Departments of Pathology (T.C.R.), Public Health Sciences (J.D., L.E.W., C.D.L.), Radiology (T.C.R., J.J.C., R.C.H.), and Internal Medicine/Nephrology (B.I.F.) and Center for Genomics and Personalized Medicine Research (D.W.B., N.D.P., J.X., S.C.S.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157; and Department of Pediatric Nephrology (K.A.H., D.J.D.), Washington University School of Medicine, St Louis, Missouri 63110.
J Clin Endocrinol Metab. 2014 Jan;99(1):315-21. doi: 10.1210/jc.2013-3168. Epub 2013 Dec 20.
Bone mineral density (BMD) and calcified atherosclerotic plaque (CP) demonstrate inverse relationships. Sclerostin, an endogenous regulator of the Wnt pathway and bone formation, has been associated with impaired osteoblast activation and may play a role in vascular calcification.
Our objective was to assess the relationships between sclerostin, BMD, and CP.
Generalized linear models were fitted to test for associations between sclerostin, volumetric BMD (vBMD), and CP.
A targeted population of 450 unrelated African Americans (AAs) with type 2 diabetes (T2D) was 56% female with mean/SD/median age of 55.4/9.5/55.0 years and a diabetes duration of 10.3/8.2/8.0 years.
Plasma sclerostin, computed tomography-derived thoracic and lumbar vertebrae trabecular vBMD, coronary artery, carotid artery, and aortoiliac CP were measured.
Plasma sclerostin was 1119/401/1040 pg/mL, thoracic vBMD was 206.3/52.4/204.8 mg/cm3, lumbar vBMD was 180.7/47.0/179.0 mg/cm3, coronary artery CP score was 284/648/13, carotid artery CP score was 46/132/0, and aortoiliac CP score was 1613/2910/282. Sclerostin levels were higher in men than women (P<.0001). Before and after adjusting for age, sex, body mass index, blood pressure, smoking, hemoglobin A1c, and low-density lipoprotein-cholesterol, plasma sclerostin levels were positively associated with thoracic and lumbar vertebrae vBMD (P<.0001). Sex-stratified analyses verified significant relationships in both men and women (both P<.001). Sclerostin was not associated with CP except for an inverse relationship with carotid CP in men (fully adjusted model, P=.03).
In this cross-sectional study of AA men and women with T2D, circulating sclerostin was positively associated with vBMD in the spine in both sexes and inversely associated with carotid artery CP in men. Sclerostin may play a role in skeletal mineral metabolism in AA but fails to explain inverse relationships between BMD and CP.
骨密度（BMD）和钙化粥样斑块（CP）呈负相关。骨硬化蛋白是 Wnt 通路和骨形成的内源性调节剂，与成骨细胞激活受损有关，可能在血管钙化中发挥作用。
本研究旨在评估骨硬化蛋白与 BMD 和 CP 的关系。
广义线性模型拟合检验骨硬化蛋白、容积 BMD（vBMD）和 CP 之间的相关性。
本研究纳入了 450 名非裔美国人（AA）的目标人群，他们患有 2 型糖尿病（T2D），其中 56%为女性，平均年龄/标准差/中位数为 55.4/9.5/55.0 岁，糖尿病病程为 10.3/8.2/8.0 年。
检测血浆骨硬化蛋白、计算机断层扫描（CT）检测的胸腰椎小梁 vBMD、冠状动脉、颈动脉和腹主动脉髂动脉 CP。
血浆骨硬化蛋白为 1119/401/1040 pg/ml，胸腰椎 vBMD 为 206.3/52.4/204.8 mg/cm3，腰椎 vBMD 为 180.7/47.0/179.0 mg/cm3，冠状动脉 CP 评分 284/648/13，颈动脉 CP 评分 46/132/0，腹主动脉髂动脉 CP 评分 1613/2910/282。男性的骨硬化蛋白水平高于女性（P<.0001）。在校正年龄、性别、体重指数、血压、吸烟、糖化血红蛋白和低密度脂蛋白胆固醇后，血浆骨硬化蛋白水平与胸腰椎 vBMD 呈正相关（P<.0001）。性别分层分析验证了男性和女性均存在显著相关性（均 P<.001）。除了与男性颈动脉 CP 呈负相关（完全校正模型，P=.03）外，骨硬化蛋白与 CP 无相关性。
在这项非裔美国人 2 型糖尿病男性和女性的横断面研究中，循环骨硬化蛋白与男女脊柱 vBMD 呈正相关，与男性颈动脉 CP 呈负相关。骨硬化蛋白可能在非裔美国人的骨骼矿物质代谢中发挥作用，但不能解释 BMD 和 CP 之间的负相关。
