The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy.
The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy.
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DOI：
10.1186/s12902-020-00633-1
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发表时间：
2020-10-10
影响因子：
2.7
通讯作者：
Sherlock M
中科院分区：
文献类型：
--
作者：
Dineen R;Behan LA;Kelleher G;Hannon MJ;Brady JJ;Rogers B;Keevil BG;Tormey W;Smith D;Thompson CJ;McKenna MJ;Arlt W;Stewart PM;Agha A;Sherlock M
糖皮质激素治疗是医源性骨质疏松症最常见的原因。在肾上腺功能不全患者中，糖皮质激素作为替代疗法用于骨重塑的效果尚不清楚。11β-羟基类固醇脱氢酶1型（11β- hsd1）和其他导致糖皮质激素代谢改变的酶在细胞内将非活性可的松转化为活性可的松的增强，可能对该患者组的骨骼健康产生有害影响。研究设计：一项开放交叉前瞻性研究，将10名严重ACTH缺乏的垂体功能低下男性随机分为三种常用的氢化可的松剂量方案。测量：在每个治疗方案6周后，患者进行24小时血清皮质醇/可的松取样，测量骨转换标志物，并收集24小时尿液，通过气相色谱-质谱（GC-MS）测量尿类固醇代谢物。采用液相色谱-质谱法（LC-MS）分析血清可的松和皮质醇。血清可的松的剂量相关和昼夜变化与皮质醇相似，表明摄入的氢化可的松转化为可的松。A剂量组血清可的松曲线下中位面积（AUC） （20 mg/10 mg） [670.5 (IQR 621-809.2)]显著高于C剂量组（10 mg/5 mg） [562.8 (IQR 520.1-619.6), p = 0.01]。血清可的松与骨形成标志物OC [1-49] （r = - 0.42, p = 0.03）、PINP （r = - 0.49, p = 0.01）呈负相关。夜间血清可的松AUC与骨形成标志物OC呈负相关[1-49](r = - 0.41, p = 0.03)，而日间血清可的松或皮质醇与骨转换标志物无显著相关性。尿总皮质醇代谢物与骨形成标志物PINP （r = - 0.39, p = 0.04）和OC [1-49] （r = - 0.35, p = 0.06）呈负相关。在接受替代剂量氢化可的松治疗的患者中，血清皮质醇、可的松和尿皮质类固醇总代谢物与骨转换标志物呈负相关，夜间糖皮质激素暴露对骨转换的潜在影响更大。爱尔兰药品委员会临床试验编号：CT900/459/1和欧洲药品草案编号：2007-005018-37。注册日期：07-09-2007。
Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = − 0.39, p = 0.04), and OC [1–49] (r = − 0.35, p = 0.06). Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. Irish Medicines Board Clinical Trial Number – CT900/459/1 and EudraCT Number – 2007-005018-37. Registration date: 07-09-2007.
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DOI：
10.1210/jc.2011-1565
发表时间：
2011-12
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Arlt W;Biehl M;Taylor AE;Hahner S;Libé R;Hughes BA;Schneider P;Smith DJ;Stiekema H;Krone N;Porfiri E;Opocher G;Bertherat J;Mantero F;Allolio B;Terzolo M;Nightingale P;Shackleton CH;Bertagna X;Fassnacht M;Stewart PM
通讯作者：
Stewart PM
影响因子：
5.8
作者：
Cooper, MS;Blumsohn, A;Stewart, PM
通讯作者：
Stewart, PM
影响因子：
4
作者：
Braatvedt, GD;Joyce, M;Reid, IR
通讯作者：
Reid, IR
影响因子：
2.2
作者：
FEW, JD;CASHMORE, GC
通讯作者：
CASHMORE, GC
影响因子：
12.8
作者：
Hardy RS;Fenton C;Croft AP;Naylor AJ;Begum R;Desanti G;Buckley CD;Lavery G;Cooper MS;Raza K
通讯作者：
Raza K