Serum Sclerostin and Its Association with Bone Turnover Marker in Metabolic Bone Diseases.
Serum Sclerostin and Its Association with Bone Turnover Marker in Metabolic Bone Diseases.
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硬化蛋白是一种分泌型Wnt/β-catenin信号抑制剂，主要由骨细胞产生，是骨重建的重要调节因子。一些研究评估了代谢性骨病患者血清sclerostin水平，但结果相互矛盾。获得了骨生成障碍（OI）、X连锁低磷血症（XLH）和佩吉特骨病（PDB）患者血清硬化素水平的概况，以确定其与骨转换标志物的相关性。在278例受试者中测定了血清硬化蛋白水平、生化参数和骨转换标志物--含交联C端肽（β-CTX）的1型胶原β-CrossLaps，这些受试者包括71例OI患者、51例XLH患者、17例PDB患者和139例年龄和性别匹配的健康对照。对硬化素与β-CTX浓度进行相关性分析。采用单因素Logistic回归分析OI、XLH和PDB的相关因素。PDB患者男11例，女6例，年龄44.47 ± 14.75岁男17例，女34例，年龄19.29 ± 15.65岁;年龄为19.57 ± 16.45岁（43名男性，28名女性）的硬化素水平高于年龄和性别匹配的健康对照组[中位数（四分位距）：291.60（153.42，357.35）与38.00（27.06，68.52）pmol/L，163.40（125.10，238.20）vs. 31.13（20.37，45.84）pmol/L，和130.50（96.12，160.80）vs. 119.00（98.89，194.80）pmol/L; P < 0.001]。PDB患者血清硬化素水平最高，其次为XLH和OI（P < 0.05）。硬化素与β-CTX在OI和XLH中呈正相关（r分别为0.541和0.661，P < 0.001）。较高的β-CTX和硬化素水平与OI、XLH和PBD的较高风险相关。硬化蛋白可能是OI、XLH和PDB的生物标志物。硬化蛋白抑制剂是否可以用于这些患者需要使用其他队列进行进一步分析。
Sclerostin is a secreted inhibitor of Wnt/β-catenin signaling that is mainly produced by osteocytes and is an important regulator of bone remodeling. Some studies have evaluated serum sclerostin levels in metabolic bone diseases, but the results have been contradictory. The profile of serum sclerostin levels in patients with osteogenesis imperfecta (OI), X-linked hypophosphatemia (XLH), and Paget's disease of bone (PDB) was obtained to determine their association with bone turnover marker. Serum sclerostin levels, biochemical parameters, and the bone turnover marker, β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), were measured in 278 individuals, comprising 71 patients with OI, 51 patients with XLH, 17 patients with PDB, and 139 age- and sex-matched healthy controls. A correlation analysis was performed between sclerostin and β-CTX concentration. The univariate logistic regression analysis was used to analyze factors associated with OI, XLH, and PDB. Patients with PDB (11 male 6 female), aged 44.47 ± 14.75 years; XLH (17 male, 34 female), aged 19.29 ± 15.65 years; and OI (43 male, 28 female), aged 19.57 ± 16.45 years, had higher sclerostin level than age- and sex-matched healthy controls [median(interquartile range): 291.60 (153.42, 357.35) vs. 38.00 (27.06, 68.52) pmol/L, 163.40 (125.10, 238.20) vs. 31.13 (20.37, 45.84) pmol/L, and 130.50 (96.12, 160.80) vs. 119.00 (98.89, 194.80) pmol/L, respectively; P < 0.001]. Patients with PDB had the highest level of serum sclerostin, followed by those with XLH and OI (P < 0.05). Sclerostin was positively correlated with β-CTX in OI and XLH (r = 0.541 and r = 0.661, respectively; P < 0.001). Higher β-CTX and sclerostin levels were associated with a higher risk of OI, XLH, and PBD. Sclerostin may be a biomarker of OI, XLH, and PDB. Whether sclerostin inhibitors can be used in these patients requires further analysis using additional cohorts.
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