Improved assessment of bone turnover by the PTH-(1-84) large C-PTH fragments ratio in ESRD patients

Background. The "intact" parathyroid hormone (PTH) assay recognizes PTH-(1- 84) as well as amino terminally truncated PTH fragments. that is, large car boxyterminal PTH fragments (C-PTH fragments). The present study investigate d whether the use of the plasma PTH-(1-84)/C-PTH fragment ratio enhances th e noninvasive assessment of bone turnover in patients on dialysis. Methods. Bone biopsies and blood samples for determinations of routine indi ces of bone turnover and PTH peptides were obtained in 51 adult patients on dialysis not treated with drugs affecting bone such as vitamin D or cortic osteroids. Blood levels of large C-PTH fragments were calculated by subtrac ting PTH-(1-84) from "intact" PTH. Patients were classified according to th eir levels of bone turnover based on histomorphometrically obtained results of activation frequency. Prediction of bo c turnover by the various blood indices was done by using proper statistical methods. In addition, hypercal cemia was induced by calcium gluconate infusion in a subset of patients, an d levels of PTH-(1-84), "intact" PTH. and PTH(1-84)/C-PTH fragment ratio we re determined. Results. The PTH-(1-84)/C-PTH fragment ratio was the best predictor of bone turnover. A ratio >1 predicted high or normal bone turnover (sensitivity 1 00%), whereas a ratio <1 indicated a high probability (sensitivity 87.5%) o f low bone turnover. Calcium infusion resulted in decrease in PTH-(1-84)/C- PTH fragment ratio. Conclusions. The PTH-(1-84)/C-PTH fragment ratio predicts bone turnover wit h acceptable precision for biological measurements, Moreover. a change in s erum calcium levels is one of the regulators of the relative amount of circ ulating PTH(1-84) and its large C-PTH fragments.