Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
J Clin Endocrinol Metab. 2012 Oct;97(10):E1953-7. doi: 10.1210/jc.2012-2218. Epub 2012 Jul 27.
Increased bone fragility is a frequent complication of hypercortisolism due predominantly to suppression of bone formation. Sclerostin is an osteocyte-produced negative regulator of bone formation, which is up-regulated by glucocorticoids in mice.
Our objective was to assess the effect of endogenous hypercortisolism on circulating sclerostin and bone turnover in humans.
We measured sclerostin, β-C-terminal telopeptide, amino-terminal propeptide of type 1 procollagen, and fibroblast growth factor 23 in blood samples of 21 patients with endogenous hypercortisolism and 21 age- and gender-matched controls. In 12 patients, measurements were repeated at various time intervals after successful surgical treatment (transsphenoidal surgery or adrenalectomy).
Plasma sclerostin levels were significantly decreased in patients compared with controls (112±49 vs. 207±48 pg/ml, P<0.001). In the 12 patients who were evaluated after surgical treatment, sclerostin levels increased from 121.4±46.5 to 175.8±78.5 pg/ml (P=0.003). These changes in plasma sclerostin levels were accompanied by significant increases in levels of fibroblast growth factor 23 (from 44.2±12.2 to 84.0±58.8 pg/ml, P=0.017) and of the bone turnover markers amino-terminal propeptide of type 1 procollagen (from 31.7±18.2 to 94.2±92.2 ng/ml, P=0.037) and β-C-terminal telopeptide (from 134.2±44 to 409.2±285 pg/ml, P=0.005).
Contrary to the findings in mice, circulating sclerostin is decreased in patients with chronic endogenous hypercortisolism and increases after treatment. These findings suggest that in humans, chronic exposure to glucocorticoids affects the number or function of osteocytes rather than the production of sclerostin.
由于骨形成的抑制，皮质醇增多症患者常出现骨脆性增加，这是一种常见的并发症。骨硬化蛋白是一种成骨细胞产生的骨形成负调节剂，在小鼠中受糖皮质激素上调。
我们旨在评估内源性皮质醇过多症对人体循环骨硬化蛋白和骨转换的影响。
我们测量了 21 例内源性皮质醇过多症患者和 21 名年龄和性别匹配的对照者的血液样本中的骨硬化蛋白、β- C 端肽、I 型前胶原氨基端前肽和成纤维细胞生长因子 23。在 12 例患者中，在成功的手术治疗（经蝶窦手术或肾上腺切除术）后的不同时间间隔重复测量。
与对照组相比，患者的血浆骨硬化蛋白水平显著降低（112±49 与 207±48 pg/ml，P<0.001）。在 12 例接受手术治疗后评估的患者中，骨硬化蛋白水平从 121.4±46.5 增加到 175.8±78.5 pg/ml（P=0.003）。血浆骨硬化蛋白水平的这些变化伴随着成纤维细胞生长因子 23（从 44.2±12.2 增加到 84.0±58.8 pg/ml，P=0.017）和骨转换标志物 I 型前胶原氨基端前肽（从 31.7±18.2 增加到 94.2±92.2 ng/ml，P=0.037）和β- C 端肽（从 134.2±44 增加到 409.2±285 pg/ml，P=0.005）水平的显著增加。
与小鼠的研究结果相反，慢性内源性皮质醇过多症患者的循环骨硬化蛋白减少，治疗后增加。这些发现表明，在人类中，慢性糖皮质激素暴露会影响成骨细胞的数量或功能，而不是骨硬化蛋白的产生。
