Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
Singapore Med J. 2011 Nov;52(11):786-93.
Glucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, which plays an important role in regulating corticosteroids. 11β-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11β-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoid-induced osteoporotic bone in rats.
A total of 30 male Sprague-Dawley rats (aged three months, weighing 200-250 g) were divided into three groups of ten each. Group 1 rats were the baseline control, which were sacrificed untreated at the beginning of the study. Group 2 rats underwent sham operation and were administered with vehicle olive oil intramuscularly at 0.05 ml/kg. Group 3 rats were adrenalectomised and administered with an intramuscular injection of dexamethasone 120 μg/kg body weight/day. The treatment was started two weeks after the operation, for a duration of two months. Plasma osteocalcin, plasma pyrodinoline, plasma corticosterone and 11β-HSD1 were measured, and bone histomorphometry analysis was performed.
Dexamethasone treatment caused an increase in plasma corticosterone level, together with a significant reduction in 11β-HSD1 dehydrogenase activity of the bone, along with a higher plasma level of the bone resorption marker, pyridinoline. Dexamethasone treatment also caused a reduction in trabecular volume, number and thickness, and an increase in trabecular separation.
Long-term glucocorticoid treatment reduces the 11β-HSD1 dehydrogenase activity in the bone, which can otherwise lead to bone loss due to the increased level of active glucocorticoids.
糖皮质激素通过减少骨形成和增加骨吸收活性导致骨质疏松。糖皮质激素在骨骼中的作用取决于 11-β-羟类固醇脱氢酶 1 型（11β-HSD1）酶的活性，该酶在调节皮质类固醇方面发挥着重要作用。11β-HSD1 由人和大鼠成骨细胞表达。我们旨在研究大鼠糖皮质激素诱导骨质疏松骨中 11β-HSD1 脱氢酶活性与骨组织形态计量学变化之间的关系。
共 30 只雄性 Sprague-Dawley 大鼠（3 月龄，体重 200-250 g）分为 3 组，每组 10 只。第 1 组为基线对照组，在研究开始时未经处理即被处死。第 2 组大鼠接受假手术，并给予 0.05ml/kg 肌肉注射橄榄油。第 3 组大鼠接受肾上腺切除术，并给予肌肉注射地塞米松 120μg/kg 体重/天。术后两周开始治疗，持续两个月。测量血浆骨钙素、血浆吡啶啉、血浆皮质酮和 11β-HSD1，并进行骨组织形态计量学分析。
地塞米松治疗导致血浆皮质酮水平升高，同时骨 11β-HSD1 脱氢酶活性显著降低，骨吸收标志物吡啶啉的血浆水平升高。地塞米松治疗还导致小梁体积、数量和厚度减少，小梁分离增加。
长期糖皮质激素治疗降低了骨中的 11β-HSD1 脱氢酶活性，否则会因活性糖皮质激素水平升高而导致骨丢失。
