糖質コルチコイド誘発骨粗鬆症の発症機序並びに治療に関する研究
スポンサーリンク
概要
- 論文の詳細を見る
Histological studies of bone in hypercortisolism have demonstrated both decreased bone formation and increased bone resorption. It has previously been shown that secondary hyperparathyroidism may contribute to increased bone resorption in patients under glucocorticoid therapy and that increased urinary calcium excretion plays an important role in the development of secondary hyperparathyroidism. On the other hand, it has also been reported that intestinal calcium absorption decreases during glucocorticoid therapy. However, the exact mechanism and the role of altered vitamin D metabolism for the impaired calcium absorption remains to be established.<BR>In this study, vitamin D metabolism and intestinal calcium absorption were investigated in 18 patients with collagen diseases under glucocorticoid therapy (steroid group) and in 22 control subjects (non-steroid group), which included patients with collagen diseases who were not receiving glucocorticoid, and 14 normal volunteers. Furthermore, we examined the effects of thiazide and 1 alpha-hydroxy-vitamin D<SUB>3</SUB> (1 alpha-OH-D<SUB>3</SUB>) on parathyroid function and calcium metabolism in patients who showed obvious secondary hyperparathyroidism.<BR>Plasma 25-hydroxyvitamin D (250HD) and la, 25-dihydroxy vitamin D [1, 25 (OH) <SUB>2</SUB> D] were determined according to the method of Mallon, et al. An oral calcium tolerance test was performed according to the method introduced by Broadus et al. Serum and urinary calcium response to 1g of oral calcium load and changes in nephrogenous cyclic AMP (cAMP) and serum immunoreactive parathyroid hormone (iPTH) were determined as the indices of intestinal calcium absorption.<BR>The mean of 250HD in patients with collagen diseases who were not receiving glucocorticoid [11.6 ± 4.1 (± SD) ng/ml] and that in patients under glucocorticoid therapy (9.2 ± 3.2) was significantly lower than that in normal subjects (18.5 ± 4.4) (p<0.01, p<0.001, respectively). The decreased plasma 250HD in patients with collagen diseases regardless of glucocorticoid therapy was not caused by the administration of glucocorticoid, but by other factors, such as insufficient exposure to sunlight or nutritional factors. In contrast, the mean of plasma 1, 25 (OH) <SUB>2</SUB> D in patients under glucocorticoid therapy (27.3 ± 7.9 pg/ml) was significantly decreased, compared with that in patients with collagen diseases who were not receiving glucocorticoid (35.6 ± 9.2) (p<0.02) and that in normal subjects (41.2 ± 5.0) (p<0.001). After the administration of glucocorticoid, plasma 1, 25 (OH) <SUB>2</SUB> D decreased in all patients except one who had been prescribed glucocorticoid for only 3 weeks. The mean of calciuric responses in the steroid group was essentially identical with that in the nonsteroid group. In contrast, the mean of calcemic responses in the steroid group (0.29 ± 0.21 mg/di) was significantly lower than that in the non-steroid group (0.51 ± 0.24) (p<0.01). These results suggested that intestinal calcium absorption decreased in the steroid group. Plasma 1, 25 (OH) <SUB>2</SUB> D correlated positively with calcemic response in all subjects (r=0.599, p<0.001). However, there was no significant correlation between plasma 1, 25 (OH) <SUB>2</SUB> D and calciuric response, because calciuric responses in the steroid group were higher than the values expected from the elevations of serum calcium, as a result of an inhibition of renal tubular reabsorption of calcium by glucocorticoid. Plasma 1, 25 (OH) <SUB>2</SUB> D and calcemic response correlated negatively with the 3-month dosage of prednisolone (r=-0.516, p<0.05, r=-0.546, p<0.05, respectively). There was no correlation between plasma 1, 25 (OH) <SUB>2</SUB> D or calcemic response and nephrogenous cAMP in the steroid group, suggesting the coexistence of other factors, such as increased urinary calcium excretion,
- 日本内分泌学会の論文