1. The influence of the time of the day of the administration of synthetic human parathyroid hormone fragment-(1-34) [hPTH-(1-34)] on its anabolic effect in bone was investigated in 23 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control morning, hPTH-(1-34)-treated morning, vehicle control afternoon and hPTH-(1-34)-treated afternoon, and once daily received a subcutaneous injection of 8 μg of hPTH-(1-34)/100 g body weight for 11 days. The increase in net intestinal calcium absorption and the increase in calcium balance were not influenced by the time of day of hPTH-(1-34) treatment. Four days after cessation of treatment, the net intestinal calcium absorption and calcium balance in hPTH-(1-34)-treated rats were not different from those of the control rats.
2. Modulation of the anabolic effect by variation of the hPTH-(1-34) dosage regimen was investigated in 43 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control, environmental control, 8 μg of hPTH-(1-34)/100 g body weight every 3 days for 24 days, 8 μg of hPTH-(1-34)/100g body weight every 2 days for 16 days, 8 μg of hPTH-(1-34)/100 g body weight every day for 8 days, 4 μg of hPTH-(1-34)/100 g body weight twice a day for 8 days and 2.7 μg of hPTH-(1-34)/100 g body weight three times a day for 8 days. In all cases, the total dose of hPTH-(1-34) received was 64 μg/100g body weight. Net intestinal calcium absorption and calcium balance increased significantly in the groups that received hPTH-(1-34) once a day, twice a day and three times a day. In relation with increased frequency of dosing, a significant linear trend existed for the increase in net intestinal calcium absorption and calcium balance. The hPTH-(1-34)-induced increase in total tibia calcium, total vertebrae calcium, tibia dry weight and vertebrae dry weight also tended to be more pronounced with more frequent dosing, although the trend was not significant.
3. Thus, smaller intervals between doses of hPTH-(1-34) enhance the anabolic response in bone despite the smaller doses. This effect may be secondary to 1,25-dihydroxyvitamin D3-induced increased intestinal calcium absorption, decreased 1,25-dihydroxyvitamin D3-induced bone resorption, up-regularion of osteoblast receptors for parathyroid hormone, or a combination of these three factors.