Treatment of Secondary Hyperparathyroidism with Intermittent Oral High Doses of 1-α-OHD₃ Plus Pharmacological Dose of 24,25(OH)₂D₃

Abstract

The present study examined the effect of intermittent oral high doses of 1-α-OHD₃ in combination with a pharmacological dose of 24,25(OH)₂D₃ on parathyroid hormone (PTH) secretion. Twenty hemodialysis (HD) patients (10 males, aged 26—72 years, on regular hemodialysis for 7—128 months) with secondary hyperparathyroidism resistant to long-term low-dose 1-α-OHD₃ therapy were studied for 24 weeks. At the outset of the study they were randomly divided into two groups: group I received high-dose 1-α-OHD₃ plus 24,25(OH)₂D₃ (2 × 5 µg/day) and group 2 was on monotherapy with 1-α-OHD₃ 1-α-OHD, was given three times a week in the evening before each HD in gradually increased doses from 1 to 4 µg adjusted to keep serum calcium levels below 2.6 mmol/L. During the therapy mean serum calcium and ionized calcium levels increased but remained in the normal ranges without differences between the two groups. However, the frequency of hypercalcemia episodes was different in the two groups. In the first 12 weeks the number of hypercalcemia episodes was significantly lower in group I than in group 2 (6 vs. 12; p <. 05), allowing the use of significantly higher 1-α-OHD₃ doses in group 1. In the second 12 weeks of the study the 1-α-OHD₃ dose in group I had to be reduced due to more frequent appearance of hypercalcemia. So, the 1-α-OHD₃ doses became similar in the two groups during the second 12 weeks of the study. The reduction of PTH plasma levels was more marked in patients in group 1 on combined therapy than in those of group 2 on monotherapy. After 4 weeks of therapy mean plasma PTH levels were reduced by 48.9% in group 1 and by 28.5% in group 2, and at the end of the study by a further 22.9% and 8.9% in groups 1 and 2, respectively. The results presented suggested that intermittent oral administration of high doses 1-α-OHD₃ effectively reduced plasma PTH levels, but the appearance of hypercalcemia required close control of the patients. The addition of 24,25-(OH)₂D₃ increased efficacy and decreased the hypercalcemic effect of oral high doses of 1-α-OHD₃, although this influence diminished during the therapy.