11β-hydroxysteroid dehydrogenase type 1 activity predicts the effects of glucocorticoids on bone
11β-hydroxysteroid dehydrogenase type 1 activity predicts the effects of glucocorticoids on bone
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DOI：
10.1210/jc.2003-022025
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发表时间：
2003-08-01
影响因子：
5.8
通讯作者：
Stewart, PM
中科院分区：
文献类型：
--
作者：
Cooper, MS;Blumsohn, A;Stewart, PM
个体对糖皮质激素所致骨质疏松症的易感性在临床上很难预测。我们最近表征了11β -羟基类固醇脱氢酶1型（11β - hsd1）在人成骨细胞中的表达。这种酶从无活性的可的松（或强的松）产生活性的皮质醇（或强的松），并在体外调节糖皮质激素的作用。因此，我们假设成骨细胞11 β - hsd1介导糖皮质激素诱导的骨质疏松症的易感性。20名健康男性服用5毫克强的松龙，每天两次，连续7天，并检查骨转换标志物的变化与尿中皮质类固醇代谢指标之间的关系。所有受试者骨形成标志物骨钙素和I型胶原n端前肽均下降（P < 0.001），但骨吸收标志物不变。11 β - hsd1基线活性与形成标志物的下降程度相关，高活性预测最大的下降[骨钙素d 4和7，r = -0.58和-0.56 (P < 0.01)]；I型胶原d 4 n端前肽，r = - 0.51 （P < 0.05）。与糖皮质激素失活或总糖皮质激素代谢物的产生没有相关性。尿液中11 β - hsd1活性的测量预测了骨形成标志物对糖皮质激素的反应，这似乎反映了成骨细胞中活性糖皮质激素的增加。11 β - hsd1活性的测量可以预测个体对糖皮质激素诱导的骨质疏松症的易感性，这些数据应该促进保骨糖皮质激素的开发。
Individual susceptibility to glucocorticoid-induced osteoporosis is difficult to predict clinically. We recently characterized expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in human osteoblasts. This enzyme generates active cortisol ( or prednisolone) from inactive cortisone ( or prednisone) and regulates glucocorticoid action in vitro. We, thus, hypothesized that osteoblastic 11beta-HSD1 mediates susceptibility to glucocorticoid-induced osteoporosis. Twenty healthy males ingested 5 mg prednisolone twice daily for 7 d, and relationships between changes in bone turnover markers and urinary measures of corticosteroid metabolism were examined. The bone formation markers osteocalcin and N-terminal propeptide of type I collagen decreased in all subjects ( P < 0.001), but resorption markers were unchanged. The extent of fall in formation markers correlated with baseline 11 beta-HSD1 activity with high activity predicting the greatest fall [ for osteocalcin d 4 and 7, r = -0.58 and -0.56 ( P < 0.01); for N-terminal propeptide of type I collagen d 4, r = - 0.51 ( P < 0.05)]. There was no correlation with measures of glucocorticoid inactivation or total corticosteroid metabolite production. Urinary measures of 11 beta-HSD1 activity predict the response of bone formation markers to glucocorticoids, and this appears to reflect increased generation of active glucocorticoids within osteoblasts. Measures of 11 beta-HSD1 activity may predict individual susceptibility to glucocorticoid-induced osteoporosis, and these data should facilitate the development of bone-sparing glucocorticoids.