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Renal bone disease or renal osteodystrophy is the term used to describe the spectrum of histologic abnormalities encountered in patients with chronic kidney disease (CKD). The patterns of bone histology encountered in the setting of CKD range from states of high bone turnover, such as osteitis fibrosa, the result of hyperparathyroidism, to states of abnormally low bone turnover, such as adynamic bone.1 The major factors involved in the pathogenesis of secondary hyperparathyroidism include phosphate retention as glomerular filtration rate decreases and low levels of calcitriol as renal mass is reduced. Both of these factors may lower serum calcium and therefore stimulate parathyroid hormone (PTH) secretion. In addition to these indirect effects, low levels of calcitriol and high serum phosphorus have been shown to have direct effects on the parathyroid gland to increase PTH secretion. The pathogenetic factors involved in the development of adynamic bone disease are less well understood, but it appears that oversuppression of PTH and the use of vitamin D compounds may play a role. Thus, in the management of renal osteodystrophy, it is important to be able to monitor and treat hyperparathyroidism effectively while at the same time avoiding oversuppression of PTH. In this regard, accurate measurements of circulating PTH levels are an essential guide in the management of renal bone disease. It is well accepted that PTH is present in the circulation in the form of both the intact 84-amino acid peptide and a variety of truncated fragments.2–4 Although the role of the intact PTH molecule as a major regulator of mineral ion homeostasis is well established, the actions of PTH fragments have remained poorly understood. In this review, we discuss the generation of PTH metabolites and the evidence supporting their biologic activity and their potential role in renal bone disease.

Accurate measurements of parathyroid hormone (PTH) in plasma are necessary for the assessment, monitoring, and therapy of disorders of bone and mineral metabolism including renal osteodystrophy. Assays for PTH have evolved to provide 2-site immunometric assays that are highly specific for the intact 84 amino-acid peptide, PTH (1-84). With the advent of such assays, it has been shown that the prior generation of assays, thought to measure intact PTH, in fact, also detected a PTH peptide that was truncated at the N-terminus and that appeared to be similar to PTH (7-84). There has been renewed interest in such circulating PTH fragments in view of the demonstration that PTH (7-84) (and other PTH peptides) might have biologic effects. These effects include an action to oppose the calcemic effect of PTH in vivo and to inhibit bone resorption and osteoclast generation in vitro. These effects appear to be mediated by actions of a receptor for PTH peptides with specificity for the C-terminal region of PTH and distinct from the PTH receptor known to be responsible for all of the classic actions of PTH. Although the C-PTH receptor has not yet been cloned, the observations have opened a new field of research in parathyroid physiology. Clinical applications of the assay of such PTH fragments in relation to the amount of circulating PTH (1-84) concentrations are being sought actively as the new PTH assay methodology is applied to the clinical arena and as the biology of the C-PTH receptor and C-terminal PTH fragments are investigated.