Effect of 11β-HSD1 dehydrogenase activity on bone histomorphometry of glucocorticoid-induced osteoporotic male Sprague-Dawley rats

<p><b>INTRODUCTION</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Adequacy of pain relief in closed manipulative reduction of fracture and dislocation

Adequate pain relief is a requisite for a successful closed manipulative reduction (CMR) of fractures and dislocations. This prospective study was undertaken to assess the mode and adequacy of pain relief given to patients undergoing such procedures at Seremban Hospital from the 1st April to the 31st May 2001. All patients with fractures and dislocations scheduled to undergo CMR were included in this study. The type of sedative agents and analgesia administered were recorded. Demographic data and the type of fracture or dislocation of the selected patients were documented. A visual analogue scale (VAS) for pain perception was given to both to the patients and the medical personnel who performed the procedure. All data were collected manually before entered into computerized database for analysis. Of 72 patients included in this study, 47% were Malay, 26% Indian, 21% Chinese and 6% others. There was male predominance and the patients' age ranged between 9 to 79 years (average 27.4 years). Upper limb injuries (79%) were mainly fractures of the radius and ulna (29%) and isolated fracture radius (21%). For the lower limb injuries (21%), combined tibia and fibula fractures constituted 10% of the total cases followed by isolated tibia fractures (10%) and hip dislocation (1%). The most common pain relieving agents given during the CMR were intravenous pethidine alone (43%) followed by combination of intravenous pethidine and valium (36%), intramuscular pethidine (17%) and intramuscular tramal (4%). The Visual Analogue Score (VAS) for pain perception revealed that 61% of the patients had moderate pain while 21% had severe pain during the course of the procedures. Suboptimal pain relief administered during CMR should prompt positive actions to ensure that the patient is not subjected to undue pain just for the sake of an acceptable fracture reduction.