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 o f high-dose i.v. pulses of calcitriol (CLT) on hyperparathyroid bone d isease (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 Tl-201-Tc-99 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 pretrea tment value of PTH was 966 +/- 160 (mean +/- SE) pg/ml and it had decr eased significantly by the first week (T = 2.4, P < 0.04), and had fal len an average of 80% by the 35th week. Ionized plasma calcium concent ration 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, wh ile bGLA tended to increase immediately after the start of the therapy and to significantly decrease thereafter (T = 3.2; P < 0.01). There w ere significant decreases in all histomorphometric indices of HBD: the osteoid volume from 12 +/- 1.8 to 4.8 +/- 0.5% (P < 0.001), the osteo id surface from 45.7 +/- 3.2 to 27 +/- 5.2% (P < 0.001), the osteoblas tic 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 osteocla st surface from 2.2 +/- 0.3 to 2.2 +/- 0.3% (P < 0.009); there was eve n 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 i ntensity of (201)T1 uptake before therapy scored 7.8 (range 4 to 9.2) arbitrary visual units and decreased significantly (P < 0.001; Wilcoxo n test) to 0.4 (0 to 8.25) after eight months of CLT treatment, sugges ting significant decreases of the mass of the parathyroid glands. Thus , this study demonstrates that long-term therapy with high-dose i.v. p ulses of CLT in CHU with proven HBD is able to consistently decrease t heir circulating iPTH to levels comparable with those of subjects with mild or no HBD and also td decrease the functional mass of their para thyroid glands. Further studies will ascertain what dose of CLT is req uired to maintain this state of euparathyroidism once the hyperparathy roidism has been reversed.