Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia

Abstract

To examine the possibility that uremia alters the relationship between bioactive PTH serum concentrations and its osseous end-organ response, we evaluated the relationship between circulating intact PTH and bone turnover in 39 end-stage renal disease patients with hyperparathyroid-mediated bone disease of varying severity. We excluded from analysis patients with coexistent defects in mineralization to insure that bone remodeling indices primarily reflected the effects of PTH. The distribution of serum PTH levels ranged from normal to markedly elevated. Regression analysis between circulating intact PTH concentrations, measured by a two-site immunoradiometric assay, and osseous indices of hyperparathyroidism, determined by quantitative bone histological analysis of iliac crest bone biopsies, showed that bioactive serum PTH levels correlated linearly with bone formation (r = 0.836), woven osteoid volume (r = 0.718), and marrow fibrosis (r = 0.856), and nonlinearly with parameters of bone resorption (r = 0.760). From these functional relationships, we found that the average serum intact PTH level of approximately 165 pg/mL, a value that exceeds the upper limit of intact PTH in nonuremic subjects (65 pg/mL) by 2.5-fold, defines the upper normal limit of bone turnover in uremic subjects. Indeed, the average serum PTH concentrations reached 500 pg/mL before histological evidence of severe hyperparathyroidism developed in uremic subjects. These findings demonstrate that elevated PTH concentrations are necessary to maintain normal bone remodeling in the uremic setting. Consequently, it may not be necessary to attain normal serum intact PTH levels to control the osseous manifestations of PTH excess in uremic subjects.