First Clinical Observations with hPTH(1-38), a More Potent Human Parathyroid Hormone Peptide

Abstract

Defective cleavage of PTH may be a factor in the genesis of osteoporosis (Atkinson, Vido, Keck and Hesch 1983). Normal cleavage of PTH takes place between amino acids 34-35 and 37-38 (Pillai, Botti and Zull 1983). To date all biological and clinical studies have concentrated on the shorter hPTH(l-34) cleavage product. However, HPLC analysis shows a longer peptide to be the major circulating form of amino-terminal bioactivity (Schettler, AufmKolk, Atkinson, Radeke, Enters and Hesch 1984). Such an extended peptide will have a greater beta sheet tertiary structure and hydrophobicity, suggesting higher biological activity. This was confirmed when we prepared and tested hPTH(l-38). In the human renal membrane and bone cell bioassays hPTH(l-38) had a greater biopotency than hPTH (1-34

Anabolic Actions of Parathyroid Hormone on Bone*

“…Hesch et al (229) investigated eight osteoporotic patients treated with hPTH(l-38) instead of hPTH(l-34) as early clinical observations had suggested that the former peptide had somewhat greater potency (230). The protocol was designed to take advantage of PTH as both an activator of skeletal remodeling (see section on ADFR below) as well as an anabolic agent.…”