[A double blind trial of alfacalcidol on patients with rheumatoid arthritis (RA)]. Prevention of glucocorticoid-induced osteopenia: effect of oral 25-hydroxyvitamin D and calcium. Effects of large doses of calciferol on patients with rheumatoid arthritis. A double-blind clinical trial.
A double blind comparative trial was performed in order to study the efficacy and safety of alfacalcidol (1 alpha-OH-D3) in a total of 140 patients with RA admitted to 31 institutes, using a placebo as the control. The treatment period was 16 weeks. The doses of 1 alpha-OH-D3 were 1.0 microgram/day and 2.0 micrograms/day. It was permissible to use non-steroid anti-inflammatory drugs for basic treatment and oral steroidal preparations for maintenance treatment without changing the doses of these drugs during the study period in patients who had been treated with them before participating in the study (for oral steroidal preparations, the dose was limited to 5 mg/day or less as prednisolone). The percentage of patients with slight improvement was about 10% higher in 1 alpha-OH-D3 groups than in placebo group, but the difference between them was not significant. The results tended to be better in the treated groups than in the placebo group, but there was no significant difference between them with regard to duration of morning stiffness, number of joints with pain, number of joints with swelling and Lansbury's index. The effects of 1 alpha-OH-D3 on various immunological parameters including lymphocyte subsets were not clearly demonstrated. However, interestingly, the ratio of OKT-4/OKT-8 was found not to change in patients whose initial value was normal, while it tended to decrease after 1 alpha-OH-D3 treatment in patients whose initial value was abnormally high. The improvement of bone atrophy was judged by microdensitometry (MD) method using X-ray picture of hands. The indexes of bone density (GS max, GS min and sigma GS/D) demonstrated that 1 alpha-OH-D3 prevents reduction in bone density. 1 alpha-OH-D3 did not trigger hypercalcemia in any case. However there was a slight but significant increase of serum Ca value in the group with higher dose (2.0 micrograms/day). Taking the efficacy into consideration, the dose of 1.0 microgram/day was judged to be suitable for long-term treatment. Twenty-four patients (9 M and 15 F, age range 51-82) with polymyalgia rheumatica receiving 6-methylprednisolone for a period of 9 months (16 mg/daily/two weeks, 14 mg/daily/two weeks, 12 mg/daily/1 month, 10 mg/daily/1 month, 8 mg/daily/1 month, 6 mg/daily/1 month and 4 mg/daily for the last four months) were randomly assigned to receive either 250HD3 (35 mcg/day for 25 days/month) (Group A) or placebo (Group B) in a double-blind study. All patients also received 500 mg elemental calcium daily. Before and at 3, 6 and 9 months ESR, tenderness on palpation and subjective pain were evaluated. At the same times, mineral metabolism parameters (serum calcium, phosphorus, alkaline phosphatase, 24-h urinary calcium, phosphate and 24-h hydroxyproline excretion) and radial bone mineral content (BMC) were evaluated. Activity indexes (ESR and clinical parameters) improved in both groups. Furthermore, serum alkaline phosphatase and 24-h hydroxyproline excretion decreased significantly only in Group A, and BMC decreased significantly in Group B but rose slightly in Group A. No side effects were observed in any of the patients. nan