Subcutaneous administration of the amino-terminal fragment of human parathyroid hormone-(1-34): kinetics and biochemical response in estrogenized osteoporotic patients

Abstract

A standard dose (400 U or 25 micrograms) of human (h) PTH-(1-34) was administered sc in 11 estrogen-treated patients with postmenopausal osteoporosis. Increments in circulating hPTH-(1-34) were brisk, peaking at 30 min, with variable peak levels averaging 10 times normal. Clearance of the peptide from the circulation followed an expontential pattern, with a mean t1/2 of 75 min. Peptide administration was followed by an immediate decline in serum concentrations of PTH-(1-84), which remained suppressed at about 65% of the basal value for the duration of the study (4 h). Serum calcium did not increase until 120 min, thus occurring after the diminution in PTH-(1-84). Serum phosphorus declined promptly as urinary phosphate excretion increased. There were no clear changes in urinary calcium excretion, but urinary cAMP excretion increased within 120 min. In 9 of 11 patients, the serum concentration of 1,25-dihydroxyvitamin D increased, with mean levels increasing progressively after 90 min to approximately 30% above baseline (P < 0.05). In conclusion, sc administration of 25 micrograms hPTH-(1-34) produces significant short term changes in mineral homeostasis that appear to be mediated by the kidney, parathyroid gland, and skeleton, with the latter displaying the most delayed response.