In 1998, the research group led by Pierre D’Amour (University of Montreal) demonstrated that the intact PTH (iPTH) assay measures both 1-84 PTH and 7-84 PTH. In that same year, Cantor, et al. (antibody producer for iPTH assays) produced the first specific Whole 1-84 PTH (CAP™) Assay. Consequent study of the biological importance of 7-84 PTH yielded several discoveries such as: 7-84 PTH circulates in the blood of normals and patients with a range of 10:1 to 1:10 compared to 1-84 PTH; it is produced in the parathyroid glands and has a half life twice as long as 1-84 PTH; it is hypocalcemic, inhibits formation of osteoclasts, osteoblasts and bone resorption; has its own C-terminal receptor and physically binds to bone cells; it down regulates the PTH1/PTHrp receptor; lowers bone turnover and can cause adynamic bone disease (ABD); its levels are regulated by blood calcium; inhibit the secretion of 1-84 PTH and increase more rapidly than 1-84 PTH with decreasing kidney function; 7-84 PTH helps to predict bone status in ESRD and is 94% accurate in predicting bone status in the 1-84 PTH/7-84 PTH ratio (critical to forming treatment plans for African Americans); 7-84 PTH increases are associated with growth retardation in pediatric ESRD patients and affect the mortality rate of hemodialysis patients. The concentration variability and biological actions of 7-84 PTH explain why the iPTH assay is non-diagnostic of bone disease, may not reliably guide therapy, and explain Block, et al.’s findings that elevated iPTH indicates the lowest mortality risk.
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