Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus
Context: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signal...
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Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2012-10, Vol.97 (10), p.3744-3750 |
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container_title | The journal of clinical endocrinology and metabolism |
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creator | Gaudio, Agostino Privitera, Filippo Battaglia, Katia Torrisi, Venerando Sidoti, Maria Helga Pulvirenti, Ivana Canzonieri, Elena Tringali, Giovanni Fiore, Carmelo Erio |
description | Context:
Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling.
Objectives:
The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers.
Design:
This was a cross-sectional study.
Setting and Patients:
The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay.
Results:
Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures.
Conclusions:
These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM. |
doi_str_mv | 10.1210/jc.2012-1901 |
format | Article |
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Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling.
Objectives:
The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers.
Design:
This was a cross-sectional study.
Setting and Patients:
The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay.
Results:
Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures.
Conclusions:
These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2012-1901</identifier><identifier>PMID: 22855334</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Aged ; beta Catenin - metabolism ; Biological and medical sciences ; Biomarkers - metabolism ; Bone Density - physiology ; Bone Morphogenetic Proteins - blood ; Bone Remodeling - physiology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic Markers ; Humans ; Medical sciences ; Middle Aged ; Osteoporosis - epidemiology ; Osteoporosis - metabolism ; Risk Factors ; Spinal Fractures - epidemiology ; Spinal Fractures - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology ; Wnt Signaling Pathway - physiology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2012-10, Vol.97 (10), p.3744-3750</ispartof><rights>Copyright © 2012 by The Endocrine Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4816-87a496cc2ea06b4c0e5d24c67ef9e7d5f30bb74616ec5d8f2636e2e9639c10813</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26450054$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22855334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaudio, Agostino</creatorcontrib><creatorcontrib>Privitera, Filippo</creatorcontrib><creatorcontrib>Battaglia, Katia</creatorcontrib><creatorcontrib>Torrisi, Venerando</creatorcontrib><creatorcontrib>Sidoti, Maria Helga</creatorcontrib><creatorcontrib>Pulvirenti, Ivana</creatorcontrib><creatorcontrib>Canzonieri, Elena</creatorcontrib><creatorcontrib>Tringali, Giovanni</creatorcontrib><creatorcontrib>Fiore, Carmelo Erio</creatorcontrib><title>Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context:
Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling.
Objectives:
The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers.
Design:
This was a cross-sectional study.
Setting and Patients:
The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay.
Results:
Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures.
Conclusions:
These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.</description><subject>Aged</subject><subject>beta Catenin - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Bone Density - physiology</subject><subject>Bone Morphogenetic Proteins - blood</subject><subject>Bone Remodeling - physiology</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Markers</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Osteoporosis - epidemiology</subject><subject>Osteoporosis - metabolism</subject><subject>Risk Factors</subject><subject>Spinal Fractures - epidemiology</subject><subject>Spinal Fractures - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><subject>Wnt Signaling Pathway - physiology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-P1CAYh4nRuOPqzbPhYuLB7gIF2h7X8d8mY0zcMXprKH27ZWRgBLqTvfqR_CB-Jqkz6sVEQkIgz-_lzfsg9JiSM8ooOd_oM0YoK2hD6B20oA0XRUWb6i5aEMJo0VTs8wl6EOOGEMq5KO-jE8ZqIcqSL9C3K20h-JiMwyu4ARvxRYxeG5Wgx3uTRnzpRtOZZLzDfsBpBPzJpfMf34tlZlzOXZlrp6xx11i5Hn-AftI5-8I7wOspOH8DAWdsfbsDzPBLozpIEPE7sNakKT5E9wZlIzw6nqfo4-tX6-XbYvX-zeXyYlVoXlNZ1JXijdSagSKy45qA6BnXsoKhgaoXQ0m6ruKSStCirwcmSwkMGlk2mpKalqfo2aHuLvivE8TUbk3UuQnlwE-xpZLmXUvW_B8ljeBCSFlm9PkB1XmKMcDQ7oLZqnCboXYW1G50OwtqZ0EZf3KsPHVb6P_Av41k4OkRUFErOwTltIl_OckFIWLm-IHbe5sgxC922kNoR1A2jS3Ji8uqLuaf6Xwrfr3kWHmIgeu9DsbBLkCM7cZnU3n6_-76J_0ZuWM</recordid><startdate>201210</startdate><enddate>201210</enddate><creator>Gaudio, Agostino</creator><creator>Privitera, Filippo</creator><creator>Battaglia, Katia</creator><creator>Torrisi, Venerando</creator><creator>Sidoti, Maria Helga</creator><creator>Pulvirenti, Ivana</creator><creator>Canzonieri, Elena</creator><creator>Tringali, Giovanni</creator><creator>Fiore, Carmelo Erio</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope></search><sort><creationdate>201210</creationdate><title>Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus</title><author>Gaudio, Agostino ; Privitera, Filippo ; Battaglia, Katia ; Torrisi, Venerando ; Sidoti, Maria Helga ; Pulvirenti, Ivana ; Canzonieri, Elena ; Tringali, Giovanni ; Fiore, Carmelo Erio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4816-87a496cc2ea06b4c0e5d24c67ef9e7d5f30bb74616ec5d8f2636e2e9639c10813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>beta Catenin - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - metabolism</topic><topic>Bone Density - physiology</topic><topic>Bone Morphogenetic Proteins - blood</topic><topic>Bone Remodeling - physiology</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Osteoporosis - epidemiology</topic><topic>Osteoporosis - metabolism</topic><topic>Risk Factors</topic><topic>Spinal Fractures - epidemiology</topic><topic>Spinal Fractures - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><topic>Wnt Signaling Pathway - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gaudio, Agostino</creatorcontrib><creatorcontrib>Privitera, Filippo</creatorcontrib><creatorcontrib>Battaglia, Katia</creatorcontrib><creatorcontrib>Torrisi, Venerando</creatorcontrib><creatorcontrib>Sidoti, Maria Helga</creatorcontrib><creatorcontrib>Pulvirenti, Ivana</creatorcontrib><creatorcontrib>Canzonieri, Elena</creatorcontrib><creatorcontrib>Tringali, Giovanni</creatorcontrib><creatorcontrib>Fiore, Carmelo Erio</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gaudio, Agostino</au><au>Privitera, Filippo</au><au>Battaglia, Katia</au><au>Torrisi, Venerando</au><au>Sidoti, Maria Helga</au><au>Pulvirenti, Ivana</au><au>Canzonieri, Elena</au><au>Tringali, Giovanni</au><au>Fiore, Carmelo Erio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2012-10</date><risdate>2012</risdate><volume>97</volume><issue>10</issue><spage>3744</spage><epage>3750</epage><pages>3744-3750</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context:
Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with β-catenin, a key component of the Wnt/β-catenin canonical signaling.
Objectives:
The aim of the study was to evaluate the circulating β-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers.
Design:
This was a cross-sectional study.
Setting and Patients:
The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostin and β-catenin were evaluated by an immunoenzymetric assay.
Results:
Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, β-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50–2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20–7.62, respectively; P = 0.0002). β-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures.
Conclusions:
These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>22855334</pmid><doi>10.1210/jc.2012-1901</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Oxford Academic Journals (OUP); Alma/SFX Local Collection; EZB Electronic Journals Library; Journals@Ovid Complete |
subjects | Aged beta Catenin - metabolism Biological and medical sciences Biomarkers - metabolism Bone Density - physiology Bone Morphogenetic Proteins - blood Bone Remodeling - physiology Cross-Sectional Studies Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - metabolism Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Genetic Markers Humans Medical sciences Middle Aged Osteoporosis - epidemiology Osteoporosis - metabolism Risk Factors Spinal Fractures - epidemiology Spinal Fractures - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology Wnt Signaling Pathway - physiology |
title | Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus |
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