Influence of the dosing frequency of parathyroid hormone-(1-38) on its anabolic effect in bone and on the balance of calcium, phosphorus and magnesium.

Abstract

The effect of the frequency of administration of synthetic human parathyroid hormone fragment 1-38 [hPTH-(1-38)] on bone formation and on the balance of calcium, phosphorus, and magnesium was investigated in 32 9-week-old female Sprague-Dawley rats, using a randomly complete block design. Rats received subcutaneously during 14 days either the vehicle solution once a day or 50 micrograms hPTH-(1-38)/kg BW once a day at 8:00 a.m., twice a day at 8:00 a.m. and 5:00 p.m. or three times a day at 8:00 a.m., 0:30 p.m., and 5:00 p.m. The balance study was performed during the last 48 h of the hPTH-(1-38) treatment schedule after which femora, tibiae, and lumbar vertebrae were removed for the determination of the dry weight, volume, and contents of Ca, P, Mg, hydroxyproline, and DNA. PTH treatment was associated with a significant increase of the apparent intestinal absorption of Ca, P, and Mg. Mean urinary Ca excretion augmented with the increase of the frequency of dosing. Urinary Ca excretion correlated negatively with the Ca apparent intestinal absorption and with the Ca content of the tibiae in the 2 groups with the highest frequency of dosing. The mean Ca, P, and Mg balances, the mean contents of bone Ca, P, and Mg and the mean bone dry weights were significantly increased with PTH treatment. In contrast to the mean volume of tibiae which was not affected by the PTH administration, the mean volume of the fifth lumbar vertebrae increased with the treatment. With the 2 times and 3 times daily treatments, mean hydroxyproline concentrations in the femora were significantly higher than the control values. An increase of the mean hydroxyproline content of the third lumbar vertebrae was evidenced with the 1 time and 2 times daily treatment, but the mean of the highest frequency of dosing was not different from that of the control group. The DNA content of femoral and of the fourth lumbar vertebrae significantly decreased with the frequency of dosing.