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Elevated Circulating Sclerostin Concentrations in Individuals With High Bone Mass, With and Without LRP5 Mutations

Gregson, Celia L. and Poole, Kenneth E. S. and McCloskey, Eugene V. and Duncan, Emma L. and Rittweger, Jörn and Fraser, William D. and Smith, Davey George and Tobias, Jonathan H. (2014) Elevated Circulating Sclerostin Concentrations in Individuals With High Bone Mass, With and Without LRP5 Mutations. Journal of Clinical Endocrinology and Metabolism, 99 (8), pp. 2897-2907. The Endocrine Society. DOI: 10.1210/jc.2013-3958 ISSN 0021-972X

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Abstract

Context: Theroleandimportance of circulating sclerostin is poorly understood. Highbonemass(HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. Objective: Our objective was to determine circulating sclerostin concentrations in HBM. Design and Participants: In this case-control study, 406 HBM index cases were identified by screening dual-energy x-ray absorptiometry (DXA) databases from 4 United Kingdom centers (n = 219 088), excluding significant osteoarthritis/artifact. Controls comprised unaffected relatives and spouses. Main measures: Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated. Results: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases compared with controls: mean (SD) 130.1 (61.7) and 88.0 (39.3) vs 66.4 (32.3) pmol/L (both P < .001, which persisted after adjustment for a priori confounders). In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (ie, L1, total hip, and total body DXA bone mineral density and radial/tibial cortical area, cortical bone mineral density, and trabecular density). Although these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particularly for radial trabecular density (interaction P <.01). Conclusions: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/peripheral quantitative computed tomography parameters, genetic factors predisposing toHBMmaycontribute to increased sclerostin levels. (J Clin Endocrinol Metab 99: 2897–2907, 2014)

Item URL in elib:https://elib.dlr.de/90374/
Document Type:Article
Title:Elevated Circulating Sclerostin Concentrations in Individuals With High Bone Mass, With and Without LRP5 Mutations
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Gregson, Celia L.Musculoskeletal Research Unit (C.L.G., J.H.T.), School of Clinical Sciences, University of Bristol, BristolUNSPECIFIED
Poole, Kenneth E. S.UNSPECIFIEDUNSPECIFIED
McCloskey, Eugene V.UNSPECIFIEDUNSPECIFIED
Duncan, Emma L.UNSPECIFIEDUNSPECIFIED
Rittweger, JörnInstitute of Aerospace Medicine, Deutsches Zentrum für Luft- und Raumfahrt, DLR e.V., Cologne, Germany and Medical Faculty, University of Cologne, Cologne, Germany; joern.rittweger (at) dlr.deUNSPECIFIED
Fraser, William D.UNSPECIFIEDUNSPECIFIED
Smith, Davey GeorgeSchool of Clinical Science, University of BristolUNSPECIFIED
Tobias, Jonathan H.Musculoskeletal Research Unit (C.L.G., J.H.T.), School of Clinical Sciences, University of Bristol, BristolUNSPECIFIED
Date:25 February 2014
Journal or Publication Title:Journal of Clinical Endocrinology and Metabolism
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:99
DOI :10.1210/jc.2013-3958
Page Range:pp. 2897-2907
Publisher:The Endocrine Society
ISSN:0021-972X
Status:Published
Keywords:High Bone Mass, Sclerostin Concentrations, LRP5 Mutations
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Integrative Studien (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Space Physiology
Deposited By: Becker, Christine
Deposited On:26 Aug 2014 12:17
Last Modified:06 Sep 2019 15:22

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