These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

This preliminary study was undertaken to investigate the efficacy of high-dose iv methylprednisolone pulse therapy in 5 patients with Graves' ophthalmopathy. One gram of methylprednisolone sodium succinate was given iv daily for 3 successive days. The 3-day infusion was repeated 3 to 7 times at intervals of 1 week; total duration of pulse therapy was 3 to 7 weeks. The clinical improvement of eye involvements by pulse therapy was assessed immediately after the last pulse therapy. The clinical assessment of the effect of pulse therapy for Graves' ophthalmopathy showed a good response in 3 patients, a fair response in one, and no response in one. However, in one patient, who was judged to show no response, complete improvement of the enlarged extraocular muscle was observed on orbital computed tomography. Moreover, two patients, who have been followed without any other therapies, showed no relapse of eye involvements for 32 and 10 months, respectively. Although it is impossible to determine whether pulse therapy is more effective than other immunosuppressive therapies, the results of this preliminary study suggest that pulse therapy may be a good immunosuppressive therapy for Graves' ophthalmopathy too. Controlled studies are desired.

Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.

To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis, an open-label, prospective, calcium-controlled study was conducted. A total of 80 patients with osteoporosis were divided into two groups: the control group, group C (mean age, 78.0 years), in which patients were given calcium, and group D (mean age, 77.4 years), in which the patients were given alfacalcidol 1 micro g/day together with calcium for 6 months. Calcium regulation, lumbar bone mineral density (LBMD), and markers for bone turnover were assessed. A significant increase in urinary calcium/creatinine ratio (90% increase from baseline at 3 months; P = 0.0083, and 60% at 6 months; P = 0.0091) and a significant decrease in serum parathyroid hormone (30% decrease from baseline at 6 months; P < 0.0001) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers (deoxypyridinoline and N-telopeptide) at 6 months (about 15% decrease from the baseline values) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers (bone-derived alkaline phosphatase and osteocalcin) in group D were significantly different at 6 months (-21.5%; P = 0.0047 and -13.4%; P = 0.0032, respectively) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values, suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates. The LBMD in group D increased by 1.7% and that in group C decreased by 1.6% ( P = 0.0384). The changes in calcium metabolism and LBMD were in good agreement with those in previous reports. Although the changes in bone turnover markers in group D were slight, significant reduction in bone turnover with alfacalcidol treatment, together with the change in calcium metabolism, may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously. In conclusion, alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis, and it may have beneficial effects on bone.

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