Anabolic action of teriparatide to osteoporotic patients

Abstract

Intermittent administration of human parathyroid hormone (PTH) [1-34], or teriparatide, has been used for osteoporotic treatment, which is available for daily and weekly administration for the osteoporotic patients in Japan, increasing bone mass and reduce bone fracture risk. In general, continuous PTH infusion shows catabolic effects in bone, while the intermittent administration of PTH results in anabolic action in osteoporotic patients. Intermittent PTH administration promotes preosteoblastic proliferation, as well as stimulates osteoblastic bone formation dependent on cell coupling with osteoclasts. Dosing frequency of PTH administration may affect resultant bone mass, and therefore, we have examined the anabolic effects of the high and low frequency of PTH administration using a mouse model. As a consequence, the high frequency of PTH administration accelerated the preosteoblastic proliferation with forming thick preosteoblastic network, osteoclastogenesis inside the preosteoblastic network, as well as osteoblastic bone formation. In contrast, the low frequency of PTH administration promoted osteoblastic bone formation, but, did not stimulate preosteoblastic proliferation and osteoclastogenesis. In addition, the high or low frequency of PTH administration demonstrated bone formation by manners of accelerated bone remodeling or bone remodeling/mini-modeling, respectively. Thus, the different dosing frequency of PTH administration may induce the different cellular mechanism of anabolic effects in bone.