0 %), and second were skin and subcutaneous tissue disorders and laboratory test abnormalities (9 cases, 32.1 %). Hypercalcemia was not observed. Discussion This study aimed to clarify the PK, calcium metabolism, and profile of bone turnover markers (response at 24 h after injection and changes from baseline levels during 24 weeks) with once-weekly injections of 56.5 μg teriparatide for

24 weeks. We previously reported on the response for up to 14 days after a single injection of 56.5 μg teriparatide click here in healthy postmenopausal women [7], but whether this response was sustained for the long-term in women with osteoporosis was unknown. At data collection during the 24 week observation period, the changes in PK, calcium metabolism, and bone turnover markers at 24 h after injection repeatedly showed the same direction and level of response. It has been reported that, with PTH administration, PTH/PTHrP receptors are down-regulated, the receptor number decreases [8–10], and the receptor decrease is also regulated at the gene expression level [11, 12]. However, based on the results of the responses in the present study, even

if PTH/PTHrP receptors are transiently down-regulated by PTH administration, the response was repeatedly sustained with once-weekly injections of 56.5 μg teriparatide. This is the first evidence in humans that this website the response at 24 h after injection of teriparatide is repeated without attenuation during weekly administration. The transient decrease followed by an increase in bone

formation markers and the transient increase followed by a decrease in bone resorption markers at 24 h after injection of 56.5 μg teriparatide were repeated each time at the same levels for up to 24 weeks. PTH is reported to increase RANKL expression on osteoblast lineage cells and to trigger osteoclast differentiation and activation. Ma et al. reported that, 1 h after PTH administration in mice, RANKL increased and OPG decreased at the mRNA level, and after 3 h, they returned to baseline levels [13]. This response after teriparatide injection, in these which bone resorption increased transiently and then returned to basal levels after 24 h, was also confirmed in humans in the present study. Meanwhile, PTH in vitro has been reported to inhibit bone formation, such as collagen synthesis [14], osteocalcin production [15], and calcified bone-like nodule formation in primary osteoblast cultures [16]. However, Bellows and our group found that when PTH is removed from culture, the osteoblast function that was inhibited was restored [15, 16]. In addition, PTH stimulates the proliferation and differentiation of osteoprogenitor cells and pre-osteoblasts [15, 17], inhibits apoptosis [18, 19], and acts to gradually increase the osteoblast number. Based on these findings, the 24 h responses in osteocalcin and P1NP with injection of 56.