PTH 1-84 and PTH "7-84" in the noninvasive diagnosis of renal bone disease

Background: The intact parathyroid hormone (PTH) assay evaluates levels of serum 1-84 PTH and other N-terminally truncated PTH fragments, mainly PTH "7-84." This PTH molecule has been found experimentally to interfere with biological activity of PTH 1-84, perhaps through its binding to the PTH receptor complex. Therefore, assuming that high levels of PTH 7-84 are a cause of bone resistance to PTH, it has been hypothesized that a decreased 1-84 to 7-84 PTH ratio caused by a relative increase in PTH 7-84 level might help in the noninvasive diagnosis of low-turnover osteodystrophy (LTO). Methods: This study was performed in 35 patients with chronic renal failure on hemodialysis therapy who underwent bone biopsy for a histological, histomorphometric, and histodynamic study. In addition, blood samples were obtained for intact PTH, 1-84 PTH, and total PTH assays. PTH 7-84 level was obtained from the difference between total and 1-84 PTH assay results. Results: Nine patients had LTO (8 patients, adynamic bone disease; 1 patient, osteomalacia),12 patients had hyperparathyroidism (HP), and 14 patients had mixed osteodystrophy (MO). On average, 1-84 PTH levels were approximately 60% of mean values for intact PTH. The two assays were strictly correlated. Average 1-84 to 7-84 PTH ratios were 1.57 +/- 0.85, 1.73 +/- 1.31, and 1.95 +/- 2.1 in the three histological groups (LTO, HP, and MO, respectively), with no significant difference. Conclusion: Contrary to previous expectations, results do not favor the hypothesis of a role of 7-84 PTH in bone resistance in renal osteodystrophy. The 1-84 to 7-84 PTH ratio is not a marker of LTO and is of no use in noninvasive histological diagnosis. (C) 2002 by the National Kidney Foundation, Inc.