Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol

Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. The aim of this study was to assess the effect of a long-term course of high-dose i.v. pulses of calcitriol (CLT) on hyperparathyroid bone disease (HBD) and functional mass of parathyroid glands of chronically hemodialyzed uremic (CHU) patients. We prospectively studied nine CHU patients treated with CLT, 30 ng/kg/body wt, i.v., thrice weekly over a period of eight months. Plasma concentrations of intact parathyroid hormone (iPTH), bone GLA protein (bGLA) and bone isoenzyme of alkaline phosphatase (biALP) were sampled throughout. Transiliac bone biopsies were made before and after the start of CLT therapy. Double scanning scintigraphy of the neck with 201Tl-99Tc was made before, during and eight months after the start of the treatment. All patients but one, who later responded to higher than planned CLT doses, had significant decreases of plasma iPTH (F = 76; P < 0.0001; ANOVA). The mean pretreatment value of PTH was 966 ±160 (mean ± SE) pg/ml and it had decreased significantly by the first week (T = 2.4, P < 0.04), and had fallen an average of 80% by the 35th week. Ionized plasma calcium concentration was 1.19 ± .01 mmol/liter which rose significantly (F = 13.5; P < 0.0001) by the 14th week to maximal peak levels, averaging 1.34 ± .02 mmol/liter. Changes in biALP were parallel to those of iPTH, while bGLA tended to increase immediately after the start of the therapy and to significantly decrease thereafter (T = 3.2; P < 0.01). There were significant decreases in all histomorphometric indices of HBD: the osteoid volume from 12 ± 1.8 to 4.8 ± 0.5% (P < 0.001), the osteoid surface from 45.7 ± 3.2 to 27 ± 5.2% (P < 0.001), the osteoblastic surface from 11.8 ± 1.7 to 4.8 ± 1.08% (P < 0.001), the eroded surface from 6.6 ± 1.2 to 4.3 ± 0.9 (P < 0.002), and the osteoclast surface from 2.2 ± 0.3 to 1.2 ± 0.3% (P < 0.009); there was even renormalization in some individual patients. The bone formation rate was measured in six of the nine patients and was found to be lowered in all subjects who had had significant PTH decreases. The median of intensity of 201Tl uptake before therapy scored 7.8 (range 4 to 9.2) arbitrary visual units and decreased significantly (P < 0.001; Wilcoxon test) to 0.4 (0 to 8.25) after eight months of CLT treatment, suggesting significant decreases of the mass of the parathyroid glands. Thus, this study demonstrates that long-term therapy with high-dose i.v. pulses of CLT in CHU with proven HBD is able to consistently decrease their circulating iPTH to levels comparable with those of subjects with mild or no HBD and also to decrease the functional mass of their parathyroid glands. Further studies will ascertain what dose of CLT is required to maintain this state of euparathyroidism once the hyperparathyroidism has been reversed