Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy

Reliable measurements of parathyroid hormone (PTH) concentrations in serum or plasma are critical for the appropriate diagnosis and management of patients with renal osteodystrophy. With the introduction of second generation immunometric assays for PTH, it is now possible to measure exclusively full-length, biologically active PTH(1-84). In contrast, first generation immunometric assays that have been used widely for many years detect not only PTH(1-84), but also other large amino-terminally-truncated, PTH-derived peptides. This development will require a careful re-evaluation of PTH measurements, as determined by either first or second generation immunometric assays, and their relationship to bone histology and bone remodeling rates in patients with end-stage renal disease (ESRD). Such information is essential for proper clinical management, but only limited bone biopsy data are available to guide the interpretation of PTH results using second generation PTH assays. The different performance characteristics of first and second generation immunometic PTH assays also makes it possible to quantify the plasma levels of amino-terminally-truncated, PTH-derived peptides, which may accumulate disproportionately in patients with ESRD. Recent experimental evidence indicates that one or more of these peptides can modify bone cell activity and skeletal remodeling, possibly by interacting with a PTH receptor distinct from the type I PTH receptor that binds to the amino-terminal portion of PTH and mediates the classical biological actions of the hormone. The putative C-PTH receptor interacts with mid- and/or carboxyterminal regions of PTH and other amino-terminally-truncated PTH-derived peptides; signaling through it may contribute to the skeletal resistance to PTH that characterizes ESRD. The current review discusses certain aspects of the molecular structure of PTH and its interaction with various receptors, briefly comments about selected components of PTH secretion, highlights recent technical advances in PTH assays, and summarizes the effects of various PTH-derived peptides on bone cells and on skeletal metabolism.