The Study Of Animal Model Of Glucocorticoid Induced Osteoporosis

Objective:On the basement of rats which subtotal adrenalectomy had been carried on, cure the animal by glucocorticoid, animal model of Glucocorticoid Induced Osteoporosis (GIO) stimulated the clinic has been established. Methods: Select40Sprague-Dawley rats of8-12weeks, the mean weight was244.87±18.86g. The rats were divided into5groups by random, that were group A (natural control group), group B(therapy control group), group C(small dose therapy group), D(middle dose therapy group) and group E(large dose therapy group). All of the rats were given Vitamin D310,000IU/100g·BW by intramuscular injection before operation. Negative operation was performed on the rats of group A in which the adrenal glands had been destroyed; In B, C, D, and E group, subtotal adrenalectomy had been performed. After operated, all the rats were fed in normal situation, the room temperature was about24±2℃,. In the following4weeks, A and B groups were given balms, C, D and E group were treated with different doses of prednisone respectively:C group:0.1mg/100g-BW-day, D group:0.5mg/100g-BW-day and E group:lmg/100g·BW-day. The rats were weighted and the24hours urine was collected for measuring the weight each2weeks. When it was0week,2weeks,4weeks,6weeks after operation, the blood was taken and the level of serum Ca, P, ACTH, cortical hormones and1,25(OH)2D3were measured every two weeks; all rats were checked the mineral density of lumbar and femur bone at the beginning and the final. The femurs were reserved for the measure of the bone’s biomechanical parameter. Results:After the subtotal adrenalectomy, the indexes of blood examination shows:①2weeks after the operation, compare with group A, there were a declined cortisone and elevated ACTH in serum in group B(P<0.05), C, D and E while the serum Ca, P and1,25(OH)2D3were significantly declined (P<0.05) With the replacement therapy of glucocorticoid, the level of ACTH and cortisone has came back, but still lower than A group;②4weeks after the operation, the therapy with prednisone had begun, compare with group A, the serum Ca, P and1,25(OH) 2D3of operative group had not changed; Compare with group B, the level of serum1,25(OH)2D3of group C, D and E were significantly elevated (P<0.05).③6weeks after the operation, compare with group A, the level of serum P and1,25(OH)2D3of therapy groups were significantly declined (P<0.05), serum Ca had not changed; Compare with group B, the level of serum Ca of C group with small dose was significantly elevated (P<0.05);1,25(OH)2D3of group C, D and E was significantly elevated (P<0.05). The level of serum P had not changed. The result of bone density suggests:Compare with group A, the bone density of operative groups were significantly declined (P<0.05); compare with group B, suggesting that C group with prednisone of small dose was significantly elevated, the degree of recovery has obvious related with the dose of GC. The biomechanical property parameters of femur shows:compare with group A, in group C, D and E, Gpa, maximal bending stress, and bending rigidity parameter were significantly declined (P<0.05); bending tenacity parameter were significantly elevated (P<0.05). The degree of recovery has no obvious related with the dose of GC. Conclusion:1. Subtotal adrenalectomy caused the happened of hypadrenia of rats, on the basement of it, use glucocorticoid on animal, the change of bone metabolism of glucocorticoid on induced osteoporosis had come into being;2.According to the change of the level of serum biochemistry indexes, the mineral density of lumbar and femur bone and the bone’s biomechanical parameter, it established that the lose of bone was serious in the group with middle and large doses, it shows the building of GIO animal model by large dose of glucocorticoid has a high rate of succeed;3. Glucocorticoid has two-way accommodation effects on osteoporosis:small dose does benefit to the recover of bone damage, large dose does harm to the recover of bone damage.2. On the basement of subtotal adrenalectomy, give glucocorticoid to rats, the successful establishment of animal model of GIO was consistent with development of GIO in clinical field.