Elvy Suhana MR, Farihah HS, Faizah O, Nazrun AS, Norazlina M, Norliza M, Ima-Nirwana S
Correspondence: Prof Dr Ima-Nirwana Soelaiman, imasoel@medic.ukm.my
ABSTRACT
Introduction Glucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-betahydroxysteroid dehydrogenase type 1 (11ßHSD1) enzyme, which plays an important role in regulating corticosteroids. 11ß-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11ß-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoidinduced osteoporotic bone in rats.
Methods 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 11ß-HSD1 were measured, and bone histomorphometry analysis was performed.
Results Dexamethasone treatment caused an increase in plasma corticosterone level, together with a significant reduction in 11ß-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.
Conclusion Long-term glucocorticoid treatment reduces the 11ß-HSD1 dehydrogenase activity in the bone, which can otherwise lead to bone loss due to the increased level of active glucocorticoids.
Keywords: 11-beta-hydroxysteroid dehydrogenase type 1, bone, dexamethasone, glucocorticoids, osteoporosis
Singapore Med J 2011; 52(11): 786-793
