First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl

Background. First-generation immunometric assays for "intact" parathyroid hormone (iPTH) also measure large N-terminally truncated PTH fragments, whereas second-generation assays, such as the "bio-intact" PTH (biPTH) assay, measure only full-length biologically active PTH(1-84). This study compared iPTH and biPTH assays during cinacalcet treatment in subjects with secondary HPT receiving dialysis. Methods. Four hundred and ten subjects were enrolled in a 26-week randomized, double-blind, placebo-controlled trial of oral cinacalcet (or placebo), 30 to 180 mg once daily, and efficacy was assessed using biPTH and iPTH assays. Results. Compared with control treatment, cinacalcet improved the management of secondary HPT. Both biPTH and iPTH decreased by 38% ± 3% during weeks 13 to 26 in the cinacalcet group; biPTH increased by 23% ± 4% and iPTH increased by 9.5% ± 3% in the control group (P < 0.001). Fifty-six percent of cinacalcet subjects and 10% of control subjects had a ≥30% reduction in biPTH, and 61% and 11%, respectively, had a ≥30% reduction in iPTH. Significant correlations between biPTH and iPTH levels were observed throughout the study. Both assays correlated similarly with bone-specific alkaline phosphatase levels. The ratio of biPTH to iPTH was maintained at 56% ± 1% after treatment in both treatment groups. Increasing serum calcium levels were associated with a decreasing ratio of biPTH to (iPTH-biPTH). Conclusion. These data show that PTH can be monitored with either iPTH or biPTH assays during therapy with cinacalcet, and that cinacalcet therapy does not exert a major influence on the ratio between PTH(1-84) and large, N-terminally truncated PTH fragments.