Gregson Celia L, Poole Kenneth E S, McCloskey Eugene V, Duncan Emma L, Rittweger Jörn, Fraser William D, Smith George Davey, Tobias Jonathan H
Musculoskeletal Research Unit (C.L.G., J.H.T.), School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, United Kingdom; Medical Research Council (MRC) Lifecourse Epidemiology Unit (C.L.G.), University of Southampton, Southampton, SO16 6YD United Kingdom; Department of Medicine (K.E.S.P.), University of Cambridge, Cambridge, CB2 0SP United Kingdom; Metabolic Bone Centre (E.V.M.), Sheffield University, Sheffield, S3 7HF United Kingdom; Human Genetics Group (E.L.D.), University of Queensland Diamantina Institute, Brisbane, Australia; Department of Endocrinology (E.L.D), Royal Brisbane and Women's Hospital, Brisbane, Australia; Institute of Aerospace Medicine (J.R.), German Aerospace Center (Deutschen Zentrums fuür Luft- und Raumfahrt), Cologne, Germany; Institute for Biomedical Research into Human Movement and Health Research Institute (J.R.), Manchester Metropolitan University, Manchester, M1 5GD United Kingdom; Department of Medicine (W.D.F.), Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ United Kingdom; and MRC Integrative Epidemiology Unit (G.D.S.), School of Social and Community Based Medicine, University of Bristol, Bristol, BS8 2BN United Kingdom.
J Clin Endocrinol Metab. 2014 Aug;99(8):2897-907. doi: 10.1210/jc.2013-3958. Epub 2014 Feb 25.
The role and importance of circulating sclerostin is poorly understood. High bone mass (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.
Our objective was to determine circulating sclerostin concentrations in HBM.
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.
Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated.
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).
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 to HBM may contribute to increased sclerostin levels.
循环骨硬化蛋白的作用和重要性尚不清楚。据报道，由激活LRP5突变引起的高骨量（HBM）与血浆骨硬化蛋白浓度升高有关；对于其他原因导致的HBM是否也是如此尚不清楚。
我们的目的是测定HBM患者循环骨硬化蛋白的浓度。
在这项病例对照研究中，通过筛查来自英国4个中心（n = 219 088）的双能X线吸收法（DXA）数据库，排除严重骨关节炎/伪影，确定了406例HBM指数病例。对照组包括未受影响的亲属和配偶。
评估血浆骨硬化蛋白；腰椎L1、全髋和全身DXA；以及桡骨和胫骨外周定量计算机断层扫描（仅亚组）。
与对照组相比，LRP5 HBM和非LRP5 HBM病例的骨硬化蛋白浓度均显著升高：平均值（标准差）分别为130.1（61.7）和88.0（39.3），而对照组为66.4（32.3）pmol/L（两者P <.001，在对先验混杂因素进行调整后仍然成立）。在病例和对照的联合调整分析中，骨硬化蛋白浓度与HBM病例中发现升高的所有骨参数呈正相关（即L1、全髋和全身DXA骨密度以及桡骨/胫骨皮质面积、皮质骨矿物质密度和小梁密度）。虽然这些关系在HBM病例和对照中大致相同，但有一些证据表明，骨硬化蛋白与小梁表型之间的关联在HBM病例中更强，特别是对于桡骨小梁密度（交互作用P <.01）。
与对照组相比，LRP5和非LRP5 HBM患者的循环血浆骨硬化蛋白浓度均升高。除了骨硬化蛋白与DXA/外周定量计算机断层扫描参数之间的一般正相关关系外，导致HBM的遗传因素可能导致骨硬化蛋白水平升高。
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