Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure

Bone. 2003 Sep;33(3):372-9. doi: 10.1016/s8756-3282(03)00202-3.


Parathyroid hormone (PTH)(1-34), given once daily, increases bone mass in a variety of animal models and humans with osteoporosis. However, continuous PTH infusion has been shown to cause bone loss. To determine the pharmacokinetic profile of PTH(1-34) associated with anabolic and catabolic bone responses, PTH(1-34) pharmacokinetic and serum biochemical profiles were evaluated in young male rats using dosing regimens that resulted in either gain or loss of bone mass. Once-daily PTH(1-34) or 6 PTH(1-34) injections within 1 h, for a total daily dose of 80 microg/kg, induced equivalent increases in proximal tibia bone mass. In contrast, 6 PTH(1-34) injections/day over 6 h for a total dose of 80 microg/kg/day or 3 injections/day over 8 h for a total of 240 microg/kg/day decreased tibia bone mass. The PTH(1-34) pharmacokinetics of the different treatment regimens were distinctive. The magnitude of the maximum serum concentrations (Cmax) of PTH(1-34) and area under the curve (AUC) did not predict the catabolic bone outcome. Compared to the anabolic pharmacokinetic profile of a transient increase in PTH(1-34) with rapid decreases in serum calcium and phosphate, the catabolic regimen was associated with PTH(1-34) concentrations remaining above baseline values during the entire 6-h dosing period with a trend toward an increase in serum calcium and a prolonged decrease in phosphate. The pharmacokinetic profiles suggest that the anabolic or catabolic response of bone to PTH(1-34) is determined primarily by the length of time each day that serum concentrations of PTH(1-34) remain above baseline levels of endogenous PTH and only secondarily by the Cmax or AUC of PTH(1-34) achieved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Remodeling / drug effects*
  • Calcium / blood
  • Dose-Response Relationship, Drug
  • Humans
  • Injections, Subcutaneous
  • Male
  • Parathyroid Hormone / pharmacology*
  • Peptide Fragments / pharmacology*
  • Phosphates / blood
  • Rats
  • Rats, Sprague-Dawley
  • Tibia / drug effects*
  • Tibia / metabolism*


  • Parathyroid Hormone
  • Peptide Fragments
  • Phosphates
  • Calcium