Three-times-weekly administration of teriparatide improves vertebral and peripheral bone density, microarchitecture, and mechanical properties without accelerating bone resorption in ovariectomized rats.
Daily and weekly administration of teriparatide (PTH1-34) reduces the risk of osteoporotic bone fractures. However, their effects on markers of bone formation and bone resorption differ. These results indicate that the dosing frequency of teriparatide may affect bone metabolism and bone structure, with different effects on bone strength. In the present study, to evaluate the dose-related effects of a low administration frequency of teriparatide on bone status, we investigated the effects of three-times-weekly administration of teriparatide (1.1, 5.6, or 28.2 µg/kg) for 12 months on bone parameters, including bone metabolism markers, bone mineral density (BMD), micro-computed tomography, and bone strength, using 6-month-old ovariectomized (OVX) rats. Three-times-weekly administration of teriparatide dose-dependently increased the BMD of the lumbar vertebra and femur in OVX rats, and increased serum osteocalcin (a marker of bone formation), but not type I collagen C-telopeptide (a marker of bone resorption). The trabecular number and thickness increased in the vertebrae and femur, as in prior reports of daily teriparatide administration in OVX rats. Cortical thickness increased only toward the endocortical side of the femur, unlike with daily administration. Bone strength of the vertebrae and proximal and shaft of the femur was correlated with the changes in BMD and bone structure. These results demonstrate the effects of low frequency, intermittent administration of teriparatide on the biomechanical, and microstructural properties of bone in OVX rats.
Laboratory for Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka, 410-2321, Japan, takao.rb@om.asahi-kasei.co.jp.
Ryoko
R
Takao-Kawabata
Yukihiro
Y
Isogai
Aya
A
Takakura
Yukari
Y
Shimazu
Emika
E
Sugimoto
Osamu
O
Nakazono
Ichiro
I
Ikegaki
Hiroshi
H
Kuriyama
Shinya
S
Tanaka
Hiromi
H
Oda
Toshinori
T
Ishizuya
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000187:drug effects; D019379:Teriparatide / Q000494:pharmacology*; D055114:X-Ray Microtomography
D050071:Bone Density Conservation Agents; D019379:Teriparatide