title: Early Effects of Single and Low-Frequency Repeated Administration of Teriparatide, hPTH(1-34), on Bone Formation and Resorption in Ovariectomized Rats.
abstract: Intermittent repeated administration of teriparatide (TPTD) has potent anabolic effects on bones in vivo. However, TPTD has both anabolic and catabolic effects on osteoblasts in vitro, and the mechanisms underlying its promotion of bone formation are unclear. This study aimed to elucidate the time-dependent changes in bone formation and resorption by examining changes in bone turnover markers and bone tissue over time after TPTD administration with low frequency in ovariectomized rats. The amount of serum osteocalcin, a bone formation marker, was transiently reduced after single TPTD administration, but increased thereafter, remaining increased for several days. In contrast, the amount of excreted urinary C-telopeptide, a bone resorption marker, increased transiently after single TPTD administration, and subsequently returned to control levels on the day after administration. Tissue histomorphometric analyses conducted 8 h after administration showed no changes in bone formation or bone resorption parameters. However, at 48 h, the bone formation parameters OS/BS and Ob.S/BS were increased, while the bone resorption parameter ES/BS was decreased. After repeated TPTD administration for 4 weeks, OS/BS, Ob.S/BS, and MS/BS increased, while Oc.S/BS decreased. Serum osteocalcin at 4 weeks after repeated administration was significantly correlated with OS/BS and Ob.S/BS. These present findings indicate that TPTD has dual, time-dependent effects on bone resorption and bone formation. Immediately after single administration, there was transient promotion of bone resorption and suppression of bone formation. However, sustained stimulation of bone formation occurred thereafter. Furthermore, these data suggest that this sustained bone formation led to anabolic effects with repeated TPTD administration.
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan. isogai.yb@om.asahi-kasei.co.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Isogai
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takao-Kawabata
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Takakura
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Emika
authors.initials: E
authors.lastname: Sugimoto
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakazono
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ikegaki
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuriyama
authors.affiliation: Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka, 410-2321, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ishizuya
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000008:administration & dosage*
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide
keywords: Bone formation; Bone resorption; Bone turnover marker; Histomorphometry; Teriparatide