New lessons from old assays: parathyroid hormone (PTH), its receptors, and the potential biological relevance of PTH fragments.

Accurate and reliable measurements of the concentration of parathyroid hormone (PTH) in serum or plasma are necessary for the diagnostic assessment of various clinical disorders of bone and mineral metabolism [1,2]. In patients with chronic renal failure, serum or plasma PTH levels are commonly used to identify different subtypes of renal osteodystrophy and to monitor evolution of the disorder [3–10]. Largely for practical reasons, plasma PTH levels serve as surrogates for bone histology in patients with end-stage renal disease (ESRD), and they are an essential guide to ongoing clinical management, particularly during the treatment of secondary hyperparathyroidism with vitamin D sterols [11–13]. It is now generally recognized that the several PTH assays that have been employed widely for many years do not measure exclusively the full-length biologically active hormone comprised of 84 amino acids, or PTH(1–84) [14–16]. Rather, these assays also detect large N-terminally truncated, PTH fragments that are present in plasma not only in patients with chronic renal failure but also in those with normal renal function [15,16]. Recent experimental evidence suggests that some of these peptides have biological actions in bone that are distinct from those traditionally ascribed to PTH(1–84) [17,18]. Such findings have important implications for the diagnosis and clinical management of patients with renal bone disease in particular and for understanding bone biology in general.