plus three times the standard deviation of the measurements.
The LLOQ, or sensitivity of an assay, is the lowest concentration at which an analyte can be accurately quantified. The criteria for accurate quantification at the LLOQ are an analyte recovery between 75 and 125% and a coefficient of variation (CV) of less than 25%. To determine the LLOQ, standard 2, i.e. the lowest standard containing Sclerostin, is diluted, measured five times and its concentration is back calculated. The lowest dilution, which meets both criteria, is reported as the LLOQ.
The following values were determined for the Sclerostin ELISA:
|
LOD |
3.2 pmol/l |
|
LLOQ |
7.5 pmol/l |
Sclerostin ELISA Precision
The precision of an ELISA is defined as its ability to measure the same concentration consistently within the same experiments carried out by one operator (within-run precision or repeatability) and across several experiments using the same samples but conducted by several operators using different ELISA lots (in-between-run precision or reproducibility).
Within-Run Precision
Within-run (intra-assay) precision was assessed by measuring two samples of known concentrations eight times within one Sclerostin ELISA kit lot by one operator.
|
ID |
n |
Mean Sclerostin [pmol/l] |
SD [pmol/l] |
CV (%) |
|
Sample 1 |
8 |
33.6 |
2.37 |
7 |
|
Sample 2 |
8 |
118.8 |
5.36 |
5 |
In-Between-Run Precision
In-between-run (inter-assay) precision was assessed by measuring two samples six times within three ELISA kit lots by two different operators.
|
ID |
n |
Mean Sclerostin [pmol/l] |
SD [pmol/l] |
CV (%) |
|
Sample 1 |
6 |
30.5 |
3.19 |
10 |
|
Sample 2 |
6 |
120.2 |
3.67 |
3 |
Sclerostin ELISA Accuracy
The accuracy of an ELISA is defined as the precision with which it can recover samples of known concentrations.
The recovery of the Sclerostin ELISA was measured by adding recombinant Sclerostin to human samples containing a known concentration endogenous bioactive Sclerostin. The % recovery of the spiked concentration was calculated as the percentage of measured compared over the expected value.
The table shows the summary of the recovery experiments in the Sclerostin ELISA in human serum samples:
|
% Recovery |
|||||
|
+70 pmol/l |
+120 pmol/l |
||||
|
Sample matrix |
n |
Mean |
Range |
Mean |
Range |
|
Serum |
6 |
97 |
93-101 |
90 |
84-97 |
Data showing % recovery of recombinant Sclerostin in human serum samples:
|
Sclerostin [pmol/l] |
% Recovery |
|||||
|
Sample matrix |
ID |
Reference |
+ 70 pmol/l |
+ 120 pmol/l |
+ 70 pmol/l |
+ 120 pmol/l |
|
Serum |
s1 |
25.1 |
73.4 |
126.7 |
101 |
95 |
|
Serum |
s2 |
32.8 |
72.2 |
133.1 |
93 |
97 |
|
Serum |
s3 |
29.3 |
72.4 |
115.3 |
96 |
84 |
|
Serum |
s4 |
33.2 |
76.1 |
123.4 |
99 |
89 |
|
Serum |
s5 |
28.5 |
70.0 |
119.0 |
93 |
87 |
|
Serum |
s6 |
31.3 |
75.1 |
117.3 |
99 |
85 |
|
Mean |
97 |
90 |
||||
|
Min |
93 |
84 |
||||
|
Max |
101 |
97 |
||||
Sclerostin ELISA Dilution Linearity & Parallelism
Tests of dilution linearity and parallelism ensure that both endogenous and recombinant samples containing Sclerostin behave in a dose dependent manner and are not affected by matrix effects. Dilution linearity assesses the accuracy of measurements in diluted clinical samples spiked with known concentrations of recombinant analyte. By contrast, parallelism refers to dilution linearity in clinical samples and provides evidence that the endogenous analyte behaves in same way as the recombinant one. Dilution linearity and parallelism are assessed for each sample type and are considered acceptable if the results are within ± 20% of the expected concentration.
Dilution Linearity
Dilution linearity was assessed by serially diluting human samples spiked with 100 pmol/l recombinant Sclerostin with assay buffer.
The table below shows the mean recovery and range of serially diluted recombinant Sclerostin in serum:
|
% Recovery of recombinant Sclerostin in diluted samples |
|||||
|
1+1 |
1+3 |
||||
|
Sample matrix |
n |
Mean |
Range |
Mean |
Range |
|
Serum |
3 |
96 |
94-100 |
108 |
100-113 |
Data showing dilution linearity of human serum samples containing recombinant Sclerostin:
|
Sclerostin [pmol/l] |
% Recovery |
||||||
|
Sample matrix |
ID |
Unspiked |
Reference |
1+1 |
1+3 |
1+1 |
1+3 |
|
Serum |
s1 |
10.0 |
99.5 |
51.6 |
22.5 |
96 |
111 |
|
Serum |
s2 |
10.2 |
96.1 |
51.1 |
24.0 |
94 |
100 |
|
Serum |
s3 |
7.9 |
85.8 |
42.7 |
19.0 |
100 |
113 |
|
|
Mean |
96 |
108 |
||||
|
|
Min |
94 |
100 |
||||
|
Max |
100 |
113 |
|||||
Parallelism
Parallelism was assessed by serially diluting serum samples containing endogenous Sclerostin with assay buffer.
The table below shows the mean recovery and range of serially diluted endogenous Sclerostin in human serum:
| % Recovery of endogenous Sclerostin in diluted samples | |||||||
|
1+1 |
1+3 |
1+7 |
|||||
|
Sample matrix |
n |
Mean |
Range |
Mean |
Range |
Mean |
Range |
|
Serum |
4 |
110 |
96-121 |
113 |
99-130 |
106 |
72-139 |
Data showing dilution linearity of human serum samples containing endogenous Sclerostin:
|
Sclerostin [pmol/l] |
% Recovery |
|||||||
|
Sample matrix |
ID |
Reference |
1+1 |
1+3 |
1+7 |
1+1 |
1+3 |
1+7 |
|
Serum |
s1 |
176 |
106 |
57 |
31 |
121 |
130 |
139 |
|
Serum |
s2 |
75 |
36 |
19 |
7 |
96 |
99 |
72 |
|
Serum |
s3 |
50 |
27 |
13 |
6 |
108 |
102 |
93 |
|
Serum |
s4 |
242 |
142 |
74 |
36 |
117 |
122 |
119 |
|
|
Mean |
110 |
113 |
106 |
||||
|
|
Min |
96 |
99 |
72 |
||||
|
|
Max |
121 |
130 |
139 |
||||
Sclerostin ELISA Specificity
The specificity of an ELISA is defined as its ability to exclusively recognize the analyte of interest.
The specificity of the Sclerostin ELISA was shown by characterizing both the capture and the detection antibodies through epitope mapping.
Epitope Mapping
Linear epitopes of both utilized antibodies were analyzed with a microarray technique of overlapping peptides spotted to a glass slide. Linear epitopes of the polyclonal capture antibody are distributed throughout the whole Sclerostin protein, whereas the monoclonal detection antibody has just one epitope in the core region.
Cross Reactivity
The cross-reactivity of the Sclerostin ELISA was tested on a panel of related molecules. The Sclerostin ELISA does not recognize Noggin and Wise (SOSTDC1).
The assay does not detect rat or mouse Sclerostin.
Sample Stability
The stability of endogenous Sclerostin was tested by comparing Sclerostin measurements in serum samples that had undergone four freeze-thaw cycles. Samples can undergo at least four freeze-thaw cycles.
The mean CV of human serum samples (n=4) containing different levels of endogenous Sclerostin after four freeze-thaw cycles is 3%.
Sample Values
Sclerostin Values in Apparently Healthy Individuals
To provide expected values for circulating Sclerostin, a panel of samples from apparently healthy donors was tested.
A summary of the results is shown below:
|
Sample matrix |
n |
Median |
5% Percentile |
95% Percentile |
|
Serum |
411 |
24.14 |
10.78 |
52.02 |
|
Citrate plasma |
40 |
33 |
20 |
54 |
It is recommended to establish the normal range for each laboratory.
Sclerostin Values from Donor Sera of an Unselected Hospital Panel
A panel of samples from an unselected hospital panel was tested.
A summary of the results is shown below:
|
Sample matrix |
n |
Median |
5% Percentile |
95% Percentile |
|
Serum |
15 |
57 |
9 |
118 |
|
Citrate plasma |
40 |
33 |
20 |
54 |
Matrix Comparison
To assess whether all tested matrices behave the same way in the Sclerostin ELISA, concentrations of Sclerostin were measured in serum, EDTA, heparın and citrate plasma samples prepared from eight apparently healthy donors. Each individual donated blood in all tested sample matrices.
A summary table of Sclerostin levels in various sample matrices is shown below:
|
Sclerostin [pmol/l] |
|||||
|
Sample ID |
Serum |
EDTA plasma |
Citrate plasma |
Heparın plasma |
% CV |
|
#1 |
26.4 |
20.0 |
23.2 |
25.4 |
12 |
|
#2 |
22.4 |
16.3 |
19.6 |
19.8 |
13 |
|
#3 |
26.9 |
18.8 |
23.6 |
22.9 |
15 |
|
#4 |
17.1 |
12.1 |
14.2 |
14.6 |
14 |
|
#5 |
28.3 |
22.7 |
26.4 |
26.8 |
9 |
|
#6 |
28.2 |
21.9 |
29.1 |
31.5 |
15 |
|
#7 |
27.9 |
22.0 |
25.4 |
26.0 |
10 |
|
#8 |
18.5 |
11.6 |
13.5 |
16.7 |
20 |
|
|
Mean |
13 |
|||
Comparison with other Assays
Biomedica’s Sclerostin ELISA (Cat. No. BI-20492*) was compared with the bioactive Sclerostin ELISA (Cat. No. BI-20472**). The same panel of samples was tested (16 EDTA plasma samples and 16 serum samples). The correlation between the two assays was R= 0.58.
*launched 2013, ** launched 2018
The correlation between the two assays resulted in R2=0.58. Sclerostin sample values measured with the Biomedica “bioactive Sclerostin ELISA” (Cat. No. BI-20472) are higher than in the Biomedica “Sclerostin ELISA” (Cat. No. BI-20492). The results demonstrate that the antibodies utilized in both assays bind to different regions of the Sclerostin molecule. The monoclonal capture antibody of the bioactive Sclerostin ELISA binds to the receptor binding site of Sclerostin, a region that is most probably more resistant to cleavage.
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PMID:30910600 - Secukinumab produces a quick increase in WNT signalling antagonists in patients with psoriatic arthritis.
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PMID:30418122 - A rare SMAD9 mutation identifies the BMP signalling pathway as a potential osteoanabolic target.
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Ikeda, T., Kaji, H., Tamura, Y., Akagi, M., 2019. J Orthop Sci 24, 532–538.
PMID:30573396 - Sclerostin levels predict cardiovascular mortality in long-term hemodialysis patients: a prospective observational cohort study.
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PMID:31177791 - Relationship between serum sclerostin, vascular sclerostin expression and vascular calcification assessed by different methods in ESRD patients eligible for renal transplantation: a cross-sectional study.
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PMID:30515734 - Serum bone markers in ROD patients across the spectrum of decreases in GFR: Activin A increases before all other markers.
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PMID:30862350; PMCID: PMC6595397 - Serum sclerostin as a potential biomarker of vascular and valvular types of calcification in chronic kidney disease cases with and without maintenance hemodialysis.
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PMID:30640713; PMCID: PMC6330718 - Sclerostin and its association with insulin resistance in children and adolescents.
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PMID:30116403; PMCID: PMC6079590 - Sclerostin and its significance for children and adolescents with type 1 diabetes mellitus (T1D).
Wędrychowicz, A., Sztefko, K., Starzyk, J.B., 2019. Bone 120, 387–392.
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PMID:30227689; PMCID: PMC6162798 - Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes.
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PMID:29343193 - Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.
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PMID:29198074 - Pulsed electromagnetic fields modulate bone metabolism via RANKL/OPG and Wnt/β-catenin pathways in women with postmenopausal osteoporosis: A pilot study.
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PMID:30482161 - Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis.
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PMID:30314461; PMCID: PMC6186107 - Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators.
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PMID:30599401 - Bone Geometry, Quality, and Bone Markers in Children with Type 1 Diabetes Mellitus.
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PMID:29356934 - Effect of Teri paratide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.
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PMID:29999549 - Bone metabolism in patients with anorexia nervosa and amenorrhoea.
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Ikeda, T., Kaji, H., Tamura, Y., Akagi, M., 2018. Journal of Orthopaedic Science.
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PMID:29383454 - Glucocorticoid therapy causes contradictory changes of serum Wnt signaling-related molecules in systemic autoimmune diseases.
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PMID:30171335 - Myostatin and other musculoskeletal markers in lung transplant recipients.
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PMID:30317402 - Relationship between serum sclerostin, vascular sclerostin expression and vascular calcification assessed by different methods in ESRD patients eligible for renal transplantation: a cross-sectional study.
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PMID:30515734 - The serum sclerostin level is positively associated with the aortic augmentation index in patients on peritoneal dialysis.
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PMID:30315891 - Serum Sclerostin and Bone Turnover in Latent Autoimmune Diabetes in Adults.
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PMID:29506222 - Association Between Risk Factors Including Bone-Derived Biomarkers and Aortic Arch Calcification in Maintenance Hemodialysis Patients.
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PMID:30347400 - Circulating levels of sclerostin are associated with cardiovascular mortality.
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PMID:29928063; PMCID: PMC6013204 - Bone metabolic responses to low energy availability achieved by diet or exercise in active eumenorrheic women.
Papageorgiou, M., Martin, D., Colgan, H., Cooper, S., Greeves, J.P., Tang, J.C.Y., Fraser, W.D., Elliott-Sale, K.J., Sale, C., 2018. Bone 114, 181–188.
PMID:29933113 - Glycemic Control and Bone Turnover in Older Mexican Americans with Type 2 Diabetes.
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PMID:29862008; PMCID: PMC5971242 - A Prospective Cohort Study Showing No Association Between Serum Sclerostin Level and Mortality in Maintenance Hemodialysis Patients.
Sato, M., Hanafusa, N., Kawaguchi, H., Tsuchiya, K., Nitta, K., 2018. Kidney and Blood Pressure Research 43, 1023–1033.
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PMID:30443790 - Consolidation therapy with the combination of borte zomib and lena lidomide (VR) without dexa methasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates.
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PMID:30592079 - Serum sclerostin concentration reflects bone turnover and glycation in men with type 2 diabetes mellitus.
Tomatsu, E., Shibata, M., Yoshino, Y., Sekiguchi-Ueda, S., Kakita, A., Takayanagi, T., Makino, M., Hayakawa, N., Suzuki, A., 2018. FMJ 4, 1–5.
- Deno sumab effects on bone density and turnover in postmenopausal women with low bone mass with or without previous treatment.
Tsourdi, E., Makras, P., Rachner, T.D., Polyzos, S., Rauner, M., Mandanas, S., Hofbauer, L.C., Anastasilakis, A.D., 2018. Bone 120, 44–49.
PMID:30292818 - Randomised study of children with obesity showed that whole body vibration reduced sclerostin.
Tubic, B., Zeijlon, R., Wennergren, G., Obermayer-Pietsch, B., Mårild, S., Dahlgren, J., Magnusson, P., Swolin-Eide, D., 2018. Acta Paediatr.
PMID:30071142 - Sclerostin and its significance for children and adolescents with type 1 diabetes mellitus (T1D).
Wędrychowicz, A., Sztefko, K., Starzyk, J.B., 2018. Bone.
PMID:30120991 - Changes in bone density and bone turnover in patients with rheumatoid arthritis treated with rituxi mab, results from an exploratory, prospective study.
Wheater, G., Elshahaly, M., Naraghi, K., Tuck, S.P., Datta, H.K., van Laar, J.M., 2018. PLoS ONE 13, e0201527.
PMID:30080871; PMCID: PMC6078302 - Correlation between sclerostin and Dickkopf-1 with aortic arterial stiffness in patients with type 2 diabetes: A prospective, cross-sectional study.
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PMID:30547685 - Genome-wide mapping identifies beta-1,4-N-acetyl-galactosaminyl-transferase as a novel determinant of sclerostin levels and bone mineral density.
Zheng, J., Maerz, W., Gergei, I., Kleber, M., Drechsler, C., Wanner, C., Brandenburg, V., Reppe, S., Gautvik, K., Medina-Gomez, C., Shevroja, E., Gilly, A., Park, Y.-C., Dedoussis, G., Zeggini, E., Lorentzon, M., Henning, P., Lerne, U., Nilsson, K., Moverare-Skrtic, S., Baird, D., Falk, L., Groom, A., Capellini, T., Grundberg, E., Nethander, M., Ohlsson, C., Smith, G.D., Tobias, J., 2018. bioRxiv 455386.
- Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1.
Zimmermann, A., Popp, R.A., Rossmann, H., Bucerzan, S., Nascu, I., Leucuta, D., Weber, M.M., Grigorescu-Sido, P., 2018. Therapeutics and Clinical Risk Management Volume 14, 2069–2080.
- Low periostin levels in adult patients with Langerhans cell histiocytosis are independently associated with the disease activity.
Anastasilakis, A.D., Polyzos, S.A., Tsoli, M., Papatheodorou, A., Kokkoris, P., Kaltsas, G., Terpos, E., Makras, P., 2017. Metabolism 71, 198–201.
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Behets, G.J., Viaene, L., Meijers, B., Blocki, F., Brandenburg, V.M., Verhulst, A., D’Haese, P.C., Evenepoel, P., 2017. PLOS ONE 12, e0176411.
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PMID:29263429; PMCID: PMC5738386 - Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis.
Carlson, N., Mortensen, O.H., Axelsen, M., Pedersen, R.S., Heaf, J.G., 2017. Blood Purif. 44, 122–128.
PMID:28554171 - Wnt antagonist sclerostin and Dickkopf-1 in gestational diabetes.
Catalano, A., Pintaudi, B., Morabito, N., Giunta, L., Loddo, S., Corrado, F., D’Anna, R., Lasco, A., Di Benedetto, A., 2017. Diabetes & Metabolism 43, 375–377.
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PMID:27742501 - Serum levels of Dickkopf-1 are a potential negative biomarker of survival in geriatric patients.
Dovjak, P., Heinze, G., Rainer, A., Sipos, W., Pietschmann, P., 2017. Experimental Gerontology 96, 104–109.
- In psoriatic arthritis Dkk-1 and PTH are lower than in rheumatoid arthritis and healthy controls.
Fassio, A., Idolazzi, L., Viapiana, O., Benini, C., Vantaggiato, E., Bertoldo, F., Rossini, M., Gatti, D., 2017. Clinical Rheumatology 36, 2377–2381.
- Adjuvant tam oxifen but not aromatase inhibitor therapy decreases serum levels of the Wnt inhibitor dickkopf-1 while not affecting sclerostin in breast cancer patients.
Göbel, A., Kuhlmann, J.D., Link, T., Wimberger, P., Browne, A.J., Rauner, M., Hofbauer, L.C., Rachner, T.D., 2017. Breast Cancer Research and Treatment 164, 737–743.
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Gruber, M., Gruber, R., Agis, H., 2017. Matters Archive.
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Idolazzi, L., Fassio, A., Tripi, G., Braga, V., Viapiana, O., Adami, G., Rossini, M., Gatti, D., 2017. Clinical Rheumatology 36, 925–928.
- Novel bone metabolism-associated hormones: the importance of the pre-analytical phase for understanding their physiological roles.
Lombardi, G., Barbaro, M., Locatelli, M., Banfi, G., 2017. Endocrine 56, 460–484.
- Long-Term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture.
Muschitz, G.K., Schwabegger, E., Fochtmann, A., Baierl, A., Kocijan, R., Haschka, J., Gruther, W., Schanda, J.E., Resch, H., Rath, T., Pietschmann, P., Muschitz, C., 2017. Journal of Bone and Mineral Research 32, 2381–2393.
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Perpétuo, I.P., Caetano-Lopes, J., Rodrigues, A.M., Campanilho-Marques, R., Ponte, C., Canhão, H., Ainola, M., Fonseca, J.E., 2017. BioMed Research International 2017, 1–10.
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Perpétuo, I.P., Caetano-Lopes, J., Vieira-Sousa, E., Campanilho-Marques, R., Ponte, C., Canhão, H., Ainola, M., Fonseca, J.E., 2017. Frontiers in Medicine 4.
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PMID:29263750; PMCID: PMC5726226 - Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation.
Tartaglione, L., Pasquali, M., Rotondi, S., Muci, M.L., Leonangeli, C., Farcomeni, A., Fassino, V., Mazzaferro, S., 2017. PLoS ONE 12, e0178637.
PMID:28558021; PMCID: PMC5448809 - Atypical skeletal manifestations of rickets in a familial hypocalciuric hypercalcemia patient.
Wu, B., Wang, O., Jiang, Y., Li, M., Xing, X., Xia, W., 2017. Bone Res 5, 17001.
PMID:28690912; PMCID: PMC5486235 - Serum Sclerostin Levels in Patients with Human Immunodeficiency Virus Infection and Their Association with Bone Turnover Markers and Bone Mineral Densitometry.
Almansouri, A.Y., Abdulfatah, M.E., Baaqil, O.H., Bakheet, A.A., Turki, S.A., Kotb, M.M., Althubaiti, A., Almaghrabi, M.M., Althubaiti, A.M., Madani, B.M., Jawad, A.S.M., 2016. J Bone Metab 23, 16–22.
PMID:26981516; PMCID: PMC4791433 - Presence of HLA-B27 is associated with changes of serum levels of mediators of the Wnt and hedgehog pathway.
Aschermann, S., Englbrecht, M., Bergua, A., Spriewald, B.M., Said-Nahal, R., Breban, M., Schett, G., Rech, J., 2016. Joint Bone Spine 83, 43–46.
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Briot, K., Etcheto, A., Miceli-Richard, C., Dougados, M., Roux, C., 2016. Rheumatology 55, 335–342.
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El-Bakry, S., Saber, N., Zidan, H., Samaha, D., 2016. The Egyptian Rheumatologist 38, 71–75.
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Faienza, M.F., Ventura, A., Delvecchio, M., Fusillo, A., Piacente, L., Aceto, G., Colaianni, G., Colucci, S., Cavallo, L., Grano, M., Brunetti, G., 2016. The Journal of Clinical Endocrinology & Metabolism jc.2016-2371.
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Fernández-Roldán, C., Genre, F., López-Mejías, R., Ubilla, B., Mijares, V., Cano, D.S., Robles, C.L., Callejas-Rubio, J.L., Fernández, R.R., Ruiz, M.E., González-Gay, M.Á., Centeno, N.O., 2016. BoneKEy Reports 5.
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Fujiwara, M., Kubota, T., Wang, W., Ohata, Y., Miura, K., Kitaoka, T., Okuzaki, D., Namba, N., Michigami, T., Kitabatake, Y., Ozono, K., 2016. Bone 85, 91–98.
- Direct effects of physical training on markers of bone metabolism and serum sclerostin concentrations in older adults with low bone mass.
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PMID:27278385; PMCID: PMC4899888 - Idiopathic Acquired Osteosclerosis in a Middle-Aged Woman With Systemic Lupus Erythematosus: IDIOPATHIC ACQUIRED OSTEOSCLEROSIS IN SLE.
Guañabens, N., Mumm, S., Gifre, L., Ruiz-Gaspà, S., Demertzis, J.L., Stolina, M., Novack, D.V., Whyte, M.P., 2016. Journal of Bone and Mineral Research 31, 1774–1782.
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Guañabens, N., Ruiz-Gaspà, S., Gifre, L., Miquel, R., Peris, P., Monegal, A., Dubrueil, M., Arias, A., Parés, A., 2016. Journal of Bone and Mineral Research 31, 1725–1733.
- Serum Sclerostin as an Independent Marker of Peripheral Arterial Stiffness in Renal Transplantation Recipients: A Cross-Sectional Study.
Hsu, B.-G., Liou, H.-H., Lee, C.-J., Chen, Y.-C., Ho, G.-J., Lee, M.-C., 2016. Medicine 95, e3300
- Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine.
Kashii, M., Matuso, Y., Sugiura, T., Fujimori, T., Nagamoto, Y., Makino, T., Kaito, T., Ebina, K., Iwasaki, M., Yoshikawa, H., 2016. Journal of Bone and Mineral Metabolism 34, 315–324.
- Changes of serum sclerostin and Dickkopf-1 levels during the menstrual cycle. A pilot study.
Liakou, C.G., Mastorakos, G., Makris, K., Fatouros, I.G., Avloniti, A., Marketos, H., Antoniou, J.D., Galanos, A., Dontas, I., Rizos, D., Tournis, S., 2016. Endocrine 54, 543–551.
PMID:27601021 - Validation of commercially available ELISAs for the detection of circulating sclerostin in hemodialysis patients.
Mause, S.F., Deck, A., Hennies, M., Kaesler, N., Evenepoel, P., Boisvert, W.A., Janssen, U., Brandenburg, V.M., 2016. Discoveries (Craiova) 4, e55.
PMID:27088126; PMCID: PMC4829955 - Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.
Morabito, N., Catalano, A., Gaudio, A., Morini, E., Bruno, L.M., Basile, G., Tsiantouli, E., Bellone, F., Agostino, R.M., Piraino, B., La Rosa, M.A., Salpietro, C., Lasco, A., 2016. Journal of Bone and Mineral Metabolism 34, 540–546.
- The Impact of Vitamin D, Calcium, Protein Supplementation, and Physical Exercise on Bone Metabolism After Bariatric Surgery: The BABS Study: BONE METABOLISM AFTER BARIATRIC SURGERY (BABS).
Muschitz, C., Kocijan, R., Haschka, J., Zendeli, A., Pirker, T., Geiger, C., Müller, A., Tschinder, B., Kocijan, A., Marterer, C., Nia, A., Muschitz, G.K., Resch, H., Pietschmann, P., 2016. Journal of Bone and Mineral Research 31, 672–682.
- How Accurate is Your Sclerostin Measurement? Comparison Between Three Commercially Available Sclerostin ELISA Kits.
Piec, I., Washbourne, C., Tang, J., Fisher, E., Greeves, J., Jackson, S., Fraser, W.D., 2016. Calcif. Tissue Int. 98, 546–555.
PMID:26749312; PMCID: PMC4860200 - Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease.
Polyzos, S.A., Anastasilakis, A.D., Kountouras, J., Makras, P., Papatheodorou, A., Kokkoris, P., Sakellariou, G.T., Terpos, E., 2016. Journal of Bone and Mineral Metabolism 34, 447–456.
- Higher Level of Dickkopf-1 is Associated with Low Bone Mineral Density and Higher Prevalence of Vertebral Fractures in Patients with Ankylosing Spondylitis.
Rossini, M., Viapiana, O., Idolazzi, L., Ghellere, F., Fracassi, E., Troplini, S., Povino, M.R., Kunnathully, V., Adami, S., Gatti, D., 2016. Calcified Tissue International 98, 438–445.
- Increased Dickkopf-1 in Recent-onset Rheumatoid Arthritis is a New Biomarker of Structural Severity. Data from the ESPOIR Cohort.
Seror, R., Boudaoud, S., Pavy, S., Nocturne, G., Schaeverbeke, T., Saraux, A., Chanson, P., Gottenberg, J.-E., Devauchelle-Pensec, V., Tobón, G.J., Mariette, X., Miceli-Richard, C., 2016. Scientific Reports 6.
- Differences in biochemical bone markers by diabetes type and the impact of glucose.
Starup-Linde, J., Lykkeboe, S., Gregersen, S., Hauge, E.-M., Langdahl, B.L., Handberg, A., Vestergaard, P., 2016. Bone 83, 149–155.
PMID:26555635 - Serum sclerostin levels in renal cell carcinoma patients with bone metastases.
Wibmer, C., Amrein, K., Fahrleitner-Pammer, A., Gilg, M.M., Berghold, A., Hutterer, G.C., Maurer-Ertl, W., Gerger, A., Leithner, A., Pichler, M., Szkandera, J., 2016. Scientific Reports 6.
- Sclerostin as a novel marker of bone turnover in athletes.
Zagrodna, A., Jóźków, P., Mędraś, M., Majda, M., Słowińska-Lisowska, M., 2016. Biol Sport 33, 83–87.
PMID:26929475; PMCID: PMC4763547 - Deno sumab versus zole dronic acid in patients previously treated with zole dronic acid.
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PMID:25990355 - Sclerostin and Insul in 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., 2015. Diabetes Care 38, 1509–1517.
PMID:26084344 - Effects of Age and Estrogen on Skeletal Gene Expression in Humans as Assessed by RNA Sequencing.
Farr, J.N., Roforth, M.M., Fujita, K., Nicks, K.M., Cunningham, J.M., Atkinson, E.J., Therneau, T.M., McCready, L.K., Peterson, J.M., Drake, M.T., Monroe, D.G., Khosla, S., 2015. PLoS ONE 10, e0138347.
PMID:26402159; PMCID: PMC4581624 - Strong relationship between vitamin D status and bone mineral density in anorexia nervosa.
Gatti, D., El Ghoch, M., Viapiana, O., Ruocco, A., Chignola, E., Rossini, M., Giollo, A., Idolazzi, L., Adami, S., Dalle Grave, R., 2015. Bone 78, 212–215
- Effect of Recent Spinal Cord Injury on Wnt Signaling Antagonists (Sclerostin and Dkk-1) and Their Relationship With Bone Loss. A 12-Month Prospective Study: RECENT SCI AND BONE LOSS.
Gifre, L., Vidal, J., Carrasco, J.L., Filella, X., Ruiz-Gaspà, S., Muxi, A., Portell, E., Monegal, A., Guañabens, N., Peris, P., 2015. Journal of Bone and Mineral Research 30, 1014–1021.
- Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race.
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- Increased sclerostin levels after further ablation of remnant estrogen by aromatase inhibitors.
Kim, W., Chung, Y., Kim, S.H., Park, S., Bae, J.H., Kim, G., Lee, S.J., Kim, J.E., Park, B.W., Lim, S.K., Rhee, Y., 2015. Endocrinol Metab (Seoul) 30, 58–64.
PMID:25827459; PMCID: PMC4384667 - Association of circulating sclerostin with vascular calcification in Afro-Caribbean men.
Kuipers, A.L., Miljkovic, I., Carr, J.J., Terry, J.G., Nestlerode, C.S., Ge, Y., Bunker, C.H., Patrick, A.L., Zmuda, J.M., 2015. Atherosclerosis 239, 218–223.
PMID:25618029; PMCID: PMC4331206 - Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths.
Mora, S., Puzzovio, M., Giacomet, V., Fabiano, V., Maruca, K., Capelli, S., Nannini, P., Lombardi, G., Zuccotti, G.V., 2015. Endocrine 49, 783–790.
- Sclerostin Levels and Changes in Bone Metabolism After Bariatric Surgery.
Muschitz, C., Kocijan, R., Marterer, C., Nia, A.R., Muschitz, G.K., Resch, H., Pietschmann, P., 2015. The Journal of Clinical Endocrinology & Metabolism 100, 891–901.
- Iban dronate Increases Sclerostin Levels and Bone Strength in Male Patients with Idiopathic Osteoporosis.
Muschitz, C., Kocijan, R., Pahr, D., Patsch, J.M., Amrein, K., Misof, B.M., Kaider, A., Resch, H., Pietschmann, P., 2015. Calcified Tissue International 96, 477–489.
- Switching from teno fovir to aba cavir in HIV-1-infected patients with low bone mineral density: changes in bone turnover markers and circulating sclerostin levels.
Negredo, E., Diez-Pérez, A., Bonjoch, A., Domingo, P., Pérez-Álvarez, N., Gutierrez, M., Mateo, G., Puig, J., Echeverría, P., Escrig, R., Clotet, B., 2015. J. Antimicrob. Chemother. 70, 2104–2107.
PMID:25769303 - Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort.
Nocturne, G., Pavy, S., Boudaoud, S., Seror, R., Goupille, P., Chanson, P., van der Heijde, D., van Gaalen, F., Berenbaum, F., Mariette, X., Briot, K., Feydy, A., Claudepierre, P., Dieudé, P., Nithitham, J., Taylor, K.E., Criswell, L.A., Dougados, M., Roux, C., Miceli-Richard, C., 2015. PLOS ONE 10, e0134974.
- Dickkopf-1 and sclerostin serum levels in patients with systemic mastocytosis.
Rossini, M., Viapiana, O., Zanotti, R., Tripi, G., Perbellini, O., Idolazzi, L., Bonifacio, M., Adami, S., Gatti, D., 2015. Calcif. Tissue Int. 96, 410–416.
PMID:25694360 - Structural and functional insights into sclerostin-glycosaminoglycan interactions in bone.
Salbach-Hirsch, J., Samsonov, S.A., Hintze, V., Hofbauer, C., Picke, A.-K., Rauner, M., Gehrcke, J.-P., Moeller, S., Schnabelrauch, M., Scharnweber, D., Pisabarro, M.T., Hofbauer, L.C., 2015. Biomaterials 67, 335–345.
PMID:26232882 - Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone.
Skowrońska-Jóźwiak, E., Lewandowski, K.C., Adamczewski, Z., Krawczyk-Rusiecka, K., Lewiński, A., 2015. Int J Endocrinol 2015, 948384.
PMID:26366174; PMCID: PMC4561097 - Bone metabolism and renal stone risk during International Space Station missions.
Smith, S.M., Heer, M., Shackelford, L.C., Sibonga, J.D., Spatz, J., Pietrzyk, R.A., Hudson, E.K., Zwart, S.R., 2015. Bone 81, 712–720.
PMID:26456109 - 1α,25-dihydroxyvitamin D3 stimulates human SOST gene expression and sclerostin secretion.
Wijenayaka, A.R., Yang, D., Prideaux, M., Ito, N., Kogawa, M., Anderson, P.H., Morris, H.A., Solomon, L.B., Loots, G.G., Findlay, D.M., Atkins, G.J., 2015. Mol. Cell. Endocrinol. 413, 157–167.
PMID:26112182 - Factors associated with serum soluble inhibitors of Wnt-β-catenin signaling (sclerostin and dickkopf-1) in patients undergoing peritoneal dialysis: Soluble Wnt-β-catenin inhibitors in PD.
Yamada, S., Tsuruya, K., Tokumoto, M., Yoshida, H., Ooboshi, H., Kitazono, T., 2015. Nephrology 20, 639–645.
- Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus.
Catalano, A., Pintaudi, B., Morabito, N., Di Vieste, G., Giunta, L., Bruno, M.L., Cucinotta, D., Lasco, A., Di Benedetto, A., 2014. Eur. J. Endocrinol. 171, 293–300.
PMID:24891138 - Renal elimination of sclerostin increases with declining kidney function.
Cejka, D., Marculescu, R., Kozakowski, N., Plischke, M., Reiter, T., Gessl, A., Haas, M., 2014. J. Clin. Endocrinol. Metab. 99, 248–255.
PMID:24187403 - Serum Levels of Sclerostin and Dickkopf-1: Effects of Age, Gender and Fracture Status.
Dovjak, P., Dorfer, S., Föger-Samwald, U., Kudlacek, S., Marculescu, R., Pietschmann, P., 2014. Gerontology 60, 493–501.
- The Effect of Leptin Replacement on Parathyroid Hormone, RANKL-Osteoprotegerin Axis, and Wnt Inhibitors in Young Women With Hypothalamic Amenorrhea.
Foo, J.-P., Polyzos, S.A., Anastasilakis, A.D., Chou, S., Mantzoros, C.S., 2014. The Journal of Clinical Endocrinology & Metabolism 99, E2252–E2258.
- Distinct effect of zoledronate and clo dronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis.
Gatti, D., Viapiana, O., Idolazzi, L., Fracassi, E., Ionescu, C., Dartizio, C., Troplini, S., Kunnathully, V., Adami, S., Rossini, M., 2014. Bone 67, 189–192.
- The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus.
Gaudio, A., Privitera, F., Pulvirenti, I., Canzonieri, E., Rapisarda, R., Fiore, C.E., 2014. Diabetes and Vascular Disease Research 11, 48–52.
- Serum sclerostin in hepatitis C virus infected patients.
González-Reimers, E., López-Prieto, J., Pelazas-González, R., Alemán-Valls, M.R., José de la Vega-Prieto, M., Jorge-Ripper, C., Durán-Castellón, M.C., Santolaria-Fernández, F., 2014. J Bone Metab 21, 69–75.
PMID:24707469; PMCID: PMC3970296 - Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients.
Kanbay, M., Siriopol, D., Saglam, M., Kurt, Y.G., Gok, M., Cetinkaya, H., Karaman, M., Unal, H.U., Oguz, Y., Sari, S., Eyileten, T., Goldsmith, D., Vural, A., Veisa, G., Covic, A., Yilmaz, M.I., 2014. J. Clin. Endocrinol. Metab. 99, E1854-1861.
PMID:25057883 - The effect of renal dysfunction on circulating sclerostin level in patients with type 2 diabetes.
Kim, S.H., Yoon, S.Y., Lim, S.-K., Rhee, Y., 2014. Int J Endocrinol 2014, 715908.
PMID:25053944; PMCID: PMC4099222 - Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes.
Klangjareonchai, T., Nimitphong, H., Saetung, S., Bhirommuang, N., Samittarucksa, R., Chanprasertyothin, S., Sudatip, R., Ongphiphadhanakul, B., 2014. Int J Endocrinol 2014, 261545.
PMID:25276128; PMCID: PMC416781 - Biomarkers of Bone Metabolism in Ankylosing Spondylitis in Relation to Osteoproliferation and Osteoporosis.
Klingberg, E., Nurkkala, M., Carlsten, H., Forsblad-d’Elia, H., 2014. The Journal of Rheumatology 41, 1349–1356.
- Relative influence of heritability, environment and genetics on serum sclerostin.
Kuipers, A.L., Zhang, Y., Yu, S., Kammerer, C.M., Nestlerode, C.S., Chu, Y., Bunker, C.H., Patrick, A.L., Wheeler, V.W., Miljkovic, I., Zmuda, J.M., 2014. Osteoporos Int 25, 905–912.
PMID:24136102; PMCID: PMC3948173 - Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer.
Kyvernitakis, I., Rachner, T.D., Urbschat, A., Hars, O., Hofbauer, L.C., Hadji, P., 2014. Journal of Cancer Research and Clinical Oncology 140, 1671–1680.
- Serum levels of sclerostin, Dickkopf-1, and secreted frizzled-related protein-4 are not changed in individuals with high bone mass causing mutations in LRP5.
Simpson, C.A., Foer, D., Lee, G.S., Bihuniak, J., Sun, B., Sullivan, R., Belsky, J., Insogna, K.L., 2014. Osteoporosis International 25, 2383–2388.
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Tuylu, T., Sari, I., Solmaz, D., Kozaci, D., Akar, S., Gunay, N., Onen, F., Akkoc, N., 2014. Clinics 69, 688–693.
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Anastasilakis, A.D., Polyzos, S.A., Gkiomisi, A., Bisbinas, I., Gerou, S., Makras, P., 2013. The Journal of Clinical Endocrinology & Metabolism 98, 3206–3212.
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Ardawi, M.-S.M., Akhbar, D.H., Alshaikh, A., Ahmed, M.M., Qari, M.H., Rouzi, A.A., Ali, A.Y., Abdulrafee, A.A., Saeda, M.Y., 2013. Bone 56, 355–362.
PMID:23845326 - Traditional and novel bone remodeling markers in premenopausal and postmenopausal women.
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PMID:24001743 - Zole dronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis.
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PMID:23596142 - Genetic studies on components of the Wnt signalling pathway and the severity of joint destruction in rheumatoid arthritis.
de Rooy, D.P.C., Yeremenko, N.G., Wilson, A.G., Knevel, R., Lindqvist, E., Saxne, T., Krabben, A., Leijsma, M.K., Daha, N.A., Tsonaka, S., Zhernakova, A., Houwing-Duistermaat, J.J., Huizinga, T.W.J., Toes, R.E.M., Baeten, D.L.P., Brouwer, E., van der Helm-van Mil, A.H.M., 2013. Annals of the Rheumatic Diseases 72, 769–775.
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Durosier, C., van Lierop, A., Ferrari, S., Chevalley, T., Papapoulos, S., Rizzoli, R., 2013. J Clin Endocrinol Metab. 98, 3873–3883.
PMID:23864703 - Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover.
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- Serum sclerostin in alcoholics: a pilot study.
González-Reimers, E., Martín-González, C., de la Vega-Prieto, M.J., Pelazas-González, R., Fernández-Rodríguez, C., López-Prieto, J., Alvisa-Negrín, J., Santolaria-Fernández, F., 2013. Alcohol 48, 278–282.
PMID:23296214 - Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels.
Morales-Santana, S., García-Fontana, B., García-Martín, A., Rozas-Moreno, P., García-Salcedo, J.A., Reyes-García, R., Muñoz-Torres, M., 2013. Diabetes Care 36, 1667–1674.
PMID:23288857; PMCID: PMC3661830 - The relation between renal function and serum sclerostin in adult patients with CKD.
Pelletier, S., Dubourg, L., Carlier, M.-C., Hadj-Aissa, A., Fouque, D., 2013. Clin J Am Soc Nephrol 8, 819–823.
PMID:23430206; PMCID: PMC3641616 - Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis?
Viaene, L., Behets, G.J., Claes, K., Meijers, B., Blocki, F., Brandenburg, V., Evenepoel, P., D’Haese, P.C., 2013. Nephrol. Dial. Transplant. 28, 3024–3030.
PMID:23605174 - Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus.
Yamamoto, M., Yamauchi, M., Sugimoto, T., 2013. J. Clin. Endocrinol. Metab. 98, 4030–4037.
PMID:23894157 - Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults.
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PMID:21994959 - Decreased serum sclerostin levels in patients with primary hyperparathyroidism: a cross-sectional and a longitudinal study.
Ardawi, M.-S. M., Al-Sibiany, A.M., Bakhsh, T.M., Rouzi, A.A., Qari, M.H., 2012. Osteoporos Int 23, 1789–1797.
PMID:22041864 - High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research Study.
Ardawi, Mohammed-Salleh M., Rouzi, A.A., Al-Sibiani, S.A., Al-Senani, N.S., Qari, M.H., Mousa, S.A., 2012. J. Bone Miner. Res. 27, 2592–2602.
PMID:22836717 - Physical activity in relation to serum sclerostin, insul in-like growth factor-1, and bone turnover markers in healthy premenopausal women: a cross-sectional and a longitudinal study.
Ardawi, Mohammed-Salleh M., Rouzi, A.A., Qari, M.H., 2012. J. Clin. Endocrinol. Metab. 97, 3691–3699.
PMID:22865898 - Physical training increases osteoprotegerin in postmenopausal women.
Bergström, I., Parini, P., Gustafsson, S.A., Andersson, G., Brinck, J., 2012. J. Bone Miner. Metab. 30, 202–207.
PMID:21823052 - Long-term treatment with ralo xifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women.
Chung, Y.E., Lee, S.H., Lee, S.-Y., Kim, S.-Y., Kim, H.-H., Mirza, F.S., Lee, S.-K., Lorenzo, J.A., Kim, G.S., Koh, J.-M., 2012. Osteoporos Int 23, 1235–1243.
PMID:21660558 - 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, J.A., Muñoz-Torres, M., 2012. J. Clin. Endocrinol. Metab. 97, 234–241.
PMID:22031520 - Sclerostin and DKK1 in postmenopausal osteoporosis treated with denosumab.
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- Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus.
Gaudio, A., Privitera, F., Battaglia, K., Torrisi, V., Sidoti, M.H., Pulvirenti, I., Canzonieri, E., Tringali, G., Fiore, C.E., 2012. The Journal of Clinical Endocrinology & Metabolism 97, 3744–3750.
- Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes.
Gennari, L., Merlotti, D., Valenti, R., Ceccarelli, E., Ruvio, M., Pietrini, M.G., Capodarca, C., Franci, M.B., Campagna, M.S., Calabrò, A., Cataldo, D., Stolakis, K., Dotta, F., Nuti, R., 2012. J. Clin. Endocrinol. Metab. 97, 1737–1744.
PMID:22399511 - Sclerostin levels during growth in children.
Kirmani, S., Amin, S., McCready, L.K., Atkinson, E.J., Melton, L.J., Müller, R., Khosla, S., 2012. Osteoporos Int 23, 1123–1130.
PMID:21617991; PMCID: PMC3606589 - Association between sclerostin and bone density in chronic spinal cord injury.
Morse, L.R., Sudhakar, S., Danilack, V., Tun, C., Lazzari, A., Gagnon, D.R., Garshick, E., Battaglino, R.A., 2012. J. Bone Miner. Res. 27, 352–359.
PMID:22006831; PMCID: PMC3288145 - Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women--the six-month effect of rise dronate and teriparatide.
Polyzos, S.A., Anastasilakis, A.D., Bratengeier, C., Woloszczuk, W., Papatheodorou, A., Terpos, E., 2012. Osteoporos Int 23, 1171–1176.
PMID:21305266 - Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?
Saad, C.G.S., Ribeiro, A.C.M., Moraes, J.C.B., Takayama, L., Goncalves, C.R., Rodrigues, M.B., de Oliveira, R.M., Silva, C.A., Bonfa, E., Pereira, R.M.R., 2012. Arthritis Res Ther 14, R216.
PMID:23062122; PMCID: PMC3580528 - Strongly enhanced levels of sclerostin during human fracture healing.
Sarahrudi, K., Thomas, A., Albrecht, C., Aharinejad, S., 2012. J. Orthop. Res. 30, 1549–1555.
PMID:22508529 - Serum sclerostin levels were positively correlated with fat mass and bone mineral density in central south Chinese postmenopausal women.
Sheng, Z., Tong, D., Ou, Y., Zhang, H., Zhang, Z., Li, S., Zhou, J., Zhang, J., Liao, E., 2012. Clin Endocrinol (Oxf) 76, 797–801.
PMID:22151063 - Successful treatment of thyrotoxicosis is accompanied by a decrease in serum sclerostin levels.
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