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

• Published in: Bone (New York, N.Y.) Vol. 33; no. 3; pp. 372 - 379
• Main Authors: Frolik, Charles A, Black, Elwood C, Cain, Ricky L, Satterwhite, Julie H, Brown-Augsburger, Patricia L, Sato, Masahiko, Hock, Janet M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2003; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Bone Remodeling - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Calcium - blood; Dose-Response Relationship, Drug; Humans; Injections, Subcutaneous; Male; Medical sciences; Parathyroid Hormone - pharmacology; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Phosphates - blood; Rats; Rats, Sprague-Dawley; Tibia - drug effects; Tibia - metabolism; Biochemical analysis; Rat; Rodentia; Concentration; Experimental study; Biological activity; Protein hormone; Parathormone; Vertebrata; Mammalia; Treatment; Parathyroid hormone; Tibia; Animal; Hormonal regulation; Serum; Catabolism; Bone; Anabolic agent; Pharmacokinetics
• ISSN: 8756-3282; 1873-2763
• 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 μg/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 μg/kg/day or 3 injections/day over 8 h for a total of 240 μg/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 ( C max) 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 C max or AUC of PTH(1-34) achieved.