The Clinical And Experimental Study Of Glucocorticoid Effects On Vitamin D And Bone Metabolism

Objective: To investigate the effects of various dose of glucocorticoids on bone metabolism in subtotal adrenalectomized rats. Methods: 40 8¹2 weeks Sprague-Dawley rats,weights ranged from 205²90g, the mean body weight was 244.17 ± 18.86g, were divided in to 5 groups randomly, they were group A,B,C,D,and E, grop A was control group, the others were model group. All of the rats were given Vitamin D₃ 10000 IU/100g BW by intramuscular injection, one side of the adrenal gland was completely removed from the model groups and the other was partially ectomized. Before and after the operation, the blood was taken and the 24-hours urine was collected for measuring the biological indices; two weeks later, the rats in the group C,D and E were treated with various doses of prednisone respectively, the doses were 0.lmg/100g BW?d, 0.5mg/100g BW ?d and lmg/lOOg BW ? d. The rats were weighted each week,the room tempreture was about 24+2°C, the samples were taken every other week. Results: After the subtotal adrenalectomy, in comparison with group A, there were a declined cortisone and elevated ACTH in serum from group B,C,D and E while the serum Ca,P and 1,25(OH)₂D₃ were significantly declined. When the replacement therapy was initiated with various doses prednisone, in comparison with group B, thesubtotal adrenalectomized rats; Sprague-Dawley rats ; 25-hydroxyvitamin D₃ ; 1,25-dihydroxyvitamin D₃; parathyroid hormone; Adrenocorticotropic Hormone; cortisone; prednisoneThe part 2: Efects of prednisone on bone histomorphometry in subtotal adrenalectomized rats[ Abstract ] Objective: to investigate the effects of various dose of glucocorticoids on bone metabolism in subtotal adrenalectomized rats by bone histomorphometry, bone mineral density(BMD) and bone biomechanical properties. Methods: Forty male Sprague-Dawley rats, aged at 2³ months, were divided in to following groups randomly:Group A,B,C,D, and E. Group A was control group, the others were model groups whose one side of the adrenalglands ectomized and the other one partially ectomized. All of the rats were given Vitamin D3 10000 IU/100 g ? BW by intramuscular injection. Two weeks later, the rats in the group C(0.1mg/100g BW ? d), D(0.5mg/100g BW ? d) and E(lmg/100g BW ? d) were treated with various doses of prednisone respectively, All of 5 groups of rats were fed for 8 weeks with regular solid food and tap water. On the 14th and 6th day prior to sacrifice, 100mg/100g-BW tetracycline was given by gavage to the rats in order to label the bone for dynamic study. The bilateral tibia and femur were dissected out, the proximal portion of tibia on the left was reserved of each rat for the preparation of undecalcified bone specimen which was used for bone histomorphometric study including trabecular volume, trabecular thickness, and the dynamic indices.Biomechanical property parameters of femur were measured with three point bending tests. The BMD of total femur, distal femur metaphysis were measured by dual energy X-ray absorptiometry. Results: the static data showed that TBV and trabecular thickness of Group B were significantly reduced in comparision with the control group. TBV/TTV, TBV/SBV, and MDPD were significantly increased in Group C than that in group B, associated with obvious decrease in MTPS. But in large dose of prednisone replacement groups, comparing with control group, TBV/TTV, TBV/SBV, and MDPD were significantly decreased and MTPS was increased.The dynamic analysis indicated that Sfract(d), Sfract(s) and Sfract (s/2+d) were significantly decreased ,while TOS was obvious increased in group B comparing with group A, the bone loss seemed to be associated with the decrease in bone formation and the mineralization . in the small dose of prednisone group, the Sfract(d), Sfract(s) and Sfract (s/2+d) were slightly increased as well as decreased TOS in comparison with group B. in group D and E, however, Sfract(d), Sfract(s) and Sfract (s/2+d) were significantly decreased, associatedwith TOS increased, suggesting that prednisone at large dose could inhibit bone formation and bone mineralization. Conclusion: Prednisone could have biphasic effects on the bone structure. Also the bone formation and bone mineralization were inhibited when absolute deficiency in cortisone occured, prednisone replacement at large dose might depress the bone formation and bone mineralization, leading to bone loss. The data suggest that prednisone at small dose may benefit the bone metabolism and Biomechanics in subtotal adrenalectomized rats.density; Bone histomorphometry; Biomechanics; Bone formation; Bone mineralization.The part 3: The Study of 1,25-dihydroxyvitamin D3 in T2 DM patients with hyponatremia[Abstract] Objective: To investigate the effects of vitamin D3 deficiency on the development and progression of Type 2 diabetes, the pathogenesis of type 2 diabetes with hyponatremia, and the effect of cortisone on metabolism of vitamin D3. Methods: 50 healthy subjects and 80 type 2 diabetic patients were recruited into our study. The concentration of 25(OH)D3 and 1,25(OH)2D3 were measured by radioimmunoassay respectively at the baseline and after the treatment with prednisone. Results: in contrast to control group, the concentration of25(OH)D3 and 1,25(OH)2D3 were significantly decreased in type 2 diabetes group(P < 0.05). The 25(OH)D3 and 1,25(OH)2D3 from the male patients were higher than that in the female, but there was no significant differences between two groups(P > 0.05). After injection of Vitamin D3, 25(OH)D3 was increased in type 2 diabetes groups while 1,25(OH)2D3 were slightly increased with no difference in comparison with that in baseline. 25(OH)D3 and 1,25(OH)2D3 were no differences between diabetes with and without retinopathy. The prevalence of hyponatremia, hypocalcemia and hypoalbuminemia in type 2 diabetes were 18.32%, 15.71% and 19.89%, respectively. There were close correlation among hyponatremia, hypocalcemia and hypoalbuminemia in type 2 diabetes. In comparison with normal natrium group, the 25(OH)D3 and 1,25(OH)2D3 in hyponatremia group were not decreased significantly. After the injection of Vitamin D3, however, the 1,25(OH)2D3 was significantly increased in normal natrium group while there was no significant increase in the hyponatrimia group. When prednisone at small dose was initiated, the 1,25(OH)2D3 levels was significantly increased while the 25(OH)D3 levels remained the same as before. Conclusion: Deficiency in vitamin D3 is closely associated with the development and progression of type 2 diabetes. It is possible that the deficiency in vitamin D3 could damage the release of insulin in type 2 diabetes. There is a relative insufficiency to glucocorticoids in type 2 diabetes clinical characterized by hyponatremia which could be , prednisone could up regulate the activation of 1 -a hydroxylase in the kidney of type 2 diabetes with hyponatremia and raise the calcium in serum to balance the calcium and phosphate metabolism.