TREATMENT OF SECONDARY HYPERPARATHYROIDISM WITH INTERMITTENT ORAL HIGH-DOSES OF 1-ALPHA-OHD3 PLUS PHARMACOLOGICAL DOSE OF 24,25(OH)(2)D-3

The present study examined the effect of intermittent opal high doses of 1-alpha OHD3 in combination with a pharmacological dose of 24,25(OH )(2)D-3 on parathyroid hormone (PTH) secretion. Twenty hemodialysis (H D) patients (10 males, aged 26-72 years, on regular hemodialysis for 7 -128 months) with secondary hyperparathyroidism resistant to long-term low-dose 1-alpha-OHD3 therapy were studied for 24 weeks. At the outse t of the study they were randomly divided into two groups: group 1 rec eived high-dose 1-alpha-OHD3 plus 24,25(OH)(2)D-3 (2 x 5 mu g/day) and group 2 was on monotherapy with 1-alpha-OHD3. 1-alpha-OHD) was given three times a week in the evening before each HD in gradually increase d doses from 1 to 4 mu g adjusted to keep serum calcium levels below 2 .6 mmol/L. During the therapy mean serum calcium and ionized calcium l evels increased but remained in the normal ranges without differences between the two groups. However, the frequency of hypercalcemia episod es was different in the two groups. In the first 12 weeks the number o f hypercalcemia episodes was significantly lower in group 1 than in gr oup 2 (6 vs. 12; p <.05), allowing the use of significantly higher 1-a lpha-OHD3 doses in group 1. In the second 12 weeks of the study the 1- alpha-OHD3 dose in group 1 had to be reduced due to more frequent appe arance of hypercalcemia. So, the 1-alpha-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 combine d therapy than in those of group 2 an monotherapy. After 4 weeks of th erapy mean plasma PTH levels were reduced by 48.9% in group 1 and by 2 8.5% 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 th at intermittent oral administration of high doses 1-alpha-OHD3 effecti vely reduced plasma PTH levels, but the appearance of hypercalcemia re quired close control of the patients. The addition of 24,25(OH)(2)D-3 increased efficacy and decreased the hypercalcemic effect of oral high doses of 1-alpha-OHD3, although this influence diminished during the therapy.